Difference between revisions of "Breast cancer, HER2-positive"
Warner-admin (talk | contribs) m (Text replacement - "color:#00cd00"|Seems to have" to "color:#a1d99b"|Seems to have") |
m |
||
(763 intermediate revisions by 5 users not shown) | |||
Line 1: | Line 1: | ||
− | + | <span id="BackToTop"></span> | |
− | + | <div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px"> | |
− | + | [[#top|Back to Top]] | |
− | + | </div> | |
− | '''< | + | {{#lst:Editorial board transclusions|breast}} |
− | + | ''Are you looking for a regimen, but can't find it here? It is possible that we've moved it to the [[Breast_cancer,_HER2-positive_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Breast_cancer,_HER2-positive_-_null_regimens|this page]]. If you still can't find it, please let us know so we can add it!'' | |
+ | <br>'''Note: these are regimens tested in biomarker-specific populations, please see the [[breast cancer|main breast cancer page]] for other regimens.''' | ||
+ | *Regimens for [[Breast cancer, ER and HER2 co-expressing|'''ER/HER2 co-expressing ("double positive") breast cancer are here''']]. | ||
+ | *Regimens for [[Breast cancer, CNS metastases|'''CNS metastases are here''']]. | ||
{| class="wikitable" style="float:right; margin-right: 5px;" | {| class="wikitable" style="float:right; margin-right: 5px;" | ||
|- | |- | ||
− | |<div style="background-color: # | + | |<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div> |
− | <div style="background-color: # | + | <div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div> |
|} | |} | ||
{{TOC limit|limit=3}} | {{TOC limit|limit=3}} | ||
+ | =Guidelines= | ||
+ | '''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.''' | ||
+ | ==[https://www.asco.org/ ASCO]== | ||
+ | *'''2022:''' Ramakrishna et al. [https://doi.org/10.1200/JCO.22.00520 Management of Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases] [https://pubmed.ncbi.nlm.nih.gov/35640075/ PubMed] | ||
+ | **'''2018:''' Ramakrishna et al. [https://doi.org/10.1200/JCO.2018.79.2713 Recommendations on disease management for patients with advanced human epidermal growth factor receptor 2-positive breast cancer and brain metastases: American Society of Clinical Oncology clinical practice guideline update] [https://pubmed.ncbi.nlm.nih.gov/29939840/ PubMed] | ||
+ | **'''2014:''' Ramakrishna et al. [https://doi.org/10.1200/JCO.2013.54.0955 Recommendations on disease management for patients with advanced human epidermal growth factor receptor 2-positive breast cancer and brain metastases: American Society of Clinical Oncology clinical practice guideline] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366342/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24799487/ PubMed] | ||
+ | *'''2022:''' Giordano et al. [https://doi.org/10.1200/JCO.22.00519 Systemic Therapy for Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer] [https://pubmed.ncbi.nlm.nih.gov/35640077/ PubMed] | ||
+ | **'''2018:''' Giordano et al. [https://doi.org/10.1200/JCO.2018.79.2697 Systemic therapy for patients with advanced human epidermal growth factor receptor 2–positive breast cancer: ASCO Clinical Practice Guideline update] [https://pubmed.ncbi.nlm.nih.gov/29939838/ PubMed] | ||
+ | **'''2014:''' Giordano et al. [https://doi.org/10.1200/JCO.2013.54.0948 Systemic therapy for patients with advanced human epidermal growth factor receptor 2-positive breast cancer: American Society of Clinical Oncology clinical practice guideline] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6076031/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24799465/ PubMed] | ||
+ | *'''2021:''' Korde et al. [https://doi.org/10.1200/jco.20.03399 Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer: ASCO Guideline] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274745/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33507815/ PubMed] | ||
+ | *'''2020:''' Denduluri et al. [https://doi.org/10.1200/jco.20.02510 Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer: ASCO Guideline Update] [https://pubmed.ncbi.nlm.nih.gov/33079579/ PubMed] | ||
+ | **'''2018:''' Denduluri et al. [https://doi.org/10.1200/JCO.2018.78.8604 Selection of optimal adjuvant chemotherapy and targeted therapy for early breast cancer: ASCO clinical practice guideline focused update] [https://pubmed.ncbi.nlm.nih.gov/29787356/ PubMed] | ||
+ | **'''2016:''' Harris et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933134/ Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: American Society of Clinical Oncology Clinical Practice Guideline] [https://pubmed.ncbi.nlm.nih.gov/26858339/ PubMed] | ||
+ | *'''2015:''' Van Poznak et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478102/ Use of biomarkers to guide decisions on systemic therapy for women with metastatic breast cancer: American Society of Clinical Oncology Clinical Practice Guideline] [https://pubmed.ncbi.nlm.nih.gov/26195705/ PubMed] | ||
+ | |||
+ | ==ASCO/CAP== | ||
+ | *'''2023:''' Wolff et al. [https://doi.org/10.1200/jco.22.02864 Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: ASCO–College of American Pathologists Guideline Update] [https://pubmed.ncbi.nlm.nih.gov/37284804/ PubMed] | ||
+ | **'''2014:''' Wolff et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4086638/ Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update] [https://pubmed.ncbi.nlm.nih.gov/24099077/ PubMed] | ||
+ | **'''2013:''' Wolff et al. [https://doi.org/10.1200/jco.2013.50.9984 Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update] [https://pubmed.ncbi.nlm.nih.gov/24101045/ PubMed] | ||
+ | **'''2007:''' Wolff et al. [https://doi.org/10.5858/2007-131-18-asocco American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer] [https://pubmed.ncbi.nlm.nih.gov/19548375/ PubMed] | ||
+ | |||
+ | ==[https://www.esmo.org/ ESMO]== | ||
+ | *'''2023:''' Tarantino et al. [https://doi.org/10.1016/j.annonc.2023.05.008 ESMO expert consensus statements (ECS) on the definition, diagnosis, and management of HER2-low breast cancer] [https://pubmed.ncbi.nlm.nih.gov/37269905/ PubMed] | ||
+ | *'''2017:''' Cardoso et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378224/ 3rd ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3).] [https://pubmed.ncbi.nlm.nih.gov/28177437/ PubMed] | ||
+ | *'''2015:''' Senkus et al. [https://doi.org/10.1093/annonc/mdv298 Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.] [https://pubmed.ncbi.nlm.nih.gov/26314782/ PubMed] | ||
− | |||
− | |||
− | |||
− | |||
− | |||
==NCCN== | ==NCCN== | ||
− | *[https://www.nccn.org/ | + | *''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1419 NCCN Guidelines - Breast Cancer].'' |
− | = | + | == St Gallen Breast Guidelines == |
+ | *'''2019:''' Burstein et al. [https://doi.org/10.1093/annonc/mdz235 Estimating the benefits of therapy for early-stage breast cancer: the St. Gallen International Consensus Guidelines for the primary therapy of early breast cancer 2019] [https://pubmed.ncbi.nlm.nih.gov/31373601 PubMed] | ||
− | + | *'''2017:''' Curigliano et al. [https://doi.org/10.1093/annonc/mdx308 St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2017] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6246241/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28838210 PubMed] | |
− | + | *'''2015:''' Coates et al. [https://doi.org/10.1093/annonc/mdv221 Tailoring therapies—improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4511219/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25939896 PubMed] | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
+ | =Neoadjuvant therapy, sequential regimens= | ||
+ | ==AC-TH (Paclitaxel) {{#subobject:gjac91|Regimen=1}}== | ||
+ | AC-TH: '''<u>A</u>'''driamycin (Doxorubicin) and '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axol (Paclitaxel) & '''<u>H</u>'''erceptin (Trastuzumab) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:b18877|Variant=1}}=== | ===Regimen {{#subobject:b18877|Variant=1}}=== | ||
− | {| | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | | | + | !style="width: 20%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Dates of enrollment |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |rowspan=2|[ | + | |rowspan=2|[https://doi.org/10.1016/S1470-2045(13)70411-X Robidoux et al. 2013 (NSABP B-41)] |
− | |rowspan=2 style="background-color:# | + | |rowspan=2|2007-2011 |
− | |AC - | + | |rowspan=2 style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |1. [[#AC-THL_.28Paclitaxel.29|AC-THL]] |
+ | |style="background-color:#fee08b"|Might have inferior pCR rate | ||
|- | |- | ||
− | |AC - | + | |2. [[#AC-TL_.28Paclitaxel.29|AC-TL]] |
− | |style="background-color:# | + | |style="background-color:#ffffbf"|Did not meet primary endpoint of pCR rate |
|- | |- | ||
|} | |} | ||
− | ====Chemotherapy, AC portion==== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
+ | ====Chemotherapy, AC portion (cycles 1 to 4)==== | ||
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Chemotherapy, TH portion (cycles 5 to 8)==== | |
− | |||
− | |||
− | ====Chemotherapy, TH portion==== | ||
*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | ||
+ | ====Targeted therapy, TH portion (cycles 5 to 8)==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22 |
− | **Cycles | + | **Cycles 6 to 8: 2 mg/kg IV once per day on days 1, 8, 15, 22 |
− | + | '''21-day cycle for 4 cycles, then 28-day cycle for 4 cycles (AC x 4; TH x 4)''' | |
− | '''28-day cycle for 4 cycles | + | </div> |
− | + | <div class="toccolours" style="background-color:#cbd5e7"> | |
− | + | ====Subsequent treatment==== | |
− | + | *[[Surgery#Breast_cancer_surgery|Surgery]], then adjuvant [[#Trastuzumab_monotherapy_2|trastuzumab]] for a total of 52 weeks of therapy.'' | |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Robidoux A, Tang G, Rastogi P, Geyer CE Jr, Azar CA, Atkins JN, Fehrenbacher L, Bear HD, Baez-Diaz L, Sarwar S, Margolese RG, Farrar WB, Brufsky AM, Shibata HR, Bandos H, Paik S, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1183-92. Epub 2013 Oct 4. [ | + | # '''NSABP B-41:''' Robidoux A, Tang G, Rastogi P, Geyer CE Jr, Azar CA, Atkins JN, Fehrenbacher L, Bear HD, Baez-Diaz L, Sarwar S, Margolese RG, Farrar WB, Brufsky AM, Shibata HR, Bandos H, Paik S, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1183-92. Epub 2013 Oct 4. [https://doi.org/10.1016/S1470-2045(13)70411-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24095300/ PubMed] [https://clinicaltrials.gov/study/NCT00486668 NCT00486668] |
− | + | ==AC-THL (Paclitaxel) {{#subobject:gjaag1|Regimen=1}}== | |
− | ==AC - | + | AC-THL: '''<u>A</u>'''driamycin (Doxorubicin) and '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axol (Paclitaxel), '''<u>H</u>'''erceptin (Trastuzumab), '''<u>L</u>'''apatinib |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
− | AC - | ||
− | |||
===Regimen {{#subobject:ca2389|Variant=1}}=== | ===Regimen {{#subobject:ca2389|Variant=1}}=== | ||
− | {| | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | | | + | !style="width: 20%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Dates of enrollment |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |rowspan=2|[ | + | |rowspan=2|[https://doi.org/10.1016/S1470-2045(13)70411-X Robidoux et al. 2013 (NSABP B-41)] |
− | |rowspan=2 style="background-color:# | + | |rowspan=2|2007-2011 |
− | |AC - | + | |rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc) |
− | |style="background-color:# | + | |1. [[#AC-TH_.28Paclitaxel.29|AC-TH]] |
+ | |style="background-color:#d9ef8b"|Might have superior pCR rate (primary endpoint) | ||
|- | |- | ||
− | |AC - | + | |2. [[#AC-TL_.28Paclitaxel.29|AC-TL]] |
− | |style="background-color:# | + | |style="background-color:#d9ef8b"|Might have superior pCR rate (primary endpoint) |
|- | |- | ||
|} | |} | ||
− | ====Chemotherapy, AC portion==== | + | ''Note: This lapatinib dosing was based on a mid-protocol amendment due to excess diarrhea reported in other trials.'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, AC portion (cycles 1 to 4)==== | ||
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Chemotherapy, THL portion (cycles 5 to 8)==== | |
− | |||
− | |||
− | ====Chemotherapy, THL portion==== | ||
*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | ||
+ | ====Targeted therapy, THL portion (cycles 5 to 8)==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22 |
− | **Cycles | + | **Cycles 6 to 8: 2 mg/kg IV once per day on days 1, 8, 15, 22 |
− | *[[Lapatinib (Tykerb)]] 750 mg PO once per day | + | *[[Lapatinib (Tykerb)]] as follows: |
− | + | **Cycles 5 to 8: 750 mg PO once per day | |
− | '''28-day cycle for 4 cycles | + | '''21-day cycle for 4 cycles, then 28-day cycle for 4 cycles (AC x 4; THL x 4)''' |
− | + | </div> | |
− | + | <div class="toccolours" style="background-color:#cbd5e7"> | |
+ | ====Subsequent treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]], then adjuvant [[#Trastuzumab_monotherapy_2|trastuzumab]] for a total of 52 weeks of therapy | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Robidoux A, Tang G, Rastogi P, Geyer CE Jr, Azar CA, Atkins JN, Fehrenbacher L, Bear HD, Baez-Diaz L, Sarwar S, Margolese RG, Farrar WB, Brufsky AM, Shibata HR, Bandos H, Paik S, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1183-92. Epub 2013 Oct 4. [ | + | # '''NSABP B-41:''' Robidoux A, Tang G, Rastogi P, Geyer CE Jr, Azar CA, Atkins JN, Fehrenbacher L, Bear HD, Baez-Diaz L, Sarwar S, Margolese RG, Farrar WB, Brufsky AM, Shibata HR, Bandos H, Paik S, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1183-92. Epub 2013 Oct 4. [https://doi.org/10.1016/S1470-2045(13)70411-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24095300/ PubMed] [https://clinicaltrials.gov/study/NCT00486668 NCT00486668] |
− | + | ==AC-THP (Docetaxel) {{#subobject:74dc52|Regimen=1}}== | |
− | ==AC -> | + | AC-THP: '''<u>A</u>'''driamycin (Doxorubicin) and '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axotere (Docetaxel), '''<u>H</u>'''erceptin (Trastuzumab), '''<u>P</u>'''ertuzumab |
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen {{#subobject:jop01a|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/s1470-2045(20)30536-2 Tan et al. 2021 (FeDeriCa)] | ||
+ | |2018-06-14 to 2018-12-24 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#ddAC-THP_.28Paclitaxel.2C_Phesgo.29|ddAC-THP (Paclitaxel, Phesgo)]]<br>1b. [[#AC-THP_.28Docetaxel.2C_Phesgo.29|AC-THP (Docetaxel, Phesgo)]] | ||
+ | |style="background-color:#eeee01"|Non-inferior serum trough | ||
|- | |- | ||
− | |||
|} | |} | ||
− | AC -> | + | ''Note: Docetaxel dose was esclated in cycles 6 to 8 if tolerated.'' |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | ===Regimen {{#subobject: | + | ====Chemotherapy, AC portion (cycles 1 to 4)==== |
− | {| | + | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 |
− | | | + | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 |
− | |[[Levels_of_Evidence#Evidence| | + | ====Chemotherapy, THP portion (cycles 5 to 8)==== |
− | | | + | *[[Docetaxel (Taxotere)]] as follows: |
− | |[[Levels_of_Evidence# | + | **Cycle 5: 75 mg/m<sup>2</sup> IV once on day 1 |
+ | **Cycles 6 to 8: 100 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, THP portion (cycles 5 to 8)==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 5: 8 mg/kg IV once on day 1 | ||
+ | **Cycles 6 to 8: 6 mg/kg IV once on day 1 | ||
+ | *[[Pertuzumab (Perjeta)]] as follows: | ||
+ | **Cycle 5: 840 mg IV once on day 1 | ||
+ | **Cycles 6 to 8: 420 mg IV once on day 1 | ||
+ | '''21-day cycle for 8 cycles (AC x 4; THP x 4)''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]], then adjuvant [[#Pertuzumab_.26_Trastuzumab_.28HP.29_888|HP]] | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''FeDeriCa:''' Tan AR, Im SA, Mattar A, Colomer R, Stroyakovskii D, Nowecki Z, De Laurentiis M, Pierga JY, Jung KH, Schem C, Hogea A, Badovinac Crnjevic T, Heeson S, Shivhare M, Kirschbrown WP, Restuccia E, Jackisch C; FeDeriCa study group. Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection plus chemotherapy in HER2-positive early breast cancer (FeDeriCa): a randomised, open-label, multicentre, non-inferiority, phase 3 study. Lancet Oncol. 2021 Jan;22(1):85-97. Epub 2020 Dec 21. Erratum in: Lancet Oncol. 2021 Feb;22(2):e42. [https://doi.org/10.1016/s1470-2045(20)30536-2 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33357420/ PubMed] [https://clinicaltrials.gov/study/NCT03493854 NCT03493854] | ||
+ | ==AC-THP (Docetaxel, Phesgo) {{#subobject:bju3c2|Regimen=1}}== | ||
+ | AC-THP (Phesgo): '''<u>A</u>'''driamycin (Doxorubicin) and '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axotere (Docetaxel) and Phesgo | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:bjvi1a|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/s1470-2045(20)30536-2 Tan et al. 2021 (FeDeriCa)] | ||
+ | |2018-06-14 to 2018-12-24 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-RT-switch-ic) | ||
+ | |1a. [[#ddAC-THP_.28Paclitaxel.29|ddAC-THP]]<br>1b. [[#AC-THP_.28Docetaxel.29|AC-THP]] | ||
+ | |style="background-color:#eeee01"|Non-inferior serum trough (primary endpoint) | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: Docetaxel dose was esclated in cycles 6 to 8 if tolerated.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, AC portion (cycles 1 to 4)==== | ||
+ | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Chemotherapy, THP (Phesgo) portion (cycles 5 to 8)==== | ||
+ | *[[Docetaxel (Taxotere)]] as follows: | ||
+ | **Cycle 5: 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | **Cycles 6 to 8: 100 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, THP (Phesgo) portion (cycles 5 to 8)==== | ||
+ | *[[Pertuzumab and Trastuzumab hyaluronidase (Phesgo)]] as follows: | ||
+ | **Cycle 5: 1200/600 SC once on day 1 | ||
+ | **Cycles 6 to 8: 600/600 SC once on day 1 | ||
+ | '''21-day cycle for 8 cycles (AC x 4; THP (Phesgo) x 4)''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]], then adjuvant [[#Pertuzumab_and_Trastuzumab_hyaluronidase_monotherapy|Phesgo]] | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''FeDeriCa:''' Tan AR, Im SA, Mattar A, Colomer R, Stroyakovskii D, Nowecki Z, De Laurentiis M, Pierga JY, Jung KH, Schem C, Hogea A, Badovinac Crnjevic T, Heeson S, Shivhare M, Kirschbrown WP, Restuccia E, Jackisch C; FeDeriCa study group. Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection plus chemotherapy in HER2-positive early breast cancer (FeDeriCa): a randomised, open-label, multicentre, non-inferiority, phase 3 study. Lancet Oncol. 2021 Jan;22(1):85-97. Epub 2020 Dec 21. Erratum in: Lancet Oncol. 2021 Feb;22(2):e42. [https://doi.org/10.1016/s1470-2045(20)30536-2 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33357420/ PubMed] [https://clinicaltrials.gov/study/NCT03493854 NCT03493854] | ||
+ | ==ddAC-THP (Paclitaxel) {{#subobject:bgac16|Regimen=1}}== | ||
+ | ddAC-THP: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>A</u>'''driamycin (Doxorubicin) and '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axol (Paclitaxel), '''<u>H</u>'''erceptin (Trastuzumab), '''<u>P</u>'''ertuzumab | ||
+ | <br>ddAC-PacPH: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>A</u>'''driamycin (Doxorubicin) and '''<u>C</u>'''yclophosphamide, followed by '''<u>Pac</u>'''litaxel, '''<u>P</u>'''ertuzumab, '''<u>H</u>'''erceptin (Trastuzumab) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:bjvi1a|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5888999/ Swain et al. 2018 (BERENICE)] | ||
+ | |2014-2015 | ||
+ | | style="background-color:#91cf61" |Phase 2 (RT) | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | + | |[https://doi.org/10.1016/s1470-2045(20)30536-2 Tan et al. 2021 (FeDeriCa)] | |
− | | | + | |2018-06-14 to 2018-12-24 |
− | |AC - | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#ddAC-THP_.28Paclitaxel.2C_Phesgo.29|ddAC-THP (Paclitaxel, Phesgo)]]<br>1b. [[#AC-THP_.28Docetaxel.2C_Phesgo.29|AC-THP (Docetaxel, Phesgo)]] |
+ | |style="background-color:#eeee01"|Non-inferior serum trough | ||
|- | |- | ||
− | | | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9426828/ Huober et al. 2022 (IMpassion050)] |
− | |style="background-color:# | + | |2019-01 to 2020-08 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#ddAC-THP_.26_Atezolizumab_999|ddAC-THP & Atezolizumab]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of pCR rate | ||
|- | |- | ||
|} | |} | ||
− | ====Chemotherapy, | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | + | ====Chemotherapy, ddAC portion (cycles 1 to 4)==== |
+ | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Supportive therapy, ddAC portion (cycles 1 to 4)==== | |
− | + | *[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] support (drug/dose/schedule not specified) | |
− | + | ====Chemotherapy, THP portion (cycles 5 to 8)==== | |
− | ====Chemotherapy, | ||
*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | ||
− | *[[ | + | ====Targeted therapy, THP portion (cycles 5 to 8)==== |
− | + | *[[Trastuzumab (Herceptin)]] as follows: | |
− | ''' | + | **Cycle 5: 8 mg/kg IV once on day 1 |
− | + | **Cycles 6 to 8: 6 mg/kg IV once on day 1 | |
− | + | *[[Pertuzumab (Perjeta)]] as follows: | |
− | + | **Cycle 5: 840 mg IV once on day 1 | |
+ | **Cycles 6 to 8: 420 mg IV once on day 1 | ||
+ | '''14-day cycle for 4 cycles, then 21-day cycle for 4 cycles (ddAC x 4; THP x 4)''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]], then adjuvant [[#Pertuzumab_.26_Trastuzumab_.28HP.29_888|HP]] | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # | + | # '''BERENICE:''' Swain SM, Ewer MS, Viale G, Delaloge S, Ferrero JM, Verrill M, Colomer R, Vieira C, Werner TL, Douthwaite H, Bradley D, Waldron-Lynch M, Kiermaier A, Eng-Wong J, Dang C; BERENICE Study Group. Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): a phase II, open-label, multicenter, multinational cardiac safety study. Ann Oncol. 2018 Mar 1;29(3):646-653. [https://doi.org/10.1093/annonc/mdx773 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5888999/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/29253081/ PubMed] [https://clinicaltrials.gov/study/NCT02132949 NCT02132949] |
− | + | ##'''Update:''' Dang C, Ewer MS, Delaloge S, Ferrero JM, Colomer R, de la Cruz-Merino L, Werner TL, Dadswell K, Verrill M, Eiger D, Sarkar S, de Haas SL, Restuccia E, Swain SM. BERENICE Final Analysis: Cardiac Safety Study of Neoadjuvant Pertuzumab, Trastuzumab, and Chemotherapy Followed by Adjuvant Pertuzumab and Trastuzumab in HER2-Positive Early Breast Cancer. Cancers (Basel). 2022 May 24;14(11):2596. [https://doi.org/10.3390/cancers14112596 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9179451/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35681574/ PubMed] | |
− | == | + | # '''FeDeriCa:''' Tan AR, Im SA, Mattar A, Colomer R, Stroyakovskii D, Nowecki Z, De Laurentiis M, Pierga JY, Jung KH, Schem C, Hogea A, Badovinac Crnjevic T, Heeson S, Shivhare M, Kirschbrown WP, Restuccia E, Jackisch C; FeDeriCa study group. Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection plus chemotherapy in HER2-positive early breast cancer (FeDeriCa): a randomised, open-label, multicentre, non-inferiority, phase 3 study. Lancet Oncol. 2021 Jan;22(1):85-97. Epub 2020 Dec 21. Erratum in: Lancet Oncol. 2021 Feb;22(2):e42. [https://doi.org/10.1016/s1470-2045(20)30536-2 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33357420/ PubMed] [https://clinicaltrials.gov/study/NCT03493854 NCT03493854] |
− | {| class="wikitable" style=" | + | # '''IMpassion050:''' Huober J, Barrios CH, Niikura N, Jarząb M, Chang YC, Huggins-Puhalla SL, Pedrini J, Zhukova L, Graupner V, Eiger D, Henschel V, Gochitashvili N, Lambertini C, Restuccia E, Zhang H; IMpassion050 Trial Investigators. Atezolizumab With Neoadjuvant Anti-Human Epidermal Growth Factor Receptor 2 Therapy and Chemotherapy in Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: Primary Results of the Randomized Phase III IMpassion050 Trial. J Clin Oncol. 2022 Sep 1;40(25):2946-2956. Epub 2022 Jun 28. [https://doi.org/10.1200/jco.21.02772 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9426828/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35763704/ PubMed] [https://clinicaltrials.gov/study/NCT03726879 NCT03726879] |
+ | ==ddAC-THP (Paclitaxel, Phesgo) {{#subobject:bgau52|Regimen=1}}== | ||
+ | ddAC-THP (Phesgo): '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>A</u>'''driamycin (Doxorubicin) and '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axol (Paclitaxel) and Phesgo | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:bjvi1a|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/s1470-2045(20)30536-2 Tan et al. 2021 (FeDeriCa)] | ||
+ | |2018-06-14 to 2018-12-24 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-RT-switch-ic) | ||
+ | |1a. [[#ddAC-THP_.28Paclitaxel.29|ddAC-THP]]<br>1b. [[#AC-THP_.28Docetaxel.29|AC-THP]] | ||
+ | |style="background-color:#eeee01"|Non-inferior serum trough (primary endpoint) | ||
|- | |- | ||
− | |||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, ddAC portion (cycles 1 to 4)==== | ||
+ | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Supportive therapy, ddAC portion (cycles 1 to 4)==== | ||
+ | *[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] support (drug/dose/schedule not specified) | ||
+ | ====Chemotherapy, THP (Phesgo) portion (cycles 5 to 8)==== | ||
+ | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | ||
+ | ====Targeted therapy, THP (Phesgo) portion (cycles 5 to 8)==== | ||
+ | *[[Pertuzumab and Trastuzumab hyaluronidase (Phesgo)]] as follows: | ||
+ | **Cycle 5: 1200/600 SC once on day 1 | ||
+ | **Cycles 6 to 8: 600/600 SC once on day 1 | ||
+ | '''14-day cycle for 4 cycles, then 21-day cycle for 4 cycles (ddAC x 4; THP (Phesgo) x 4)''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]], then adjuvant [[#Pertuzumab_and_Trastuzumab_hyaluronidase_monotherapy|Phesgo]] | ||
+ | </div></div> | ||
− | + | ===References=== | |
+ | # '''FeDeriCa:''' Tan AR, Im SA, Mattar A, Colomer R, Stroyakovskii D, Nowecki Z, De Laurentiis M, Pierga JY, Jung KH, Schem C, Hogea A, Badovinac Crnjevic T, Heeson S, Shivhare M, Kirschbrown WP, Restuccia E, Jackisch C; FeDeriCa study group. Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection plus chemotherapy in HER2-positive early breast cancer (FeDeriCa): a randomised, open-label, multicentre, non-inferiority, phase 3 study. Lancet Oncol. 2021 Jan;22(1):85-97. Epub 2020 Dec 21. Erratum in: Lancet Oncol. 2021 Feb;22(2):e42. [https://doi.org/10.1016/s1470-2045(20)30536-2 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33357420/ PubMed] [https://clinicaltrials.gov/study/NCT03493854 NCT03493854] | ||
− | ===Regimen {{#subobject: | + | ==AC-TL (Paclitaxel) {{#subobject:gcjb91|Regimen=1}}== |
− | {| | + | AC-TL: '''<u>A</u>'''driamycin (Doxorubicin) and '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axol (Paclitaxel) & '''<u>L</u>'''apatinib |
− | | | + | </div></div><br> |
− | |[[Levels_of_Evidence#Evidence| | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | | | + | ===Regimen {{#subobject:6dda48|Variant=1}}=== |
− | |[[Levels_of_Evidence# | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |rowspan=2|[ | + | |rowspan=2|[https://doi.org/10.1016/S1470-2045(13)70411-X Robidoux et al. 2013 (NSABP B-41)] |
− | |rowspan=2 style="background-color:# | + | |rowspan=2|2007-2011 |
− | | | + | |rowspan=2 style="background-color:#1a9851"|Phase 3 (E-switch-ic) |
− | |style="background-color:# | + | |1. [[#AC-TH_.28Paclitaxel.29|AC-TH]] |
+ | |style="background-color:#ffffbf"|Did not meet primary endpoint of pCR rate | ||
|- | |- | ||
− | | | + | |2. [[#AC-THL_.28Paclitaxel.29|AC-THL]] |
− | |style="background-color:# | + | |style="background-color:#fee08b"|Might have inferior pCR rate (primary endpoint) |
|- | |- | ||
|} | |} | ||
− | ==== | + | ''Note: This lapatinib dosing was based on a mid-protocol amendment due to excess diarrhea reported in other trials.'' |
− | *[[ | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | + | ====Chemotherapy, AC portion (cycles 1 to 4)==== | |
− | + | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | |
− | *[[ | + | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 |
− | + | ====Chemotherapy, TL portion (cycles 5 to 8)==== | |
− | + | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | |
− | *[[ | + | ====Targeted therapy, TL portion (cycles 5 to 8)==== |
− | + | *[[Lapatinib (Tykerb)]] 1250 mg PO once per day on days 1 to 28 | |
− | + | '''21-day cycle for 4 cycles, then 28-day cycle for 4 cycles (AC x 4; TL x 4)''' | |
− | + | </div> | |
− | + | <div class="toccolours" style="background-color:#cbd5e7"> | |
− | |||
− | ==== | ||
− | *[[ | ||
− | |||
− | |||
− | '''21-day cycles, | ||
+ | ====Subsequent treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]], then adjuvant [[#Trastuzumab_monotherapy_2|trastuzumab]] for a total of 52 weeks of therapy | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # | + | # '''NSABP B-41:''' Robidoux A, Tang G, Rastogi P, Geyer CE Jr, Azar CA, Atkins JN, Fehrenbacher L, Bear HD, Baez-Diaz L, Sarwar S, Margolese RG, Farrar WB, Brufsky AM, Shibata HR, Bandos H, Paik S, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1183-92. Epub 2013 Oct 4. [https://doi.org/10.1016/S1470-2045(13)70411-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24095300/ PubMed] [https://clinicaltrials.gov/study/NCT00486668 NCT00486668] |
− | ==TH ( | + | ==EC-TH (Docetaxel) {{#subobject:7jb8ad|Regimen=1}}== |
− | {| class="wikitable" style=" | + | EC-TH: '''<u>E</u>'''pirubicin & '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axotere (Docetaxel) & '''<u>H</u>'''erceptin (Trastuzumab) |
+ | <br>EC-DT: '''<u>E</u>'''pirubicin & '''<u>C</u>'''yclophosphamide, followed by '''<u>D</u>'''ocetaxel & '''<u>T</u>'''rastuzumab | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:a889a0|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3950860/ Alba et al. 2014 (GEICAM 2006-14)] | ||
+ | |2009-02 to 2010-10 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[Stub#EC-TL_.28Docetaxel.29|EC-TL]] | ||
+ | | style="background-color:#1a9850" |Superior pCR rate (primary endpoint) | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
+ | ====Chemotherapy, EC portion (cycles 1 to 4)==== | ||
+ | *[[Epirubicin (Ellence)]] 90 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Chemotherapy, TH portion (cycles 5 to 8)==== | ||
+ | *[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, TH portion (cycles 5 to 8)==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 5: 8 mg/kg IV once on day 1 | ||
+ | **Cycles 6 to 8: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycle for 8 cycles (EC x 4; TH x 4)''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''GEICAM 2006-14:''' Alba E, Albanell J, de la Haba J, Barnadas A, Calvo L, Sánchez-Rovira P, Ramos M, Rojo F, Burgués O, Carrasco E, Caballero R, Porras I, Tibau A, Cámara MC, Lluch A. Trastuzumab or lapatinib with standard chemotherapy for HER2-positive breast cancer: results from the GEICAM/2006-14 trial. Br J Cancer. 2014 Mar 4;110(5):1139-47. Epub 2014 Jan 23. [https://doi.org/10.1038/bjc.2013.831 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3950860/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24457911/ PubMed] [https://clinicaltrials.gov/study/NCT00841828 NCT00841828] | ||
− | ===Regimen {{#subobject: | + | ==ECH-TH (Docetaxel) {{#subobject:6828f5|Regimen=1}}== |
− | {| | + | ECH-TH: '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''erceptin (Trastuzumab), followed by '''<u>T</u>'''axotere (Docetaxel) & '''<u>H</u>'''erceptin (Trastuzumab) |
− | | | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | |[[Levels_of_Evidence#Evidence| | + | ===Regimen {{#subobject:436755|Variant=1}}=== |
− | | | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|Study |
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(11)70397-7 Untch et al. 2012 (GeparQuinto<sub>HER2</sub>)] |
− | |style="background-color:# | + | |2007-2010 |
− | | | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |[[#ECL-TL_.28Docetaxel.29_999|ECL-TL]] |
+ | | style="background-color:#91cf60" |Seems to have superior pCR rate (primary endpoint) | ||
|- | |- | ||
|} | |} | ||
− | ====Chemotherapy, | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[ | + | ====Chemotherapy, ECH portion (cycles 1 to 4)==== |
+ | *[[Epirubicin (Ellence)]] 90 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, ECH portion (cycles 1 to 4)==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | ** | + | **Cycle 1: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 2 to 4: 6 mg/kg IV once on day 1 |
− | + | ====Chemotherapy, TH portion (cycles 5 to 8)==== | |
− | + | *[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1 | |
− | + | ====Targeted therapy, TH portion (cycles 5 to 8)==== | |
− | ====Chemotherapy, | + | *[[Trastuzumab (Herceptin)]] 6 mg/kg IV once on day 1 |
− | *[[ | + | '''21-day cycle for 8 cycles (ECH x 4; TH x 4)''' |
− | *[[ | + | </div> |
− | + | <div class="toccolours" style="background-color:#cbd5e7"> | |
− | ''' | + | ====Subsequent treatment==== |
− | + | *[[Surgery#Breast_cancer_surgery|Surgery]], then adjuvant [[#Trastuzumab_monotherapy_2|trastuzumab]] for 1 year total | |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | < | + | # '''GeparQuinto<sub>HER2</sub>:''' Untch M, Loibl S, Bischoff J, Eidtmann H, Kaufmann M, Blohmer JU, Hilfrich J, Strumberg D, Fasching PA, Kreienberg R, Tesch H, Hanusch C, Gerber B, Rezai M, Jackisch C, Huober J, Kühn T, Nekljudova V, von Minckwitz G; German Breast Group; Arbeitsgemeinschaft Gynäkologische Onkologie-Breast Study Group. Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial. Lancet Oncol. 2012 Feb;13(2):135-44. Epub 2012 Jan 17. [https://doi.org/10.1016/S1470-2045(11)70397-7 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22257523/ PubMed] [https://clinicaltrials.gov/study/NCT00567554 NCT00567554] |
− | + | ## '''Update:''' Untch M, von Minckwitz G, Gerber B, Schem C, Rezai M, Fasching PA, Tesch H, Eggemann H, Hanusch C, Huober J, Solbach C, Jackisch C, Kunz G, Blohmer JU, Hauschild M, Fehm T, Nekljudova V, Loibl S; GBG; AGO-B Study Group. Survival analysis after neoadjuvant chemotherapy with trastuzumab or lapatinib in patients with human epidermal growth factor receptor 2-positive breast cancer in the GeparQuinto (G5) study (GBG 44). J Clin Oncol. 2018 May 1;36(13):1308-1316. Epub 2018 Mar 15. [https://doi.org/10.1200/JCO.2017.75.9175 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29543566/ PubMed] | |
− | ==TH ( | + | ==FEC-TH (Paclitaxel) {{#subobject:ed84df|Regimen=1}}== |
− | {| class="wikitable" style=" | + | FEC-TH: '''<u>F</u>'''luorouracil, '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axol (Paclitaxel) & '''<u>H</u>'''erceptin (Trastuzumab) |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:9e61ad|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176878/ Buzdar et al. 2013 (ACOSOG Z1041)] |
− | + | |2007-2011 | |
− | + | | style="background-color:#1a9851" |Phase 3 (C) | |
− | + | |[[#TH-FEC_.26_H_.28Paclitaxel.29_999|TH-FEC & H]] | |
− | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of pCR | |
− | |||
− | | | ||
− | |[[ | ||
− | |||
− | |||
− | |||
− | |||
− | | | ||
− | |||
− | |style="background-color:# | ||
|- | |- | ||
|} | |} | ||
− | == | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | + | ====Chemotherapy, FEC portion (cycles 1 to 4)==== | |
− | + | *[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once on day 1 | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | ====Chemotherapy, FEC | ||
− | *[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once | ||
*[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1 | *[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1 | ||
− | *[[Trastuzumab (Herceptin)]] 2 mg/kg IV once per day on days 1, 8, 15 | + | ====Chemotherapy, TH portion (cycles 5 to 8)==== |
− | + | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | |
− | '''21-day cycle for 4 | + | ====Targeted therapy, TH portion==== |
− | + | *[[Trastuzumab (Herceptin)]] as follows: | |
+ | **Cycle 5: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15 | ||
+ | **Cycles 6 to 8: 2 mg/kg IV once per day on days 1, 8, 15 | ||
+ | '''21-day cycle for 8 cycles (FEC x 4; TH x 4)'' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|surgery]] | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Buzdar AU, | + | # '''ACOSOG Z1041:''' Buzdar AU, Suman VJ, Meric-Bernstam F, Leitch AM, Ellis MJ, Boughey JC, Unzeitig G, Royce M, McCall LM, Ewer MS, Hunt KK; American College of Surgeons Oncology Group. Fluorouracil, epirubicin, and cyclophosphamide (FEC-75) followed by paclitaxel plus trastuzumab versus paclitaxel plus trastuzumab followed by FEC-75 plus trastuzumab as neoadjuvant treatment for patients with HER2-positive breast cancer (Z1041): a randomised, controlled, phase 3 trial. Lancet Oncol. 2013 Dec;14(13):1317-25. Epub 2013 Nov 13. [https://doi.org/10.1016/S1470-2045(13)70502-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176878/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24239210/ PubMed] [https://clinicaltrials.gov/study/NCT00513292 NCT00513292] |
− | ## '''Update:''' Buzdar AU, | + | ## '''Update:''' Buzdar AU, Suman VJ, Meric-Bernstam F, Leitch AM, Ellis MJ, Boughey JC, Unzeitig GW, Royce ME, Hunt KK. Disease-Free and Overall Survival Among Patients With Operable HER2-Positive Breast Cancer Treated With Sequential vs Concurrent Chemotherapy: The ACOSOG Z1041 (Alliance) Randomized Clinical Trial. JAMA Oncol. 2019 Jan 1;5(1):45-50. [https://doi.org/10.1001/jamaoncol.2018.3691 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331049/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30193295/ PubMed] |
− | + | ==FEC-THP (Docetaxel) {{#subobject:egjc1f|Regimen=1}}== | |
− | == | + | FEC-THP: '''<u>F</u>'''luorouracil, '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axotere (Docetaxel), '''<u>H</u>'''erceptin (Trastuzumab), '''<u>P</u>'''ertuzumab |
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #1, 3 x 3 {{#subobject:7ddba5|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 17%"|Study | ||
+ | !style="width: 15%"|Dates of enrollment | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 17%"|Comparator | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1093/annonc/mdt182 Schneeweiss et al. 2013 (TRYPHAENA)] | ||
+ | |2009-2011 | ||
+ | |style="background-color:#1a9851"|Randomized Phase 2 (E-RT-switch-ic) | ||
+ | |1. [[#FEC_.26_HP-THP_.28Docetaxel.29_888|FEC & HP-THP]]<br>2. [[#TCHP_.28Docetaxel.29|TCHP]] | ||
+ | |style="background-color:#d3d3d3"|Not reported | ||
+ | | style="background-color:#ffffbf" |Similar rates of LVSD (co-primary endpoint) | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | + | ====Chemotherapy, FEC portion (cycles 1 to 3)==== | |
− | ===Regimen # | + | *[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once on day 1 |
− | {| | + | *[[Epirubicin (Ellence)]] 100 mg/m<sup>2</sup> IV once on day 1 |
− | | | + | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 |
− | |[[Levels_of_Evidence#Evidence| | + | ====Chemotherapy, THP portion (cycles 4 to 6)==== |
− | + | *[[Docetaxel (Taxotere)]] as follows: | |
− | + | **Cycle 4: 75 mg/m<sup>2</sup> IV once on day 1 | |
+ | **Cycles 5 & 6; if no toxic effects occurred: 100 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, THP portion (cycles 4 to 6)==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 4: 8 mg/kg IV once on day 1 | ||
+ | **Cycles 5 & 6: 6 mg/kg IV once on day 1 | ||
+ | *[[Pertuzumab (Perjeta)]] as follows: | ||
+ | **Cycle 4: 840 mg IV once on day 1 | ||
+ | **Cycles 5 & 6: 420 mg IV once on day 1 | ||
+ | '''21-day cycle for 6 cycles (FEC x 3; THP x 3)''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]], then further adjuvant treatment (radiotherapy, chemotherapy, hormonal treatment) according to local guidelines (a total of 1 year of trastuzumab was given) | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, 4 x 4 {{#subobject:65gba5|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5888999/ Swain et al. 2018 (BERENICE)] |
− | | | + | |2014-2015 |
− | + | | style="background-color:#91cf61" |Phase 2 (RT) | |
− | |style="background-color:# | ||
|- | |- | ||
|} | |} | ||
− | ====Chemotherapy, | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[ | + | ====Chemotherapy, FEC portion (cycles 1 to 4)==== |
+ | *[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Epirubicin (Ellence)]] 100 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Chemotherapy, THP portion (cycles 5 to 8)==== | ||
+ | *[[Docetaxel (Taxotere)]] as follows: | ||
+ | **Cycle 5: 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | **Cycles 6 to 8; if no toxic effects occurred: 100 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, THP portion (cycles 5 to 8)==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 8 mg/kg IV once on day 1 |
− | **Cycles | + | **Cycles 6 to 8: 6 mg/kg IV once on day 1 |
− | + | *[[Pertuzumab (Perjeta)]] as follows: | |
− | '''21-day cycle for 4 | + | **Cycle 5: 840 mg IV once on day 1 |
− | + | **Cycles 6 to 8: 420 mg IV once on day 1 | |
− | ==== | + | '''21-day cycle for 8 cycles (FEC x 4; THP x 4)''' |
− | *[[ | + | </div> |
− | + | <div class="toccolours" style="background-color:#cbd5e7"> | |
− | + | ====Subsequent treatment==== | |
− | + | *[[Surgery#Breast_cancer_surgery|Surgery]], then adjuvant [[#Pertuzumab_.26_Trastuzumab_.28HP.29_888|HP]] | |
− | + | </div></div> | |
− | ''' | + | ===References=== |
− | + | # '''TRYPHAENA:''' Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, Tausch C, Seo JH, Tsai YF, Ratnayake J, McNally V, Ross G, Cortés J. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013 Sep;24(9):2278-84. Epub 2013 May 22. [https://doi.org/10.1093/annonc/mdt182 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23704196/ PubMed] [https://clinicaltrials.gov/study/NCT00976989 NCT00976989] | |
− | ===Regimen | + | ##'''Update:''' Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Waldron-Lynch M, Eng-Wong J, Kirk S, Cortés J. Long-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: Evaluating pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer. Eur J Cancer. 2018 Jan;89:27-35. Epub 2017 Dec 8. [https://doi.org/10.1016/j.ejca.2017.10.021 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29223479/ PubMed] |
− | {| | + | # '''BERENICE:''' Swain SM, Ewer MS, Viale G, Delaloge S, Ferrero JM, Verrill M, Colomer R, Vieira C, Werner TL, Douthwaite H, Bradley D, Waldron-Lynch M, Kiermaier A, Eng-Wong J, Dang C; BERENICE Study Group. Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): a phase II, open-label, multicenter, multinational cardiac safety study. Ann Oncol. 2018 Mar 1;29(3):646-653. [https://doi.org/10.1093/annonc/mdx773 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5888999/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/29253081/ PubMed] [https://clinicaltrials.gov/study/NCT02132949 NCT02132949] |
− | | | + | ##'''Update:''' Dang C, Ewer MS, Delaloge S, Ferrero JM, Colomer R, de la Cruz-Merino L, Werner TL, Dadswell K, Verrill M, Eiger D, Sarkar S, de Haas SL, Restuccia E, Swain SM. BERENICE Final Analysis: Cardiac Safety Study of Neoadjuvant Pertuzumab, Trastuzumab, and Chemotherapy Followed by Adjuvant Pertuzumab and Trastuzumab in HER2-Positive Early Breast Cancer. Cancers (Basel). 2022 May 24;14(11):2596. [https://doi.org/10.3390/cancers14112596 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9179451/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35681574/ PubMed] |
− | |[[Levels_of_Evidence#Evidence| | + | ==Neratinib & Paclitaxel, then AC {{#subobject:bd4482|Regimen=1}}== |
− | | | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | |[[Levels_of_Evidence# | + | ===Regimen {{#subobject:3751fa|Variant=1}}=== |
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259558/ Park et al. 2016 (I-SPY 2 neratinib)] |
− | |style="background-color:# | + | |2010-2013 |
− | |TH -> | + | |style="background-color:#1a9851"|Adaptively Randomized Phase 2 (E-switch-ic) |
− | |style="background-color:# | + | |1a. [[#TH-AC_.28Paclitaxel.29|TH-AC]]<br>1b. [[#TH-ddAC_.28Paclitaxel.29|TH-ddAC]] |
+ | |style="background-color:#91cf60"|Seems to have superior pCR rate (primary endpoint) | ||
|- | |- | ||
|} | |} | ||
− | ====Chemotherapy, | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[Paclitaxel (Taxol)]] | + | ====Targeted therapy, neratinib & paclitaxel portion (cycles 1 to 4)==== |
− | *[[ | + | *[[Neratinib (Nerlynx)]] 240 mg PO once per day |
− | + | ====Chemotherapy, neratinib & paclitaxel portion (cycles 1 to 4)==== | |
− | + | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | |
− | + | ====Supportive therapy, neratinib & paclitaxel portion (cycles 1 to 4)==== | |
− | ====Chemotherapy, | + | *[[Loperamide (Imodium)]] 4 mg PO once on day 1, then 2 mg PO once 8 hours later, then 2 mg PO twice per day for two weeks, then decreased per patient choice, started on day 1 of neratinib |
− | *[[ | + | ====Chemotherapy, AC portion (cycles 5 to 8)==== |
− | + | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | |
− | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 |
− | + | '''21-day cycle for 8 cycles (neratinib & paclitaxel x 4; AC x 4)''' | |
− | + | </div> | |
− | '''21-day cycle for 4 | + | <div class="toccolours" style="background-color:#cbd5e7"> |
− | + | ====Subsequent treatment==== | |
+ | *[[Surgery#Breast_cancer_surgery|surgery]] | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # | + | <!-- Presented in part by Dr. Park at the 104th annual meeting of the American Association for Cancer Research, Washington, DC, April 6–10, 2013. --> |
− | + | # '''I-SPY 2 neratinib:''' Park JW, Liu MC, Yee D, Yau C, van 't Veer LJ, Symmans WF, Paoloni M, Perlmutter J, Hylton NM, Hogarth M, DeMichele A, Buxton MB, Chien AJ, Wallace AM, Boughey JC, Haddad TC, Chui SY, Kemmer KA, Kaplan HG, Isaacs C, Nanda R, Tripathy D, Albain KS, Edmiston KK, Elias AD, Northfelt DW, Pusztai L, Moulder SL, Lang JE, Viscusi RK, Euhus DM, Haley BB, Khan QJ, Wood WC, Melisko M, Schwab R, Helsten T, Lyandres J, Davis SE, Hirst GL, Sanil A, Esserman LJ, Berry DA; I-SPY 2 Investigators. Adaptive randomization of neratinib in early breast cancer. N Engl J Med. 2016 Jul 7;375(1):11-22. [https://doi.org/10.1056/NEJMoa1513750 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259558/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27406346/ PubMed] [https://clinicaltrials.gov/study/NCT01042379 NCT01042379] | |
− | == | + | ==Neratinib & Paclitaxel, then ddAC {{#subobject:bdgcca|Regimen=1}}== |
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen {{#subobject:1dgcxa|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259558/ Park et al. 2016 (I-SPY 2 neratinib)] | ||
+ | |2010-2013 | ||
+ | |style="background-color:#1a9851"|Adaptively Randomized Phase 2 (E-switch-ic) | ||
+ | |1a. [[#TH-AC_.28Paclitaxel.29|TH-AC]]<br>1b. [[#TH-ddAC_.28Paclitaxel.29|TH-ddAC]] | ||
+ | |style="background-color:#91cf60"|Seems to have superior pCR rate (primary endpoint) | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | ===Regimen {{#subobject: | + | ====Targeted therapy, neratinib & paclitaxel portion (cycles 1 to 4)==== |
− | {| | + | *[[Neratinib (Nerlynx)]] 240 mg PO once per day |
− | | | + | ====Chemotherapy, neratinib & paclitaxel portion (cycles 1 to 4)==== |
− | |[[Levels_of_Evidence#Evidence| | + | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 |
− | | | + | ====Supportive therapy, neratinib & paclitaxel portion (cycles 1 to 4)==== |
− | |[[Levels_of_Evidence# | + | *[[Loperamide (Imodium)]] 4 mg PO once on day 1, then 2 mg PO once 8 hours later, then 2 mg PO twice per day for two weeks, then decreased per patient choice, started on day 1 of neratinib |
+ | ====Chemotherapy, ddAC portion (cycles 5 to 8)==== | ||
+ | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Supportive therapy, ddAC portion (cycles 5 to 8)==== | ||
+ | *[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2, given 24 hours after chemotherapy | ||
+ | '''21-day cycle for 4 cycles, then 14-day cycle for 4 cycles (neratinib & paclitaxel x 4; ddAC x 4)''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|surgery]] | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | <!-- Presented in part by Dr. Park at the 104th annual meeting of the American Association for Cancer Research, Washington, DC, April 6–10, 2013. --> | ||
+ | # '''I-SPY 2 neratinib:''' Park JW, Liu MC, Yee D, Yau C, van 't Veer LJ, Symmans WF, Paoloni M, Perlmutter J, Hylton NM, Hogarth M, DeMichele A, Buxton MB, Chien AJ, Wallace AM, Boughey JC, Haddad TC, Chui SY, Kemmer KA, Kaplan HG, Isaacs C, Nanda R, Tripathy D, Albain KS, Edmiston KK, Elias AD, Northfelt DW, Pusztai L, Moulder SL, Lang JE, Viscusi RK, Euhus DM, Haley BB, Khan QJ, Wood WC, Melisko M, Schwab R, Helsten T, Lyandres J, Davis SE, Hirst GL, Sanil A, Esserman LJ, Berry DA; I-SPY 2 Investigators. Adaptive randomization of neratinib in early breast cancer. N Engl J Med. 2016 Jul 7;375(1):11-22. [https://doi.org/10.1056/NEJMoa1513750 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259558/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27406346/ PubMed] [https://clinicaltrials.gov/study/NCT01042379 NCT01042379] | ||
+ | ==TH-AC (Paclitaxel) {{#subobject:647f67|Regimen=1}}== | ||
+ | TH-AC: '''<u>T</u>'''axol (Paclitaxel) & '''<u>H</u>'''erceptin (Trastuzumab), followed by '''<u>A</u>'''driamycin (Doxorubicin) & '''<u>C</u>'''yclophosphamide | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:b18877|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259558/ Park et al. 2016 (I-SPY 2 neratinib)] | |
− | | | + | |2010-2013 |
− | | | + | |style="background-color:#1a9851"|Adaptively Randomized Phase 2 (C) |
− | + | |1a. [[#Neratinib_.26_Paclitaxel.2C_then_AC|Neratinib & Paclitaxel, then AC]]<br>1b. [[#Neratinib_.26_Paclitaxel.2C_then_ddAC|Neratinib & Paclitaxel, then ddAC]] | |
− | + | |style="background-color:#fc8d59"|Seems to have inferior pCR rate | |
− | | | ||
− | |||
− | |||
− | |||
− | |style="background-color:# | ||
|- | |- | ||
|} | |} | ||
− | ====Chemotherapy==== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[ | + | ====Chemotherapy, TH portion (cycles 1 to 4)==== |
− | + | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | |
− | + | ====Targeted therapy, TH portion==== | |
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle 1: | + | **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15 |
− | **Cycles 2 to 4: | + | **Cycles 2 to 4: 2 mg/kg IV once per day on days 1, 8, 15 |
− | *[[ | + | ====Chemotherapy, AC portion (cycles 5 to 8)==== |
− | * | + | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 |
− | + | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | |
− | '''21-day cycle for 4 | + | '''21-day cycle for 8 cycles (TH x 4; AC x 4)''' |
− | + | </div> | |
− | + | <div class="toccolours" style="background-color:#cbd5e7"> | |
− | + | ====Subsequent treatment==== | |
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | + | <!-- Presented in part by Dr. Park at the 104th annual meeting of the American Association for Cancer Research, Washington, DC, April 6–10, 2013. --> | |
− | + | # '''I-SPY 2 neratinib:''' Park JW, Liu MC, Yee D, Yau C, van 't Veer LJ, Symmans WF, Paoloni M, Perlmutter J, Hylton NM, Hogarth M, DeMichele A, Buxton MB, Chien AJ, Wallace AM, Boughey JC, Haddad TC, Chui SY, Kemmer KA, Kaplan HG, Isaacs C, Nanda R, Tripathy D, Albain KS, Edmiston KK, Elias AD, Northfelt DW, Pusztai L, Moulder SL, Lang JE, Viscusi RK, Euhus DM, Haley BB, Khan QJ, Wood WC, Melisko M, Schwab R, Helsten T, Lyandres J, Davis SE, Hirst GL, Sanil A, Esserman LJ, Berry DA; I-SPY 2 Investigators. Adaptive randomization of neratinib in early breast cancer. N Engl J Med. 2016 Jul 7;375(1):11-22. [https://doi.org/10.1056/NEJMoa1513750 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259558/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27406346/ PubMed] [https://clinicaltrials.gov/study/NCT01042379 NCT01042379] | |
− | = | + | ==TH-ddAC (Paclitaxel) {{#subobject:6gcc67|Regimen=1}}== |
− | == | + | TH-ddAC: '''<u>T</u>'''axol (Paclitaxel) & '''<u>H</u>'''erceptin (Trastuzumab), followed by '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>A</u>'''driamycin (Doxorubicin) & '''<u>C</u>'''yclophosphamide |
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen {{#subobject:b18877|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259558/ Park et al. 2016 (I-SPY 2 neratinib)] |
− | + | |2010-2013 | |
− | + | |style="background-color:#1a9851"|Adaptively Randomized Phase 2 (C) | |
− | + | |1a. [[#Neratinib_.26_Paclitaxel.2C_then_AC|Neratinib & Paclitaxel, then AC]]<br>1b. [[#Neratinib_.26_Paclitaxel.2C_then_ddAC|Neratinib & Paclitaxel, then ddAC]] | |
− | + | |style="background-color:#fc8d59"|Seems to have inferior pCR rate | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | | | ||
− | |[[ | ||
− | |||
− | |||
− | |||
− | |style="background-color:# | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | + | ====Chemotherapy, TH portion (cycles 1 to 4)==== | |
− | ====Chemotherapy, | + | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 |
+ | ====Targeted therapy, TH portion==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15 | ||
+ | **Cycles 2 to 4: 2 mg/kg IV once per day on days 1, 8, 15 | ||
+ | ====Chemotherapy, ddAC portion (cycles 5 to 8)==== | ||
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Supportive therapy, ddAC portion (cycles 5 to 8)==== | |
− | + | *[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2, given 24 hours after chemotherapy | |
− | + | '''21-day cycle for 4 cycles, then 14-day cycle for 4 cycles (TH x 4; ddAC x 4)''' | |
− | ==== | + | </div> |
− | *[[ | + | <div class="toccolours" style="background-color:#cbd5e7"> |
− | + | ====Subsequent treatment==== | |
− | ''' | + | *[[Surgery#Breast_cancer_surgery|Surgery]] |
− | + | </div></div> | |
− | ==== | ||
− | *[[ | ||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
===References=== | ===References=== | ||
− | <!-- | + | <!-- Presented in part by Dr. Park at the 104th annual meeting of the American Association for Cancer Research, Washington, DC, April 6–10, 2013. --> |
− | # | + | # '''I-SPY 2 neratinib:''' Park JW, Liu MC, Yee D, Yau C, van 't Veer LJ, Symmans WF, Paoloni M, Perlmutter J, Hylton NM, Hogarth M, DeMichele A, Buxton MB, Chien AJ, Wallace AM, Boughey JC, Haddad TC, Chui SY, Kemmer KA, Kaplan HG, Isaacs C, Nanda R, Tripathy D, Albain KS, Edmiston KK, Elias AD, Northfelt DW, Pusztai L, Moulder SL, Lang JE, Viscusi RK, Euhus DM, Haley BB, Khan QJ, Wood WC, Melisko M, Schwab R, Helsten T, Lyandres J, Davis SE, Hirst GL, Sanil A, Esserman LJ, Berry DA; I-SPY 2 Investigators. Adaptive randomization of neratinib in early breast cancer. N Engl J Med. 2016 Jul 7;375(1):11-22. [https://doi.org/10.1056/NEJMoa1513750 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259558/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27406346/ PubMed] [https://clinicaltrials.gov/study/NCT01042379 NCT01042379] |
− | + | ==TH-FEC & H (Docetaxel) {{#subobject:d2476f|Regimen=1}}== | |
− | + | TH-FEC & H: '''<u>T</u>'''axotere (Docetaxel) & '''<u>H</u>'''erceptin (Trastuzumab), followed by '''<u>F</u>'''luorouracil, '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''erceptin (Trastuzumab) | |
− | == | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style=" | + | ===Regimen {{#subobject:7391c0|Variant=1}}=== |
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S1470-2045(12)70329-7 Ismael et al. 2012 (HannaH)] | ||
+ | |2009-10-19 to 2010-12-01 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#TH-FEC_.26_H_.28Docetaxel.2C_SC_Trastuzumab.29|TH-FEC & H (SC)]] | ||
+ | |style="background-color:#eeee01"|Non-inferior pCR rate | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/JCO.2017.74.0126 Pivot et al. 2018 (SB3-G31-BC)] |
− | + | |2014-04 to 2015-08 | |
− | + | |style="background-color:#1a9851"|Phase 3 (C) | |
− | + | |[[#TH-FEC_.26_H_.28Docetaxel.29_.28trastuzumab-dttb.29|TH-FEC & H (trastuzumab-dttb)]] | |
− | + | |style="background-color:#eeee01"|Equivalent bpCR rate (primary endpoint)<br>bpCR rate: 42% vs 51.7% | |
− | |||
− | |||
− | |||
− | | | ||
− | |[[ | ||
− | | | ||
− | |||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/s1470-2045(17)30434-5 Stebbing et al. 2017 (CT-P6 3.2)] |
− | |style="background-color:# | + | |2014-08-07 to 2016-05-06 |
− | + | |style="background-color:#1a9851"|Phase 3 (C) | |
− | |style="background-color:# | + | |[[#TH-FEC_.26_H_.28Docetaxel.29_.28trastuzumab-pkrb.29|TH-FEC & H (trastuzumab-pkrb)]] |
+ | |style="background-color:#eeee01"|Equivalent pCR rate (primary endpoint)<br>pCR rate: 50.4% vs 46.8% | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | ====Chemotherapy, | + | ====Chemotherapy, T portion (cycles 1 to 4)==== |
− | *[[ | + | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 |
− | *[[ | + | ====Chemotherapy, FEC portion (cycles 5 to 8)==== |
− | + | *[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once on day 1 | |
− | + | *[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1 | |
− | + | *[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1 | |
− | + | ====Targeted therapy, both portions==== | |
− | *[[ | ||
− | |||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
**Cycle 1: 8 mg/kg IV once on day 1 | **Cycle 1: 8 mg/kg IV once on day 1 | ||
− | ** | + | **Cycles 2 to 8: 6 mg/kg IV once on day 1 |
− | + | '''21-day cycle for 8 cycles (TH x 4; FEC & H x 4)''' | |
− | '''21-day cycle for | + | </div> |
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *HannaH: [[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | *SB3-G31-BC: [[Surgery#Breast_cancer_surgery|Surgery]], then adjuvant [[#Trastuzumab_monotherapy_2|trastuzumab]] x 30 wk | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''HannaH:''' Ismael G, Hegg R, Muehlbauer S, Heinzmann D, Lum B, Kim SB, Pienkowski T, Lichinitser M, Semiglazov V, Melichar B, Jackisch C. Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I-III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial. Lancet Oncol. 2012 Sep;13(9):869-78. Epub 2012 Aug 9. [https://doi.org/10.1016/S1470-2045(12)70329-7 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22884505/ PubMed] [https://clinicaltrials.gov/study/NCT00950300 NCT00950300] | ||
+ | ## '''Update:''' Jackisch C, Kim SB, Semiglazov V, Melichar B, Pivot X, Hillenbach C, Stroyakovskiy D, Lum BL, Elliott R, Weber HA, Ismael G. Subcutaneous versus intravenous formulation of trastuzumab for HER2-positive early breast cancer: updated results from the phase III HannaH study. Ann Oncol. 2015 Feb;26(2):320-5. Epub 2014 Nov 17. [https://doi.org/10.1093/annonc/mdu524 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25403587/ PubMed] | ||
+ | ## '''Update:''' Jackisch C, Stroyakovskiy D, Pivot X, Ahn JS, Melichar B, Chen SC, Meyenberg C, Al-Sakaff N, Heinzmann D, Hegg R. Subcutaneous vs intravenous trastuzumab for patients with ERBB2-positive early breast cancer: final analysis of the HannaH phase 3 randomized clinical trial. JAMA Oncol. 2019 May 1;5(5):e190339. Epub 2019 May 9. [https://doi.org/10.1001/jamaoncol.2019.0339 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512301/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30998824/ PubMed] | ||
+ | #'''CT-P6 3.2:''' Stebbing J, Baranau Y, Baryash V, Manikhas A, Moiseyenko V, Dzagnidze G, Zhavrid E, Boliukh D, Stroyakovskii D, Pikiel J, Eniu A, Komov D, Morar-Bolba G, Li RK, Rusyn A, Lee SJ, Lee SY, Esteva FJ. CT-P6 compared with reference trastuzumab for HER2-positive breast cancer: a randomised, double-blind, active-controlled, phase 3 equivalence trial. Lancet Oncol. 2017 Jul;18(7):917-928. Epub 2017 Jun 4. Erratum in: Lancet Oncol. 2017 Aug;18(8):e433. Erratum in: Lancet Oncol. 2017 Sep;18(9):e510. [https://doi.org/10.1016/s1470-2045(17)30434-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28592386/ PubMed] [https://clinicaltrials.gov/study/NCT02162667 NCT02162667] | ||
+ | ##'''Update:''' Esteva FJ, Baranau YV, Baryash V, Manikhas A, Moiseyenko V, Dzagnidze G, Zhavrid E, Boliukh D, Stroyakovskiy D, Pikiel J, Eniu AE, Li RK, Rusyn AV, Tiangco B, Lee SJ, Lee SY, Yu SY, Stebbing J. Efficacy and safety of CT-P6 versus reference trastuzumab in HER2-positive early breast cancer: updated results of a randomised phase 3 trial. Cancer Chemother Pharmacol. 2019 Oct;84(4):839-847. Epub 2019 Aug 19. [https://doi.org/10.1007/s00280-019-03920-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6768896/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31428820/ PubMed] | ||
+ | ##'''Update:''' Stebbing J, Baranau YV, Baryash V, Manikhas A, Moiseyenko V, Dzagnidze G, Zhavrid E, Boliukh D, Pikiel J, Eniu AE, Li RK, Tiangco B, Lee SJ, Kim S. Long-term efficacy and safety of CT-P6 versus trastuzumab in patients with HER2-positive early breast cancer: final results from a randomized phase III trial. Breast Cancer Res Treat. 2021 Aug;188(3):631-640. Epub 2021 Jun 20. [https://doi.org/10.1007/s10549-021-06240-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8272708/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34148205/ PubMed] | ||
+ | # '''SB3-G31-BC:''' Pivot X, Bondarenko I, Nowecki Z, Dvorkin M, Trishkina E, Ahn JH, Vinnyk Y, Im SA, Sarosiek T, Chatterjee S, Wojtukiewicz MZ, Moiseyenko V, Shparyk Y, Bello M 3rd, Semiglazov V, Song S, Lim J. Phase III, randomized, double-blind study comparing the efficacy, safety, and immunogenicity of SB3 (trastuzumab biosimilar) and reference trastuzumab in patients treated with neoadjuvant therapy for human epidermal growth factor receptor 2-positive early breast cancer. J Clin Oncol. 2018 Apr 1;36(10):968-974. Epub 2018 Jan 26. [https://doi.org/10.1200/JCO.2017.74.0126 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/29373094/ PubMed] [https://clinicaltrials.gov/study/NCT02149524 NCT02149524] | ||
− | ===Regimen | + | ==TH-FEC & H (Docetaxel, SC Trastuzumab) {{#subobject:ffi9f4|Regimen=1}}== |
− | {| | + | TH-FEC & H: '''<u>T</u>'''axotere (Docetaxel) & '''<u>H</u>'''erceptin Hylecta (Trastuzumab and hyaluronidase), followed by '''<u>F</u>'''luorouracil, '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''erceptin Hylecta (Trastuzumab and hyaluronidase) |
− | | | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | |[[Levels_of_Evidence#Evidence| | + | ===Regimen {{#subobject:d87acc|Variant=1}}=== |
− | | | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|Study |
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/S1470-2045(12)70329-7 Ismael et al. 2012 (HannaH)] |
− | |style="background-color:# | + | |2009-10-19 to 2010-12-01 |
− | |[[ | + | |style="background-color:#1a9851"|Phase 3 (E-RT-switch-ic) |
− | |style="background-color:# | + | |[[#TH-FEC_.26_H_.28Docetaxel.29|TH-FEC & H (IV)]] |
+ | |style="background-color:#eeee01"|Non-inferior pCR rate (co-primary endpoint) | ||
|- | |- | ||
|} | |} | ||
− | ====Chemotherapy, | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[ | + | ====Chemotherapy, T portion (cycles 1 to 4)==== |
− | *[[ | + | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 |
− | + | ====Chemotherapy, FEC portion (cycles 5 to 8)==== | |
− | + | *[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once on day 1 | |
− | + | *[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1 | |
− | + | *[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1 | |
− | *[[ | + | ====Targeted therapy, both portions (cycles 1 to 8)==== |
− | *[[ | + | *[[Trastuzumab and hyaluronidase (Herceptin Hylecta)]] 600 mg/10,000 units SC once on day 1 |
− | + | '''21-day cycle for 8 cycles (TH x 4; FEC & H x 4)''' | |
− | * | + | </div> |
− | + | <div class="toccolours" style="background-color:#cbd5e7"> | |
− | '''21-day cycle for 4 | + | ====Subsequent treatment==== |
− | + | *[[Surgery#Breast_cancer_surgery|Surgery]] | |
− | ==== | + | </div></div> |
− | *[[ | ||
− | |||
− | |||
− | |||
===References=== | ===References=== | ||
− | + | # '''HannaH:''' Ismael G, Hegg R, Muehlbauer S, Heinzmann D, Lum B, Kim SB, Pienkowski T, Lichinitser M, Semiglazov V, Melichar B, Jackisch C. Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I-III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial. Lancet Oncol. 2012 Sep;13(9):869-78. Epub 2012 Aug 9. [https://doi.org/10.1016/S1470-2045(12)70329-7 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22884505/ PubMed] [https://clinicaltrials.gov/study/NCT00950300 NCT00950300] | |
− | # | + | ## '''Update:''' Jackisch C, Kim SB, Semiglazov V, Melichar B, Pivot X, Hillenbach C, Stroyakovskiy D, Lum BL, Elliott R, Weber HA, Ismael G. Subcutaneous versus intravenous formulation of trastuzumab for HER2-positive early breast cancer: updated results from the phase III HannaH study. Ann Oncol. 2015 Feb;26(2):320-5. Epub 2014 Nov 17. [https://doi.org/10.1093/annonc/mdu524 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25403587/ PubMed] |
− | ## '''Update:''' | + | ## '''Update:''' Jackisch C, Stroyakovskiy D, Pivot X, Ahn JS, Melichar B, Chen SC, Meyenberg C, Al-Sakaff N, Heinzmann D, Hegg R. Subcutaneous vs intravenous trastuzumab for patients with ERBB2-positive early breast cancer: final analysis of the HannaH phase 3 randomized clinical trial. JAMA Oncol. 2019 May 1;5(5):e190339. Epub 2019 May 9. [https://doi.org/10.1001/jamaoncol.2019.0339 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512301/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30998824/ PubMed] |
− | # | + | ==TH-FEC & H (Paclitaxel) {{#subobject:6jga67|Regimen=1}}== |
− | + | TH-FEC & H: '''<u>T</u>'''axol (Paclitaxel) & '''<u>H</u>'''erceptin (Trastuzumab), followed by '''<u>F</u>'''luorouracil, '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''erceptin (Trastuzumab) | |
− | == | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style=" | + | ===Regimen {{#subobject:8e388e|Variant=1}}=== |
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2005.07.032 Buzdar et al. 2005] |
− | + | |2001-2003 | |
− | + | |style="background-color:#1a9851"|Phase 3 (E-esc) | |
− | + | |[[Breast_cancer,_HER2-positive_-_historical#T-FEC|T-FEC]] | |
− | + | | style="background-color:#91cf60" |Seems to have superior pCR rate (primary endpoint) | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |style="background-color:# | ||
− | |||
− | |style="background-color:# | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | ====Chemotherapy, | + | ====Chemotherapy, T portion (cycles 1 to 4)==== |
− | *[[ | + | *[[Paclitaxel (Taxol)]] 225 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1 |
− | *[[ | + | ====Chemotherapy, FEC portion (cycles 5 to 8)==== |
− | + | *[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 4 | |
− | + | *[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1 | |
− | + | *[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1 | |
− | + | ====Targeted therapy, both portions==== | |
− | *[[ | ||
− | * | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle 1: | + | **Cycle 1: 4 mg/kg IV once on day 1, '''given prior to first dose of paclitaxel''', then 2 mg/kg IV once per day on days 8 & 15 |
− | ** | + | **Cycles 2 to 8: 2 mg/kg IV once per day on days 1, 8, 15 |
+ | '''21-day cycle for 8 cycles (TH x 4; FEC & H x 4)''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # Buzdar AU, Ibrahim NK, Francis D, Booser DJ, Thomas ES, Theriault RL, Pusztai L, Green MC, Arun BK, Giordano SH, Cristofanilli M, Frye DK, Smith TL, Hunt KK, Singletary SE, Sahin AA, Ewer MS, Buchholz TA, Berry D, Hortobagyi GN. Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol. 2005 Jun 1;23(16):3676-85. Epub 2005 Feb 28. [https://doi.org/10.1200/jco.2005.07.032 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15738535/ PubMed] | ||
+ | ## '''Update:''' Buzdar AU, Valero V, Ibrahim NK, Francis D, Broglio KR, Theriault RL, Pusztai L, Green MC, Singletary SE, Hunt KK, Sahin AA, Esteva F, Symmans WF, Ewer MS, Buchholz TA, Hortobagyi GN. Neoadjuvant therapy with paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide chemotherapy and concurrent trastuzumab in human epidermal growth factor receptor 2-positive operable breast cancer: an update of the initial randomized study population and data of additional patients treated with the same regimen. Clin Cancer Res. 2007 Jan 1;13(1):228-33. [https://doi.org/10.1158/1078-0432.CCR-06-1345 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17200359/ PubMed] | ||
− | ''' | + | =Neoadjuvant therapy= |
− | + | ==Docetaxel & Trastuzumab (TH) {{#subobject:ffc0e4|Regimen=1}}== | |
− | ===Regimen #2 {{#subobject: | + | TH: '''<u>T</u>'''axotere (Docetaxel) & '''<u>H</u>'''erceptin (Trastuzumab) |
− | {| | + | <br>DH: '''<u>D</u>'''ocetaxel & '''<u>H</u>'''erceptin (Trastuzumab) |
− | | | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | |[[Levels_of_Evidence#Evidence| | + | ===Regimen variant #1, 75 mg/m<sup>2</sup> q3wk docetaxel, q3wk trastuzumab {{#subobject:3657g3|Variant=1}}=== |
− | | | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|Study |
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https://www.ncbi.nlm.nih.gov/pmc/articles/ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6813591/ Shao et al. 2020 (PEONY)] |
− | |style="background-color:# | + | |2016-03-14 to 2017-03-13 |
− | + | |style="background-color:#1a9851"|Phase 3 (C) | |
− | |style="background-color:# | + | |[[#THP_.28Docetaxel.29|THP]] |
+ | | style="background-color:#d73027" |Inferior pCR rate | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | ====Chemotherapy | + | ====Chemotherapy==== |
− | *[[ | + | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 |
− | + | ====Targeted therapy==== | |
− | |||
− | |||
− | |||
− | ==== | ||
− | |||
− | |||
− | |||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
**Cycle 1: 8 mg/kg IV once on day 1 | **Cycle 1: 8 mg/kg IV once on day 1 | ||
− | ** | + | **Cycles 2 to 4: 6 mg/kg IV once on day 1 |
− | + | '''21-day cycle for 4 cycles''' | |
− | '''21-day cycle for | + | </div> |
− | + | <div class="toccolours" style="background-color:#cbd5e7"> | |
− | ===Regimen # | + | ====Subsequent treatment==== |
− | {| | + | *[[Surgery#Breast_cancer_surgery|Surgery]], then adjuvant [[#FEC|FEC]], then adjuvant [[#Trastuzumab_monotherapy_2|trastuzumab]] |
− | | | + | </div></div><br> |
− | |[[Levels_of_Evidence#Evidence| | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | | | + | ===Regimen variant #2, 75->100 mg/m<sup>2</sup> q3wk docetaxel, q3wk trastuzumab {{#subobject:3675u3|Variant=1}}=== |
− | |[[Levels_of_Evidence#Efficacy| | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |rowspan=3|[https://doi.org/10.1016/S1470-2045(11)70336-9 Gianni et al. 2011 (NeoSphere)] | ||
+ | |rowspan=3|2007-2009 | ||
+ | |rowspan=3 style="background-color:#1a9851"|Randomized Phase 2 (C) | ||
+ | |1. [[Stub#Docetaxel_.26_Pertuzumab|Docetaxel & Pertuzumab]] | ||
+ | |style="background-color:#d3d3d3"|Not reported | ||
|- | |- | ||
− | |[ | + | |2. [[#Pertuzumab_.26_Trastuzumab_999|Pertuzumab & Trastuzumab]] |
− | |style="background-color:# | + | |style="background-color:#d3d3d3"|Not reported |
− | | | + | |- |
− | |style="background-color:# | + | |3. [[#THP_.28Docetaxel.29|THP]] |
+ | | style="background-color:#fc8d59" |Seems to have inferior pCR rate | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''Note: Docetaxel dose was only escalated if tolerated.'' |
− | == | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | + | ====Chemotherapy==== | |
− | |||
− | |||
− | |||
− | |||
− | ====Chemotherapy | ||
*[[Docetaxel (Taxotere)]] as follows: | *[[Docetaxel (Taxotere)]] as follows: | ||
− | **Cycles | + | **Cycle 1: 75 mg/m<sup>2</sup> IV once on day 1 |
+ | **Cycles 2 to 4: 100 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
**Cycle 1: 8 mg/kg IV once on day 1 | **Cycle 1: 8 mg/kg IV once on day 1 | ||
− | ** | + | **Cycles 2 to 4: 6 mg/kg IV once on day 1 |
− | + | '''21-day cycle for 4 cycles''' | |
− | '''21-day cycle for | + | </div> |
− | + | <div class="toccolours" style="background-color:#cbd5e7"> | |
− | ===Regimen # | + | ====Subsequent treatment==== |
− | {| | + | *[[Surgery#Breast_cancer_surgery|Surgery]] |
− | | | + | </div></div><br> |
− | |[[Levels_of_Evidence#Evidence| | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | | | + | ===Regimen variant #3, 100 mg/m<sup>2</sup> q3wk docetaxel, q3wk trastuzumab {{#subobject:3619u3|Variant=1}}=== |
− | |[[Levels_of_Evidence#Efficacy| | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9795751/ Wu et al. 2022 (PHEDRA)] | ||
+ | |2018-2021 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Docetaxel_.26_Trastuzumab_.28TH.29_.26_Pyrotinib|TH & Pyrotinib]] | ||
+ | | style="background-color:#d73027" |Inferior tpCR rate | ||
|- | |- | ||
− | | | + | |} |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | |[[ | + | ====Chemotherapy==== |
− | + | *[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1 | |
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycles 2 to 4: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycle for 4 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]], then adjuvant [[#FEC|FEC]] x 3 | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #4, 100 mg/m<sup>2</sup> q3wk docetaxel, weekly trastuzumab {{#subobject:361b97|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 80%; text-align:center;" | ||
+ | !style="width: 25%"|Study | ||
+ | !style="width: 25%"|Dates of enrollment | ||
+ | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.3816/cbc.2003.n.040 Van Pelt et al. 2003] |
− | |style="background-color:# | + | |2000-2002 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
+ | |OCR: 77% | ||
|- | |- | ||
|} | |} | ||
− | ====Chemotherapy | + | ''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' |
− | *[[ | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | * | + | ====Chemotherapy==== |
− | + | *[[Docetaxel (Taxotere)]] as follows: | |
− | + | **Cycles 2 to 5: 100 mg/m<sup>2</sup> IV once on day 1 | |
− | + | ====Targeted therapy==== | |
− | ==== | ||
− | |||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
**Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15 | **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15 | ||
− | **Cycles 2 to | + | **Cycles 2 to 5: 2 mg/kg IV once per day on days 1, 8, 15 |
+ | '''21-day cycle for 5 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]], then adjuvant [[#AC-H|AC-H]] | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # Van Pelt AE, Mohsin S, Elledge RM, Hilsenbeck SG, Gutierrez MC, Lucci A Jr, Kalidas M, Granchi T, Scott BG, Allred DC, Chang JC. Neoadjuvant trastuzumab and docetaxel in breast cancer: preliminary results. Clin Breast Cancer. 2003 Dec;4(5):348-53. [https://doi.org/10.3816/cbc.2003.n.040 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/14715110/ PubMed] | ||
+ | # '''NeoSphere:''' Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, Lluch A, Staroslawska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi G, Szado T, Ratnayake J, Ross G, Valagussa P. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012 Jan;13(1):25-32. Epub 2011 Dec 6. [https://doi.org/10.1016/S1470-2045(11)70336-9 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22153890/ PubMed] [https://clinicaltrials.gov/study/NCT00545688 NCT00545688] | ||
+ | ## '''Update:''' Gianni L, Pienkowski T, Im YH, Tseng LM, Liu MC, Lluch A, Starosławska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi GV, Magazzù D, McNally V, Douthwaite H, Ross G, Valagussa P. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 2016 Jun;17(6):791-800. Epub 2016 May 11. [https://doi.org/10.1016/S1470-2045(16)00163-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27179402/ PubMed] | ||
+ | # '''PEONY:''' Shao Z, Pang D, Yang H, Li W, Wang S, Cui S, Liao N, Wang Y, Wang C, Chang YC, Wang H, Kang SY, Seo JH, Shen K, Laohawiriyakamol S, Jiang Z, Li J, Zhou J, Althaus B, Mao Y, Eng-Wong J. Efficacy, Safety, and Tolerability of Pertuzumab, Trastuzumab, and Docetaxel for Patients With Early or Locally Advanced ERBB2-Positive Breast Cancer in Asia: The PEONY Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Mar 1;6(3):e193692. Epub 2020 Mar 12. [https://doi.org/10.1001/jamaoncol.2019.3692 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6813591/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31647503/ PubMed] [https://clinicaltrials.gov/study/NCT02586025 NCT02586025] | ||
+ | ##'''Update:''' Huang L, Pang D, Yang H, Li W, Wang S, Cui S, Liao N, Wang Y, Wang C, Chang YC, Wang HC, Kang SY, Seo JH, Shen K, Laohawiriyakamol S, Jiang Z, Wang H, Lamour F, Song G, Curran M, Duan C, Lysbet de Haas S, Restuccia E, Shao Z. Neoadjuvant-adjuvant pertuzumab in HER2-positive early breast cancer: final analysis of the randomized phase III PEONY trial. Nat Commun. 2024 Mar 9;15(1):2153. [https://doi.org/10.1038/s41467-024-45591-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10925021/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/38461323/ PubMed] | ||
+ | #'''PHEDRA:''' Wu J, Jiang Z, Liu Z, Yang B, Yang H, Tang J, Wang K, Liu Y, Wang H, Fu P, Zhang S, Liu Q, Wang S, Huang J, Wang C, Wang S, Wang Y, Zhen L, Zhu X, Wu F, Lin X, Zou J. Neoadjuvant pyrotinib, trastuzumab, and docetaxel for HER2-positive breast cancer (PHEDRA): a double-blind, randomized phase 3 trial. BMC Med. 2022 Dec 27;20(1):498. [https://doi.org/10.1186/s12916-022-02708-3 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9795751/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36575513/ PubMed] [https://clinicaltrials.gov/study/NCT03588091 NCT03588091] | ||
− | ''' | + | ==Docetaxel & Trastuzumab (TH) & Pyrotinib {{#subobject:f9goe4|Regimen=1}}== |
− | + | TH & Pyrotinib: '''<u>T</u>'''axotere (Docetaxel), '''<u>H</u>'''erceptin (Trastuzumab), Pyrotinib | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen {{#subobject:ico1u3|Variant=1}}=== | |
− | ''' | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | + | !style="width: 20%"|Study | |
− | ==== | + | !style="width: 20%"|Dates of enrollment |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
− | + | !style="width: 20%"|Comparator | |
− | = | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | + | |- | |
− | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9795751/ Wu et al. 2022 (PHEDRA)] | |
− | + | |2018-2021 | |
− | + | | style="background-color:#1a9851" |Phase 3 (E-esc) | |
− | = | + | |[[#Docetaxel_.26_Trastuzumab_.28TH.29|TH]] |
− | + | | style="background-color:#1a9850" |Superior tpCR rate (primary endpoint)<br>tpCR rate: 41% vs 22% | |
|- | |- | ||
− | |||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | + | ====Chemotherapy==== | |
− | + | *[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1 | |
− | + | ====Targeted therapy==== | |
− | + | *[[Pyrotinib (Irene)]] 400 mg PO once per day | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | ====Chemotherapy | ||
− | *[[ | ||
− | |||
− | |||
− | |||
− | |||
− | ==== | ||
− | *[[ | ||
− | |||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
**Cycle 1: 8 mg/kg IV once on day 1 | **Cycle 1: 8 mg/kg IV once on day 1 | ||
− | ** | + | **Cycles 2 to 4: 6 mg/kg IV once on day 1 |
− | + | '''21-day cycle for 4 cycles''' | |
− | + | </div> | |
− | + | <div class="toccolours" style="background-color:#cbd5e7"> | |
− | + | ====Subsequent treatment==== | |
− | '''21-day cycle for | + | *[[Surgery#Breast_cancer_surgery|Surgery]], then adjuvant [[#FEC|FEC]] |
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # | + | #'''PHEDRA:''' Wu J, Jiang Z, Liu Z, Yang B, Yang H, Tang J, Wang K, Liu Y, Wang H, Fu P, Zhang S, Liu Q, Wang S, Huang J, Wang C, Wang S, Wang Y, Zhen L, Zhu X, Wu F, Lin X, Zou J. Neoadjuvant pyrotinib, trastuzumab, and docetaxel for HER2-positive breast cancer (PHEDRA): a double-blind, randomized phase 3 trial. BMC Med. 2022 Dec 27;20(1):498. [https://doi.org/10.1186/s12916-022-02708-3 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9795751/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36575513/ PubMed] [https://clinicaltrials.gov/study/NCT03588091 NCT03588091] |
− | + | ==Lapatinib & Paclitaxel (TL) {{#subobject:af5af0|Regimen=1}}== | |
− | == | + | TL: '''<u>T</u>'''axol (Paclitaxel) & '''<u>L</u>'''apatinib |
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #1, weekly paclitaxel x 12 {{#subobject:bed34f|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S0140-6736(11)61847-3 Baselga et al. 2012 (NeoALTTO)] | ||
+ | |2008-2010 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-switch-ic) | ||
+ | |[[Complex_multipart_regimens#NeoALTTO|See link]] | ||
+ | |[[Complex_multipart_regimens#NeoALTTO|See link]] | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
− | ===Regimen # | + | ====Preceding treatment==== |
− | {| | + | *Neoadjuvant [[#Lapatinib_monotherapy_999|Lapatinib]] x 6 wk |
− | | | + | </div> |
− | |[[Levels_of_Evidence#Evidence| | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | | | + | ====Chemotherapy==== |
− | |[[Levels_of_Evidence# | + | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22 |
− | |- | + | ====Targeted therapy==== |
− | |[https://www.ncbi.nlm.nih.gov/pmc/articles/ | + | *[[Lapatinib (Tykerb)]] 1500 mg PO once per day |
− | |style="background-color:# | + | '''28-day cycle for 3 cycles''' |
− | + | </div> | |
− | |style="background-color:# | + | <div class="toccolours" style="background-color:#cbd5e7"> |
+ | ====Subsequent treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]], then adjuvant [[Breast_cancer#FEC_2|FEC]] x 3 | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, weekly paclitaxel x 16 {{#subobject:8aae8f|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4980567/ Carey et al. 2015 (CALGB 40601)] | ||
+ | |rowspan=2|2008-2012 | ||
+ | |rowspan=2 style="background-color:#1a9851"|Phase 3 (E-switch-ic) | ||
+ | |1. [[#Paclitaxel_.26_Trastuzumab_.28TH.29|TH]] | ||
+ | | style="background-color:#d3d3d3" |Not reported | ||
+ | |- | ||
+ | |2. [[#THL_.28Paclitaxel.29|THL]] | ||
+ | | style="background-color:#d3d3d3" |Not reported | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''Note: this arm was closed early.'' |
− | ====Chemotherapy | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[ | + | ====Chemotherapy==== |
− | *[[ | + | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22 |
− | + | ====Targeted therapy==== | |
− | ''' | + | *[[Lapatinib (Tykerb)]] 1500 mg PO once per day |
− | + | '''28-day cycle for 4 cycles''' | |
− | ==== | + | </div> |
− | *[[ | + | <div class="toccolours" style="background-color:#cbd5e7"> |
− | + | ====Subsequent treatment==== | |
− | + | *[[Surgery#Breast_cancer_surgery|Surgery]]; adjuvant [[Breast_cancer#Cyclophosphamide_.26_Doxorubicin_.28AC.29_2|AC]] x 4 or [[Breast_cancer#Dose-dense_Cyclophosphamide_.26_Doxorubicin_.28ddAC.29_2|ddAC]] x 4, then [[#Trastuzumab_monotherapy_2|trastuzumab]] for 36 weeks was recommended but not mandated | |
− | + | </div></div> | |
− | + | ===References=== | |
− | + | # '''NeoALTTO:''' Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. [https://doi.org/10.1016/S0140-6736(11)61847-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705192/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22257673/ PubMed] [https://clinicaltrials.gov/study/NCT00553358 NCT00553358] | |
− | + | ## '''Update:''' de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. Epub 2014 Aug 14. [https://doi.org/10.1016/S1470-2045(14)70320-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25130998/ PubMed] | |
− | + | ## '''Update:''' Huober J, Holmes E, Baselga J, de Azambuja E, Untch M, Fumagalli D, Sarp S, Lang I, Smith I, Boyle F, Xu B, Lecocq C, Wildiers H, Jouannaud C, Hackman J, Dasappa L, Ciruelos E, Toral Pena JC, Adamchuk H, Hickish T, de la Pena L, Jackisch C, Gelber RD, Piccart-Gebhart M, Di Cosimo S. Survival outcomes of the NeoALTTO study (BIG 1-06): updated results of a randomised multicenter phase III neoadjuvant clinical trial in patients with HER2-positive primary breast cancer. Eur J Cancer. 2019 Sep;118:169-177. Epub 2019 Aug 1. [https://doi.org/10.1016/j.ejca.2019.04.038 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31377477/ PubMed] | |
− | + | # '''CALGB 40601:''' Carey LA, Berry DA, Cirrincione CT, Barry WT, Pitcher BN, Harris LN, Ollila DW, Krop IE, Henry NL, Weckstein DJ, Anders CK, Singh B, Hoadley KA, Iglesia M, Cheang MC, Perou CM, Winer EP, Hudis CA. Molecular heterogeneity and response to neoadjuvant human epidermal growth factor receptor 2 targeting in CALGB 40601, a randomized phase III trial of paclitaxel plus trastuzumab with or without lapatinib. J Clin Oncol. 2016 Feb 20;34(6):542-9. Epub 2015 Nov 2. [https://doi.org/10.1200/JCO.2015.62.1268 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4980567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26527775/ PubMed] [https://clinicaltrials.gov/study/NCT00770809 NCT00770809] | |
− | ''' | + | ##'''Update:''' Fernandez-Martinez A, Krop IE, Hillman DW, Polley MY, Parker JS, Huebner L, Hoadley KA, Shepherd J, Tolaney S, Henry NL, Dang C, Harris L, Berry D, Hahn O, Hudis C, Winer E, Partridge A, Perou CM, Carey LA. Survival, Pathologic Response, and Genomics in CALGB 40601 (Alliance), a Neoadjuvant Phase III Trial of Paclitaxel-Trastuzumab With or Without Lapatinib in HER2-Positive Breast Cancer. J Clin Oncol. 2020 Dec 10;38(35):4184-4193. Epub 2020 Oct 23. [https://doi.org/10.1200/jco.20.01276 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723687/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33095682/ PubMed] |
− | + | ==Lapatinib & Trastuzumab {{#subobject:9cbcb2|Regimen=1}}== | |
− | ===Regimen | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| | + | ===Regimen {{#subobject:9ac66b|Variant=1}}=== |
− | | | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Study |
− | | | + | !style="width: 20%"|Dates of enrollment |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S0140-6736(11)61847-3 Baselga et al. 2012 (NeoALTTO)] |
− | |style="background-color:# | + | |2008-2010 |
− | + | |style="background-color:#1a9851"|Phase 3 (E-esc) | |
− | + | |[[Complex_multipart_regimens#NeoALTTO|See link]] | |
+ | |[[Complex_multipart_regimens#NeoALTTO|See link]] | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' |
− | ====Chemotherapy | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[ | + | ====Targeted therapy==== |
− | *[[ | + | *[[Lapatinib (Tykerb)]] 1000 mg PO once per day |
− | + | *[[Trastuzumab (Herceptin)]] 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22, 29, 36 | |
− | '''21-day cycle for | + | '''6-week course''' |
− | + | </div> | |
− | ==== | + | <div class="toccolours" style="background-color:#cbd5e7"> |
− | *[[ | + | ====Subsequent treatment==== |
− | + | *Neoadjuvant [[#THL_.28Paclitaxel.29|THL (Taxol)]] x 12 wk, then [[Surgery#Breast_cancer_surgery|surgery]] | |
− | + | </div></div> | |
+ | ===References=== | ||
+ | # '''NeoALTTO:''' Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. [https://doi.org/10.1016/S0140-6736(11)61847-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705192/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22257673/ PubMed] [https://clinicaltrials.gov/study/NCT00553358 NCT00553358] | ||
+ | ## '''Update:''' de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. Epub 2014 Aug 14. [https://doi.org/10.1016/S1470-2045(14)70320-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25130998/ PubMed] | ||
+ | ## '''Update:''' Huober J, Holmes E, Baselga J, de Azambuja E, Untch M, Fumagalli D, Sarp S, Lang I, Smith I, Boyle F, Xu B, Lecocq C, Wildiers H, Jouannaud C, Hackman J, Dasappa L, Ciruelos E, Toral Pena JC, Adamchuk H, Hickish T, de la Pena L, Jackisch C, Gelber RD, Piccart-Gebhart M, Di Cosimo S. Survival outcomes of the NeoALTTO study (BIG 1-06): updated results of a randomised multicenter phase III neoadjuvant clinical trial in patients with HER2-positive primary breast cancer. Eur J Cancer. 2019 Sep;118:169-177. Epub 2019 Aug 1. [https://doi.org/10.1016/j.ejca.2019.04.038 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31377477/ PubMed] | ||
+ | ==TCH (Docetaxel) {{#subobject:abdoj1|Regimen=1}}== | ||
+ | TCH: '''<u>T</u>'''axotere (Docetaxel), '''<u>C</u>'''arboplatin, '''<u>H</u>'''erceptin (Trastuzumab) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:adchj1|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6068194/ Lammers et al. 2018 (REFLECTIONS B327-04)] | ||
+ | |Not reported | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#TCH_.28Docetaxel.29_.28trastuzumab-qyyp.29_333|TCH (trastuzumab-qyyp)]] x 6 | ||
+ | | style="background-color:#eeee01" |Non-inferior pharmacokinetics (primary endpoint) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given second''' | ||
+ | *[[Carboplatin (Paraplatin)]] AUC 6 IV over at least 15 minutes once on day 1, '''given third''' | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV over 90 minutes once on day 1, '''given first''' | ||
+ | **Cycles 2 to 6: 6 mg/kg IV over 30 to 90 minutes once on day 1, '''given first''' | ||
+ | '''21-day cycle for 6 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''REFLECTIONS B327-04:''' Lammers PE, Dank M, Masetti R, Abbas R, Hilton F, Coppola J, Jacobs I. Neoadjuvant PF-05280014 (a potential trastuzumab biosimilar) versus trastuzumab for operable HER2+ breast cancer. Br J Cancer. 2018 Aug;119(3):266-273. Epub 2018 Jul 13. [https://doi.org/10.1038/s41416-018-0147-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6068194/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30002437/ PubMed] [https://clinicaltrials.gov/study/NCT02187744 NCT02187744] | ||
+ | |||
+ | ==TCHP (Paclitaxel) {{#subobject:ab8cj1|Regimen=1}}== | ||
+ | TCHP: '''<u>T</u>'''axol (Paclitaxel), '''<u>C</u>'''arboplatin, '''<u>H</u>'''erceptin (Trastuzumab), '''<u>P</u>'''ertuzumab<br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, standard carboplatin {{#subobject:a0cbj1|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/s1470-2045(18)30570-9 van Ramshorst et al. 2018 (TRAIN-2)] | ||
+ | |2013-2016 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-switch-ic) | ||
+ | |[[Stub#FEC_.26_HP|FEC & HP]] x 3, then [[#TCHP_.28Paclitaxel.29|TCHP]] x 6 | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of pCR rate | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
+ | *[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
**Cycle 1: 8 mg/kg IV once on day 1 | **Cycle 1: 8 mg/kg IV once on day 1 | ||
− | ** | + | **Cycles 2 to 9: 6 mg/kg IV once on day 1 |
*[[Pertuzumab (Perjeta)]] as follows: | *[[Pertuzumab (Perjeta)]] as follows: | ||
**Cycle 1: 840 mg IV once on day 1 | **Cycle 1: 840 mg IV once on day 1 | ||
− | ** | + | **Cycles 2 to 9: 420 mg IV once on day 1 |
− | + | '''21-day cycle for 9 cycles''' | |
− | '''21-day cycle for | + | </div> |
− | + | <div class="toccolours" style="background-color:#cbd5e7"> | |
− | ===Regimen # | + | ====Subsequent treatment==== |
− | {| | + | *[[Surgery#Breast_cancer_surgery|Surgery]] |
− | | | + | </div></div><br> |
− | |[[Levels_of_Evidence#Evidence| | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | | | + | ===Regimen variant #2, split carboplatin {{#subobject:a1ibj1|Variant=1}}=== |
− | |[[Levels_of_Evidence# | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/s1470-2045(18)30570-9 van Ramshorst et al. 2018 (TRAIN-2)] |
− | |style="background-color:# | + | |2013-2016 |
− | + | |style="background-color:#1a9851"|Phase 3 (E-switch-ic) | |
− | |style="background-color:# | + | |[[Stub#FEC_.26_HP|FEC & HP]] x 3, then [[#TCHP_.28Paclitaxel.29|TCHP]] x 6 |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of pCR rate | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | ====Chemotherapy | + | ====Chemotherapy==== |
− | *[[ | + | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1 & 8 |
− | *[[ | + | *[[Carboplatin (Paraplatin)]] AUC 3 IV once per day on days 1 & 8 |
− | + | ====Targeted therapy==== | |
− | |||
− | |||
− | ==== | ||
− | |||
− | |||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
**Cycle 1: 8 mg/kg IV once on day 1 | **Cycle 1: 8 mg/kg IV once on day 1 | ||
− | ** | + | **Cycles 2 to 9: 6 mg/kg IV once on day 1 |
*[[Pertuzumab (Perjeta)]] as follows: | *[[Pertuzumab (Perjeta)]] as follows: | ||
**Cycle 1: 840 mg IV once on day 1 | **Cycle 1: 840 mg IV once on day 1 | ||
− | ** | + | **Cycles 2 to 9: 420 mg IV once on day 1 |
+ | '''21-day cycle for 9 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''TRAIN-2:''' van Ramshorst MS, van der Voort A, van Werkhoven ED, Mandjes IA, Kemper I, Dezentjé VO, Oving IM, Honkoop AH, Tick LW, van de Wouw AJ, Mandigers CM, van Warmerdam LJ, Wesseling J, Vrancken Peeters MT, Linn SC, Sonke GS; Dutch Breast Cancer Research Group. Neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2 blockade for HER2-positive breast cancer (TRAIN-2): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2018 Dec;19(12):1630-1640. Epub 2018 Nov 6. [https://doi.org/10.1016/s1470-2045(18)30570-9 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/30413379/ PubMed] [https://clinicaltrials.gov/study/NCT01996267 NCT01996267] | ||
+ | ##'''Update:''' van der Voort A, van Ramshorst MS, van Werkhoven ED, Mandjes IA, Kemper I, Vulink AJ, Oving IM, Honkoop AH, Tick LW, van de Wouw AJ, Mandigers CM, van Warmerdam LJ, Wesseling J, Vrancken Peeters MT, Linn SC, Sonke GS. Three-Year Follow-up of Neoadjuvant Chemotherapy With or Without Anthracyclines in the Presence of Dual ERBB2 Blockade in Patients With ERBB2-Positive Breast Cancer: A Secondary Analysis of the TRAIN-2 Randomized, Phase 3 Trial. JAMA Oncol. 2021 Jul 1;7(7):978-984. [https://doi.org/10.1001/jamaoncol.2021.1371 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138752/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34014249/ PubMed] | ||
− | ''' | + | ==TCHP (Docetaxel) {{#subobject:CMR1|Regimen=1}}== |
− | + | TCHP: '''<u>T</u>'''axotere (Docetaxel), '''<u>C</u>'''arboplatin, '''<u>H</u>'''erceptin (Trastuzumab), '''<u>P</u>'''ertuzumab<br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen {{#subobject:CMV1|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | == | + | !style="width: 17%"|Study |
− | {| class="wikitable" style=" | + | !style="width: 15%"|Dates of enrollment |
+ | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 17%"|Comparator | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1093/annonc/mdt182 Schneeweiss et al. 2013 (TRYPHAENA)] |
− | + | |2009-2011 | |
− | + | |style="background-color:#1a9851"|Randomized Phase 2 (E-RT-switch-ic) | |
− | + | |1. [[#FEC-THP_.28Docetaxel.29|FEC-THP]]<br>2. [[#FEC_.26_HP-THP_.28Docetaxel.29_888|FEC & HP-THP]] | |
− | + | |style="background-color:#d3d3d3"|Not reported | |
− | | | + | | style="background-color:#ffffbf" |Similar rates of LVSD (co-primary endpoint) |
− | |[[ | ||
− | | | ||
− | | | ||
|- | |- | ||
− | + | |[https://doi.org/10.1016/S1470-2045(17)30716-7 Hurvitz et al. 2017 (KRISTINE)] | |
− | | | + | |2014-06-25 to 2015-06-15 |
− | + | |style="background-color:#1a9851"|Phase 3 (C) | |
− | |style="background-color:# | + | |[[#Pertuzumab_.26_T-DM1|Pertuzumab & T-DM1]] |
− | + | | style="background-color:#1a9850" |Superior EFS<sup>1</sup> (secondary endpoint)<br>(HR 0.38, 95% CI 0.20-0.74)<br><br>Seems to have superior pCR rate (primary endpoint) | |
− | |[[# | + | | |
− | |style="background-color:# | ||
|- | |- | ||
|} | |} | ||
− | ====Chemotherapy | + | ''<sup>1</sup>Reported efficacy for KRISTINE is based on the 2019 update.'' |
− | *[[ | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[ | + | ====Chemotherapy==== |
− | + | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 | |
− | ==== | + | *[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1 |
− | + | ====Targeted therapy==== | |
− | + | *[[Trastuzumab (Herceptin)]] as follows: | |
− | ** | + | **Cycle 1: 8 mg/kg IV once on day 1 |
− | + | **Cycles 2 to 6: 6 mg/kg IV once on day 1 | |
− | + | *[[Pertuzumab (Perjeta)]] as follows: | |
− | ''' | + | **Cycle 1: 840 mg IV once on day 1 |
− | + | **Cycles 2 to 6: 420 mg IV once on day 1 | |
− | + | '''21-day cycle for 6 cycles''' | |
− | + | </div> | |
− | ==== | + | <div class="toccolours" style="background-color:#cbd5e7"> |
− | * | + | ====Subsequent treatment==== |
− | + | *TRYPHAENA: [[Surgery#Breast_cancer_surgery|Surgery]], then further adjuvant treatment (radiotherapy, chemotherapy, hormonal treatment) according to local guidelines (a total of 1 year of trastuzumab was given) | |
− | * | + | *KRISTINE: [[Surgery#Breast_cancer_surgery|Surgery]] |
− | + | </div></div> | |
− | |||
===References=== | ===References=== | ||
− | # | + | # '''TRYPHAENA:''' Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, Tausch C, Seo JH, Tsai YF, Ratnayake J, McNally V, Ross G, Cortés J. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013 Sep;24(9):2278-84. Epub 2013 May 22. [https://doi.org/10.1093/annonc/mdt182 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23704196/ PubMed] [https://clinicaltrials.gov/study/NCT00976989 NCT00976989] |
− | ## '''Update:''' | + | ##'''Update:''' Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Waldron-Lynch M, Eng-Wong J, Kirk S, Cortés J. Long-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: Evaluating pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer. Eur J Cancer. 2018 Jan;89:27-35. Epub 2017 Dec 8. [https://doi.org/10.1016/j.ejca.2017.10.021 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29223479/ PubMed] |
+ | # '''KRISTINE:''' Hurvitz SA, Martin M, Symmans WF, Jung KH, Huang CS, Thompson AM, Harbeck N, Valero V, Stroyakovskiy D, Wildiers H, Campone M, Boileau JF, Beckmann MW, Afenjar K, Fresco R, Helms HJ, Xu J, Lin YG, Sparano J, Slamon D. Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2018 Jan;19(1):115-126. Epub 2017 Nov 23. [https://doi.org/10.1016/S1470-2045(17)30716-7 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/29175149/ PubMed] [https://clinicaltrials.gov/study/NCT02131064 NCT02131064] | ||
+ | ## '''Update:''' Hurvitz SA, Martin M, Jung KH, Huang CS, Harbeck N, Valero V, Stroyakovskiy D, Wildiers H, Campone M, Boileau JF, Fasching PA, Afenjar K, Spera G, Lopez-Valverde V, Song C, Trask P, Boulet T, Sparano JA, Symmans WF, Thompson AM, Slamon D. Neoadjuvant trastuzumab emtansine and pertuzumab in human epidermal growth factor receptor 2-positive breast cancer: three-year outcomes from the phase III KRISTINE Study. J Clin Oncol. 2019 Sep 1;37(25):2206-2216. Epub 2019 Jun 3. [https://doi.org/10.1200/JCO.19.00882 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774816/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31157583/ PubMed] | ||
− | == | + | ==TCHP (Docetaxel, SC Trastuzumab) {{#subobject:uhcc23|Regimen=1}}== |
− | {| class="wikitable" style=" | + | TCHP: '''<u>T</u>'''axotere (Docetaxel), '''<u>C</u>'''arboplatin, '''<u>H</u>'''erceptin Hylecta (SC Trastuzumab), '''<u>P</u>'''ertuzumab<br> |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:jcekc2|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/s1470-2045(21)00122-4 Pérez-García et al. 2021 (PHERGain)] |
− | + | |2017-06-26 to 2019-04-24 | |
− | + | | style="background-color:#1a9851" |Randomized Phase 2 (C) | |
− | + | |[[#Pertuzumab_.26_Trastuzumab_.28HP.2F_SC Trastuzumab.29_888|HP]], then PET-adapted therapy | |
− | + | | style="background-color:#d3d3d3" |Non-comparative | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |style="background-color:# | ||
− | |||
− | |style="background-color:# | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | ====Chemotherapy | + | ====Chemotherapy==== |
− | *[[ | + | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 |
− | *[[ | + | *[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1 |
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab and hyaluronidase (Herceptin Hylecta)]] 600 mg SC once on day 1 | ||
+ | *[[Pertuzumab (Perjeta)]] as follows: | ||
+ | **Cycle 1: 840 mg IV once on day 1 | ||
+ | **Cycles 2 to 6: 420 mg IV once on day 1 | ||
+ | '''21-day cycle for 6 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''PHERGain:''' Pérez-García JM, Gebhart G, Ruiz Borrego M, Stradella A, Bermejo B, Schmid P, Marmé F, Escrivá-de-Romani S, Calvo L, Ribelles N, Martinez N, Albacar C, Prat A, Dalenc F, Kerrou K, Colleoni M, Afonso N, Di Cosimo S, Sampayo-Cordero M, Malfettone A, Cortés J, Llombart-Cussac A; PHERGain steering committee and trial investigators. Chemotherapy de-escalation using an 18F-FDG-PET-based pathological response-adapted strategy in patients with HER2-positive early breast cancer (PHERGain): a multicentre, randomised, open-label, non-comparative, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):858-871. Epub 2021 May 18. [https://doi.org/10.1016/s1470-2045(21)00122-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34019819/ PubMed] [https://clinicaltrials.gov/study/NCT03161353 NCT03161353] | ||
+ | ##'''Update:''' Pérez-García JM, Cortés J, Ruiz-Borrego M, Colleoni M, Stradella A, Bermejo B, Dalenc F, Escrivá-de-Romaní S, Calvo Martínez L, Ribelles N, Marmé F, Cortés A, Albacar C, Gebhart G, Prat A, Kerrou K, Schmid P, Braga S, Di Cosimo S, Gion M, Antonarelli G, Popa C, Szostak E, Alcalá-López D, Gener P, Rodríguez-Morató J, Mina L, Sampayo-Cordero M, Llombart-Cussac A; PHERGain Trial Investigators. 3-year invasive disease-free survival with chemotherapy de-escalation using an 18F-FDG-PET-based, pathological complete response-adapted strategy in HER2-positive early breast cancer (PHERGain): a randomised, open-label, phase 2 trial. Lancet. 2024 Apr 27;403(10437):1649-1659. Epub 2024 Apr 3. [https://doi.org/10.1016/s0140-6736(24)00054-0 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/38582092/ PubMed] | ||
− | ==== | + | ==Paclitaxel & Trastuzumab (TH) {{#subobject:647f67|Regimen=1}}== |
− | * | + | TH: '''<u>T</u>'''axol (Paclitaxel) & '''<u>H</u>'''erceptin (Trastuzumab) |
− | + | <br>T-T: '''<u>T</u>'''axol (Paclitaxel) & '''<u>T</u>'''rastuzumab | |
− | ''' | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | + | ===Regimen variant #1, weekly paclitaxel x 12, weekly trastuzumab {{#subobject:39d2af|Variant=1}}=== | |
− | ====Chemotherapy | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | *[[Paclitaxel (Taxol)]] | + | !style="width: 20%"|Study |
− | + | !style="width: 20%"|Dates of enrollment | |
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S0140-6736(11)61847-3 Baselga et al. 2012 (NeoALTTO)] | ||
+ | |2008-2010 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[Complex_multipart_regimens#NeoALTTO|See link]] | ||
+ | |[[Complex_multipart_regimens#NeoALTTO|See link]] | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. Patients in NeoALTTO had already undergone trastuzumab loading so would continue at the 2 mg/kg weekly dose.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *NeoALTTO: Neoadjvuant [[#Trastuzumab_monotherapy|Trastuzumab]] x 6 wk | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15 | ||
+ | **Cycles 2 to 4: 2 mg/kg IV once per day on days 1, 8, 15 | ||
+ | '''21-day cycle for 4 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *NeoALTTO: [[Surgery#Breast_cancer_surgery|Surgery]], then adjuvant [[Breast_cancer#FEC_2|FEC]] x 3 | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, weekly paclitaxel x 12, q3wk trastuzumab {{#subobject:b061d7|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S1470-2045(18)30241-9 von Minckwitz et al. 2018 (LILAC)] | ||
+ | |2013-2015 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#Paclitaxel_.26_Trastuzumab-anns_888|Paclitaxel & Trastuzumab-anns]] | ||
+ | |style="background-color:#ffffbf"|Inconclusive whether equivalent pCR rate | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *Neoadjuvant [[Regimen_classes#Anthracycline-based_regimen|anthracycline-containing chemotherapy]] x 4 | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | ||
+ | ====Targeted therapy==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
**Cycle 1: 8 mg/kg IV once on day 1 | **Cycle 1: 8 mg/kg IV once on day 1 | ||
− | ** | + | **Cycles 2 to 4: 6 mg/kg IV once on day 1 |
− | + | '''21-day cycle for 4 cycles''' | |
− | '''21-day cycle for | + | </div> |
− | + | <div class="toccolours" style="background-color:#cbd5e7"> | |
− | ===Regimen # | + | ====Subsequent treatment==== |
− | {| | + | *[[Surgery#Breast_cancer_surgery|Surgery]] |
− | | | + | </div></div><br> |
− | |[[Levels_of_Evidence#Evidence| | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #3, weekly paclitaxel x 16 {{#subobject:068233|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4980567/ Carey et al. 2015 (CALGB 40601)] | ||
+ | |rowspan=2|2008-2012 | ||
+ | |rowspan=2 style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1. [[#THL_.28Paclitaxel.29|THL]] | ||
+ | |style="background-color:#ffffbf"|Did not meet primary endpoint of pCR rate | ||
|- | |- | ||
− | |[ | + | |2. [[#Lapatinib_.26_Paclitaxel_.28TL.29|TL]] |
− | |style="background-color:# | + | | style="background-color:#d3d3d3" |Not reported |
|- | |- | ||
|} | |} | ||
− | ====Chemotherapy | + | ''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' |
− | *[[ | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[ | + | ====Chemotherapy==== |
− | + | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22 | |
− | ''' | + | ====Targeted therapy==== |
− | + | *[[Trastuzumab (Herceptin)]] as follows: | |
− | ====Chemotherapy | + | **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22 |
− | *[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV | + | **Cycles 2 to 4: 2 mg/kg IV once per day on days 1, 8, 15, 22 |
+ | '''28-day cycle for 4 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]], then adjuvant [[Breast_cancer#Cyclophosphamide_.26_Doxorubicin_.28AC.29_2|AC]] x 4 or [[Breast_cancer#Dose-dense_Cyclophosphamide_.26_Doxorubicin_.28ddAC.29_2|ddAC]] x 4, then [[#Trastuzumab_monotherapy_2|trastuzumab]] for 36 weeks was recommended but not mandated | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #4, q3wk, paclitaxel 175 mg/m<sup>2</sup> {{#subobject:7573a9|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S1470-2045(18)30241-9 von Minckwitz et al. 2018 (LILAC)] | ||
+ | |2013-2015 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#Paclitaxel_.26_Trastuzumab-anns_888|Paclitaxel & Trastuzumab-anns]] | ||
+ | |style="background-color:#ffffbf"|Inconclusive whether equivalent pCR rate | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *Neoadjuvant [[Regimen_classes#Anthracycline-based_regimen|anthracycline-containing chemotherapy]] x 4 | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle 1: | + | **Cycle 1: 8 mg/kg IV once |
− | **Cycles 2 to 4: | + | **Cycles 2 to 4: 6 mg/kg IV once on day 1 |
− | + | '''21-day cycle for 4 cycles''' | |
− | ''' | + | </div> |
− | + | <div class="toccolours" style="background-color:#cbd5e7"> | |
− | + | ====Subsequent treatment==== | |
− | + | *[[Surgery#Breast_cancer_surgery|Surgery]] | |
− | + | </div></div> | |
− | ==== | ||
− | |||
− | |||
− | |||
− | |||
− | |||
===References=== | ===References=== | ||
− | # | + | # '''NeoALTTO:''' Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. [https://doi.org/10.1016/S0140-6736(11)61847-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705192/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22257673/ PubMed] [https://clinicaltrials.gov/study/NCT00553358 NCT00553358] |
− | # | + | ## '''Update:''' de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. Epub 2014 Aug 14. [https://doi.org/10.1016/S1470-2045(14)70320-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25130998/ PubMed] |
+ | ## '''Update:''' Huober J, Holmes E, Baselga J, de Azambuja E, Untch M, Fumagalli D, Sarp S, Lang I, Smith I, Boyle F, Xu B, Lecocq C, Wildiers H, Jouannaud C, Hackman J, Dasappa L, Ciruelos E, Toral Pena JC, Adamchuk H, Hickish T, de la Pena L, Jackisch C, Gelber RD, Piccart-Gebhart M, Di Cosimo S. Survival outcomes of the NeoALTTO study (BIG 1-06): updated results of a randomised multicenter phase III neoadjuvant clinical trial in patients with HER2-positive primary breast cancer. Eur J Cancer. 2019 Sep;118:169-177. Epub 2019 Aug 1. [https://doi.org/10.1016/j.ejca.2019.04.038 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31377477/ PubMed] | ||
+ | # '''CALGB 40601:''' Carey LA, Berry DA, Cirrincione CT, Barry WT, Pitcher BN, Harris LN, Ollila DW, Krop IE, Henry NL, Weckstein DJ, Anders CK, Singh B, Hoadley KA, Iglesia M, Cheang MC, Perou CM, Winer EP, Hudis CA. Molecular heterogeneity and response to neoadjuvant human epidermal growth factor receptor 2 targeting in CALGB 40601, a randomized phase III trial of paclitaxel plus trastuzumab with or without lapatinib. J Clin Oncol. 2016 Feb 20;34(6):542-9. Epub 2015 Nov 2. [https://doi.org/10.1200/JCO.2015.62.1268 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4980567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26527775/ PubMed] [https://clinicaltrials.gov/study/NCT00770809 NCT00770809] | ||
+ | ##'''Update:''' Fernandez-Martinez A, Krop IE, Hillman DW, Polley MY, Parker JS, Huebner L, Hoadley KA, Shepherd J, Tolaney S, Henry NL, Dang C, Harris L, Berry D, Hahn O, Hudis C, Winer E, Partridge A, Perou CM, Carey LA. Survival, Pathologic Response, and Genomics in CALGB 40601 (Alliance), a Neoadjuvant Phase III Trial of Paclitaxel-Trastuzumab With or Without Lapatinib in HER2-Positive Breast Cancer. J Clin Oncol. 2020 Dec 10;38(35):4184-4193. Epub 2020 Oct 23. [https://doi.org/10.1200/jco.20.01276 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723687/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33095682/ PubMed] | ||
+ | <!-- Presented in part by Dr. Park at the 104th annual meeting of the American Association for Cancer Research, Washington, DC, April 6–10, 2013. --> | ||
+ | # '''I-SPY 2 neratinib:''' Park JW, Liu MC, Yee D, Yau C, van 't Veer LJ, Symmans WF, Paoloni M, Perlmutter J, Hylton NM, Hogarth M, DeMichele A, Buxton MB, Chien AJ, Wallace AM, Boughey JC, Haddad TC, Chui SY, Kemmer KA, Kaplan HG, Isaacs C, Nanda R, Tripathy D, Albain KS, Edmiston KK, Elias AD, Northfelt DW, Pusztai L, Moulder SL, Lang JE, Viscusi RK, Euhus DM, Haley BB, Khan QJ, Wood WC, Melisko M, Schwab R, Helsten T, Lyandres J, Davis SE, Hirst GL, Sanil A, Esserman LJ, Berry DA; I-SPY 2 Investigators. Adaptive randomization of neratinib in early breast cancer. N Engl J Med. 2016 Jul 7;375(1):11-22. [https://doi.org/10.1056/NEJMoa1513750 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259558/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27406346/ PubMed] [https://clinicaltrials.gov/study/NCT01042379 NCT01042379] | ||
+ | # '''LILAC:''' von Minckwitz G, Colleoni M, Kolberg HC, Morales S, Santi P, Tomasevic Z, Zhang N, Hanes V. Efficacy and safety of ABP 980 compared with reference trastuzumab in women with HER2-positive early breast cancer (LILAC study): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2018 Jul;19(7):987-998. Epub 2018 Jun 4. [https://doi.org/10.1016/S1470-2045(18)30241-9 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/29880292/ PubMed] [https://clinicaltrials.gov/study/NCT01901146 NCT01901146] | ||
− | == | + | ==THL (Paclitaxel) {{#subobject:6992f4|Regimen=1}}== |
− | {| class="wikitable" style=" | + | THL: '''<u>T</u>'''axol (Paclitaxel), '''<u>H</u>'''erceptin (Trastuzumab), '''<u>L</u>'''apatinib |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, weekly paclitaxel x 12 {{#subobject:459c75|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S0140-6736(11)61847-3 Baselga et al. 2012 (NeoALTTO)] | ||
+ | |2008-2010 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |[[Complex_multipart_regimens#NeoALTTO|See link]] | ||
+ | |[[Complex_multipart_regimens#NeoALTTO|See link]] | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
− | ===Regimen # | + | ====Preceding treatment==== |
− | {| | + | *Neoadjuvant [[#Lapatinib_.26_Trastuzumab|Lapatinib & Trastuzumab]] x 6 wk |
− | | | + | </div> |
− | |[[Levels_of_Evidence#Evidence| | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | | | + | ====Chemotherapy==== |
− | |[[Levels_of_Evidence# | + | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22 |
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] 2 mg/kg IV once per day on days 1, 8, 15, 22 | ||
+ | *[[Lapatinib (Tykerb)]] 1000 mg PO once per day | ||
+ | '''28-day cycle for 3 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]], then adjuvant [[Breast_cancer#FEC_2|FEC]] x 3 | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, weekly paclitaxel x 16 {{#subobject:1b4c0a|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https://www.ncbi.nlm.nih.gov/pmc/articles/ | + | |rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4980567/ Carey et al. 2015 (CALGB 40601)] |
− | |style="background-color:# | + | |rowspan=2|2008-2012 |
− | + | |rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc) | |
− | |style="background-color:# | + | |1. [[#Paclitaxel_.26_Trastuzumab_.28TH.29|TH]] |
+ | |style="background-color:#ffffbf"|Did not meet primary endpoint of pCR rate | ||
+ | |- | ||
+ | |2. [[#Lapatinib_.26_Paclitaxel_.28TL.29|TL]] | ||
+ | | style="background-color:#d3d3d3" |Not reported | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | ====Chemotherapy | + | ====Chemotherapy==== |
− | *[[ | + | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22 |
− | *[[ | + | ====Targeted therapy==== |
− | + | *[[Trastuzumab (Herceptin)]] as follows: | |
− | ==== | + | **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22 |
− | *G- | + | **Cycles 2 to 4: 2 mg/kg IV once per day on days 1, 8, 15, 22 |
− | + | *[[Lapatinib (Tykerb)]] 750 mg PO once per day | |
− | ''' | + | '''28-day cycle for 4 cycles''' |
− | + | </div> | |
− | ==== | + | <div class="toccolours" style="background-color:#cbd5e7"> |
− | + | ====Subsequent treatment==== | |
− | + | *[[Surgery#Breast_cancer_surgery|Surgery]]; adjuvant [[Breast_cancer#Cyclophosphamide_.26_Doxorubicin_.28AC.29_2|AC]] x 4 or [[Breast_cancer#Dose-dense_Cyclophosphamide_.26_Doxorubicin_.28ddAC.29_2|ddAC]] x 4, then [[#Trastuzumab_monotherapy_2|trastuzumab]] for 36 weeks was recommended but not mandated | |
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''NeoALTTO:''' Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. [https://doi.org/10.1016/S0140-6736(11)61847-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705192/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22257673/ PubMed] [https://clinicaltrials.gov/study/NCT00553358 NCT00553358] | ||
+ | ## '''Update:''' de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. Epub 2014 Aug 14. [https://doi.org/10.1016/S1470-2045(14)70320-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25130998/ PubMed] | ||
+ | ## '''Update:''' Huober J, Holmes E, Baselga J, de Azambuja E, Untch M, Fumagalli D, Sarp S, Lang I, Smith I, Boyle F, Xu B, Lecocq C, Wildiers H, Jouannaud C, Hackman J, Dasappa L, Ciruelos E, Toral Pena JC, Adamchuk H, Hickish T, de la Pena L, Jackisch C, Gelber RD, Piccart-Gebhart M, Di Cosimo S. Survival outcomes of the NeoALTTO study (BIG 1-06): updated results of a randomised multicenter phase III neoadjuvant clinical trial in patients with HER2-positive primary breast cancer. Eur J Cancer. 2019 Sep;118:169-177. Epub 2019 Aug 1. [https://doi.org/10.1016/j.ejca.2019.04.038 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31377477/ PubMed] | ||
+ | # '''CALGB 40601:''' Carey LA, Berry DA, Cirrincione CT, Barry WT, Pitcher BN, Harris LN, Ollila DW, Krop IE, Henry NL, Weckstein DJ, Anders CK, Singh B, Hoadley KA, Iglesia M, Cheang MC, Perou CM, Winer EP, Hudis CA. Molecular heterogeneity and response to neoadjuvant human epidermal growth factor receptor 2 targeting in CALGB 40601, a randomized phase III trial of paclitaxel plus trastuzumab with or without lapatinib. J Clin Oncol. 2016 Feb 20;34(6):542-9. Epub 2015 Nov 2. [https://doi.org/10.1200/JCO.2015.62.1268 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4980567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26527775/ PubMed] [https://clinicaltrials.gov/study/NCT00770809 NCT00770809] | ||
+ | ##'''Update:''' Fernandez-Martinez A, Krop IE, Hillman DW, Polley MY, Parker JS, Huebner L, Hoadley KA, Shepherd J, Tolaney S, Henry NL, Dang C, Harris L, Berry D, Hahn O, Hudis C, Winer E, Partridge A, Perou CM, Carey LA. Survival, Pathologic Response, and Genomics in CALGB 40601 (Alliance), a Neoadjuvant Phase III Trial of Paclitaxel-Trastuzumab With or Without Lapatinib in HER2-Positive Breast Cancer. J Clin Oncol. 2020 Dec 10;38(35):4184-4193. Epub 2020 Oct 23. [https://doi.org/10.1200/jco.20.01276 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723687/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33095682/ PubMed] | ||
+ | ==THP (Docetaxel) {{#subobject:24b376|Regimen=1}}== | ||
+ | THP: '''<u>T</u>'''axotere (Docetaxel), '''<u>H</u>'''erceptin (Trastuzumab), '''<u>P</u>'''ertuzumab | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:3f1974|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |rowspan=3|[https://doi.org/10.1016/S1470-2045(11)70336-9 Gianni et al. 2011 (NeoSphere)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-2-1 <span style="color:white;">ESMO-MCBS (C)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |rowspan=3|2007-2009 | ||
+ | |rowspan=3 style="background-color:#1a9851"|Randomized Phase 2 (E-RT-esc) | ||
+ | |1. [[Stub#Docetaxel_.26_Pertuzumab|Docetaxel & Pertuzumab]] | ||
+ | |style="background-color:#ffffbf"|Did not meet primary endpoint of pCR rate | ||
+ | |- | ||
+ | |2. [[#Pertuzumab_.26_Trastuzumab_999|Pertuzumab & Trastuzumab]] | ||
+ | |style="background-color:#ffffbf"|Did not meet primary endpoint of pCR rate | ||
+ | |- | ||
+ | |3. [[#Docetaxel_.26_Trastuzumab_.28TH.29|TH]] | ||
+ | |style="background-color:#91cf60"|Seems to have superior pCR rate (primary endpoint) | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6813591/ Shao et al. 2020 (PEONY)] | ||
+ | |2016-03-14 to 2017-03-13 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |[[#Docetaxel_.26_Trastuzumab_.28TH.29|TH]] | ||
+ | | style="background-color:#1a9850" |Superior pCR rate (primary endpoint)<br><br>Superior DFS60<sup>1</sup> (secondary endpoint)<br>DFS60: 86% vs 75%<br>(HR 0.52, 95% CI 0.30-0.88) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Reported efficacy for PEONY is based on the 2024 update.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
**Cycle 1: 8 mg/kg IV once on day 1 | **Cycle 1: 8 mg/kg IV once on day 1 | ||
− | ** | + | **Cycles 2 to 4: 6 mg/kg IV once on day 1 |
+ | *[[Pertuzumab (Perjeta)]] as follows: | ||
+ | **Cycle 1: 840 mg IV once on day 1 | ||
+ | **Cycles 2 to 4: 420 mg IV once on day 1 | ||
+ | '''21-day cycle for 4 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *NeoSphere: [[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | *PEONY: [[Surgery#Breast_cancer_surgery|Surgery]], then adjuvant [[#FEC|FEC]], then adjuvant [[#Pertuzumab_.26_Trastuzumab_888|Pertuzumab & Trastuzumab]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#fff2ae"> | ||
+ | ====Dose and schedule modifications==== | ||
+ | *Based on tolerability, investigators could increase docetaxel dose to 100 mg/m<sup>2</sup> IV once on day 1 in cycles 2 to 4 | ||
+ | </div></div> | ||
− | ''' | + | ===References=== |
+ | # '''NeoSphere:''' Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, Lluch A, Staroslawska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi G, Szado T, Ratnayake J, Ross G, Valagussa P. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012 Jan;13(1):25-32. Epub 2011 Dec 6. [https://doi.org/10.1016/S1470-2045(11)70336-9 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22153890/ PubMed] [https://clinicaltrials.gov/study/NCT00545688 NCT00545688] | ||
+ | ## '''Update:''' Gianni L, Pienkowski T, Im YH, Tseng LM, Liu MC, Lluch A, Starosławska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi GV, Magazzù D, McNally V, Douthwaite H, Ross G, Valagussa P. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 2016 Jun;17(6):791-800. Epub 2016 May 11. [https://doi.org/10.1016/S1470-2045(16)00163-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27179402/ PubMed] | ||
+ | # '''PEONY:''' Shao Z, Pang D, Yang H, Li W, Wang S, Cui S, Liao N, Wang Y, Wang C, Chang YC, Wang H, Kang SY, Seo JH, Shen K, Laohawiriyakamol S, Jiang Z, Li J, Zhou J, Althaus B, Mao Y, Eng-Wong J. Efficacy, Safety, and Tolerability of Pertuzumab, Trastuzumab, and Docetaxel for Patients With Early or Locally Advanced ERBB2-Positive Breast Cancer in Asia: The PEONY Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Mar 1;6(3):e193692. Epub 2020 Mar 12. [https://doi.org/10.1001/jamaoncol.2019.3692 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6813591/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31647503/ PubMed] [https://clinicaltrials.gov/study/NCT02586025 NCT02586025] | ||
+ | ##'''Update:''' Huang L, Pang D, Yang H, Li W, Wang S, Cui S, Liao N, Wang Y, Wang C, Chang YC, Wang HC, Kang SY, Seo JH, Shen K, Laohawiriyakamol S, Jiang Z, Wang H, Lamour F, Song G, Curran M, Duan C, Lysbet de Haas S, Restuccia E, Shao Z. Neoadjuvant-adjuvant pertuzumab in HER2-positive early breast cancer: final analysis of the randomized phase III PEONY trial. Nat Commun. 2024 Mar 9;15(1):2153. [https://doi.org/10.1038/s41467-024-45591-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10925021/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/38461323/ PubMed] | ||
− | ===Regimen | + | ==Trastuzumab monotherapy {{#subobject:9cbcb2|Regimen=1}}== |
− | {| | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | | | + | ===Regimen {{#subobject:9ac66b|Variant=1}}=== |
− | |[[Levels_of_Evidence#Evidence| | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | | | + | !style="width: 20%"|Study |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|Dates of enrollment |
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S0140-6736(11)61847-3 Baselga et al. 2012 (NeoALTTO)] |
− | |style="background-color:# | + | |2008-2010 |
− | + | |style="background-color:#1a9851"|Phase 3 (C) | |
− | + | |[[Complex_multipart_regimens#NeoALTTO|See link]] | |
+ | |[[Complex_multipart_regimens#NeoALTTO|See link]] | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' |
− | ==== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[ | + | ====Targeted therapy==== |
− | *[[ | + | *[[Trastuzumab (Herceptin)]] 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22, 29, 36 |
+ | '''6-week course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *Neoadjuvant [[#Paclitaxel_.26_Trastuzumab_.28TH.29|TH (Paclitaxel)]] x 12 wk, then [[Surgery#Breast_cancer_surgery|surgery]] | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''NeoALTTO:''' Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. [https://doi.org/10.1016/S0140-6736(11)61847-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705192/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22257673/ PubMed] [https://clinicaltrials.gov/study/NCT00553358 NCT00553358] | ||
+ | ## '''Update:''' de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. Epub 2014 Aug 14. [https://doi.org/10.1016/S1470-2045(14)70320-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25130998/ PubMed] | ||
+ | ## '''Update:''' Huober J, Holmes E, Baselga J, de Azambuja E, Untch M, Fumagalli D, Sarp S, Lang I, Smith I, Boyle F, Xu B, Lecocq C, Wildiers H, Jouannaud C, Hackman J, Dasappa L, Ciruelos E, Toral Pena JC, Adamchuk H, Hickish T, de la Pena L, Jackisch C, Gelber RD, Piccart-Gebhart M, Di Cosimo S. Survival outcomes of the NeoALTTO study (BIG 1-06): updated results of a randomised multicenter phase III neoadjuvant clinical trial in patients with HER2-positive primary breast cancer. Eur J Cancer. 2019 Sep;118:169-177. Epub 2019 Aug 1. [https://doi.org/10.1016/j.ejca.2019.04.038 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31377477/ PubMed] | ||
− | ==== | + | =Neoadjuvant response criteria= |
− | * | + | ==Clinical response rate (cRR)== |
− | + | ''Although fairly dated, some trials such as [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107749/ ACOSOG Z1031] make use of the WHO criteria for response to neoadjuvant therapy. Included here primarily for historical purposes.'' | |
− | '''14- | + | </div></div> |
− | + | ===References=== | |
− | ====Chemotherapy, | + | # Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer. 1981 Jan 1;47(1):207-14. [https://doi.org/10.1002/1097-0142(19810101)47:1%3C207::AID-CNCR2820470134%3E3.0.CO;2-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7459811/ PubMed] |
− | *[[ | + | ==Miller-Payne scoring system== |
− | **Cycle 1: | + | *Grade 1: No change or some changes to individual malignant cells, but no reduction in overall cellularity |
− | * | + | *Grade 2: Minor loss of tumor cells (up to 30%), but overall cellularity still high |
+ | *Grade 3: An estimated 30 to 90% reduction in the number of tumor cells | ||
+ | *Grade 4: Marked disappearance of tumor cells such that only small clusters or widely dispersed individual cells remain (loss of greater than 90% of tumor cells) | ||
+ | *Grade 5: No invasive cancer cells identifiable in sections from the site of the tumor (carcinoma ''in situ'' may be present) | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # Ogston KN, Miller ID, Payne S, Hutcheon AW, Sarkar TK, Smith I, Schofield A, Heys SD. A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast. 2003 Oct;12(5):320-7. [https://doi.org/10.1016/s0960-9776(03)00106-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14659147/ PubMed] | ||
+ | ==Residual cancer burden (RCB)== | ||
+ | *The RCB is calculated as follows: RCB = 1.4 (''f<sub>inv</sub>*d<sub>prim</sub>'')<sup>0.17</sup> + [4(1 - 0.75<sup>''LN''</sup>)''d<sub>met</sub>'']<sup>0.17</sup> | ||
+ | **where ''d<sub>prim</sub>'' is derived from the bidimensional diameters of the primary tumor bed in the resected specimen, ''f<sub>inv</sub>'' is the proportion of the primary tumor bed that contains invasive carcinoma, ''LN'' is the number of axillary lymph nodes containing metastatic carcinoma, and ''d<sub>met</sub>'' is the diameter of the largest metastasis in an axillary lymph node. | ||
+ | **The cut-off points are 1.36 and 3.28. | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # Symmans WF, Peintinger F, Hatzis C, Rajan R, Kuerer H, Valero V, Assad L, Poniecka A, Hennessy B, Green M, Buzdar AU, Singletary SE, Hortobagyi GN, Pusztai L. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol. 2007 Oct 1;25(28):4414-22. Epub 2007 Sep 4. [https://doi.org/10.1200/JCO.2007.10.6823 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17785706/ PubMed] | ||
+ | ==Residual disease in breast and nodes (RDBN)== | ||
+ | *Level 1: pCR in breast and nodes with or without ''in situ'' carcinoma | ||
+ | *Levels 2 to 4: Residual disease, calculated as 0.2 (residual breast tumor size in cm) + index of involved nodes (0 for no positive nodes, 1 for 1 to 4 positive nodes, 2 for 5 to 7 positive nodes, and 3 for 8 positive nodes) + the Scarff–Bloom–Richardson grade (1, 2, or 3). The cut-off points are 3 and 4.3. | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # Chollet P, Abrial C, Durando X, Thivat E, Tacca O, Mouret-Reynier MA, Leheurteur M, Kwiatkowski F, Dauplat J, Penault-Llorca F. A new prognostic classification after primary chemotherapy for breast cancer: residual disease in breast and nodes (RDBN). Cancer J. 2008 Mar-Apr;14(2):128-32. [https://doi.org/10.1097/ppo.0b013e31816bdea2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18391619/ PubMed] | ||
+ | ==Sataloff's classification== | ||
+ | *Breast: | ||
+ | **T-A: Total or nearly total therapeutic effect | ||
+ | **T-B: Greater than 50% therapeutic effect | ||
+ | **T-C: Less than 50% therapeutic effect | ||
+ | **T-D: No therapeutic effect | ||
+ | *Lymph node: | ||
+ | **N-A: Therapeutic effect but no metastasis | ||
+ | **N-B: No metastasis, no therapeutic effect | ||
+ | **N-C: Therapeutic effect but metastasis | ||
+ | **N-D: Metastasis, no therapeutic effect | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # Sataloff DM, Mason BA, Prestipino AJ, Seinige UL, Lieber CP, Baloch Z. Pathologic response to induction chemotherapy in locally advanced carcinoma of the breast: a determinant of outcome. J Am Coll Surg. 1995 Mar;180(3):297-306. [https://pubmed.ncbi.nlm.nih.gov/7874340/ PubMed] | ||
+ | ==Tumor response ratio== | ||
+ | Calculated as follows: Residual breast disease observed upon pathologic examination divided by the size of the tumor on the pre-neoadjuvant therapy image. | ||
+ | *TRR = 0: pathologic complete response (pCR) | ||
+ | *TRR greater than 0 up to 0.4: strong partial response | ||
+ | *TRR greater than 0.4 up to 1.0: weak partial response (WPR) | ||
+ | *TRR greater than 1.0: tumor growth | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # Miller M, Ottesen RA, Niland JC, Kruper L, Chen SL, Vito C. Tumor response ratio predicts overall survival in breast cancer patients treated with neoadjuvant chemotherapy. Ann Surg Oncol. 2014 Oct;21(10):3317-23. Epub 2014 Jul 25. [https://doi.org/10.1245/s10434-014-3922-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25059788/ PubMed] | ||
+ | ==ypTNM staging== | ||
+ | This system is proprietary to the AJCC. Please [https://cancerstaging.org/Pages/default.aspx visit their site] or consult the AJCC Manual for further details. | ||
+ | =Adjuvant therapy, sequential regimens= | ||
+ | ==AC-H {{#subobject:77b0fd|Regimen=1}}== | ||
+ | AC-H: '''<u>A</u>'''driamycin (Doxorubicin) and '''<u>C</u>'''yclophosphamide, followed by '''<u>H</u>'''erceptin (Trastuzumab) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1 {{#subobject:1ec4b2|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.20.00184 Sawaki et al. 2020 (RESPECT)] | ||
+ | |2009-10 to 2014-11 | ||
+ | | style="background-color:#1a9851" |Randomized (C) | ||
+ | |[[#Trastuzumab_monotherapy_2|Trastuzumab]] x 1 y | ||
+ | | style="background-color:#ffffbf" |Inconclusive whether non-inferior DFS (primary endpoint) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, AC portion (cycles 1 to 4)==== | ||
+ | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, H portion (cycles 5 to 22)==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 5: 8 mg/kg IV once on day 1 | ||
+ | **Cycles 6 to 22: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycle for 22 cycles (AC x 4; H x 18)''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, weekly trastuzumab {{#subobject:ac3513|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.3816/cbc.2003.n.040 Van Pelt et al. 2003] | ||
+ | |2000-2002 | ||
+ | | style="background-color:#91cf61" |Phase 2 | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *Neoadjuvant [[#Docetaxel_.26_Trastuzumab_.28TH.29|TH]], then [[Surgery#Breast_cancer_surgery|surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, AC portion (cycles 1 to 4)==== | ||
+ | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, H portion (cycles 5 to 56)==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 4 mg/kg IV once on day 1 |
− | ** | + | **Cycles 6 to 56: 2 mg/kg IV once on day 1 |
− | + | '''21-day cycle for 4 cycles, then 7-day cycle for 52 cycles (AC x 4; H x 52)''' | |
− | '''21-day cycle for | + | </div></div> |
+ | ===References=== | ||
+ | # Van Pelt AE, Mohsin S, Elledge RM, Hilsenbeck SG, Gutierrez MC, Lucci A Jr, Kalidas M, Granchi T, Scott BG, Allred DC, Chang JC. Neoadjuvant trastuzumab and docetaxel in breast cancer: preliminary results. Clin Breast Cancer. 2003 Dec;4(5):348-53. [https://doi.org/10.3816/cbc.2003.n.040 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/14715110/ PubMed] | ||
+ | # '''RESPECT:''' Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. [https://doi.org/10.1200/jco.20.00184 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/32936713/ PubMed] [https://clinicaltrials.gov/study/NCT01104935 NCT01104935] | ||
− | ===Regimen # | + | ==AC-TH (Paclitaxel) {{#subobject:b52fj1|Regimen=1}}== |
− | {| | + | AC-TH: '''<u>A</u>'''driamycin (Doxorubicin) and '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axol (Paclitaxel) & '''<u>H</u>'''erceptin (Trastuzumab) |
− | | | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | |[[Levels_of_Evidence#Evidence| | + | ===Regimen variant #1, weekly paclitaxel, q3wk trastuzumab {{#subobject:b6d18g|Variant=1}}=== |
− | | | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|Study |
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | |2011-2013 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#AC-THP_.28Paclitaxel.29|AC-THP (Paclitaxel)]]<br>1b. [[#AC-THP_.28Docetaxel.29_2|AC-THP (Docetaxel)]]<br>1c. [[#ddAC-THP_.28Paclitaxel.29_2|ddAC-THP (Paclitaxel)]]<br>1c. [[#ddAC-THP_.28Docetaxel.29|ddAC-THP (Docetaxel)]]<br>1e. [[#EC-THP_.28Paclitaxel.29|EC-THP (Paclitaxel)]]<br>1f. [[#EC-THP_.28Docetaxel.29|EC-THP (Docetaxel)]]<br>1g. [[#ddEC-THP_.28Paclitaxel.29|ddEC-THP (Paclitaxel)]]<br>1h. [[#ddEC-THP_.28Docetaxel.29|ddEC-THP (Docetaxel)]]<br>1i. [[#FAC-THP_.28Paclitaxel.29|FAC-THP (Paclitaxel)]]<br>1j. [[#FAC-THP_.28Docetaxel.29|FAC-THP (Docetaxel)]]<br>1k. [[#FEC-THP_.28Paclitaxel.29|FEC-THP (Paclitaxel)]]<br>1l. [[#FEC-THP_.28Docetaxel.29|FEC-THP (Docetaxel)]]<br>1m. [[#TCHP_.28Docetaxel.29_2|TCHP (Docetaxel)]] |
+ | | style="background-color:#d73027" |Inferior IDFS<sup>1</sup> | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, | + | ''Note that ranges for AC are given in the protocol, replicated here.'' |
− | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | + | <div class="toccolours" style="background-color:#cbd5e8"> |
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, AC portion (cycles 1 to 4)==== | ||
+ | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Chemotherapy, TH portion (cycles 5 to 8)==== | |
− | ==== | + | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 |
− | * | + | ====Targeted therapy, TH portion==== |
− | + | *[[Trastuzumab (Herceptin)]] as follows: | |
− | ''' | + | **Cycle 5: 8 mg/kg IV once on day 1 |
− | + | **Cycles 6 to 22: 6 mg/kg IV once on day 1 | |
− | ====Chemotherapy, TH portion==== | + | '''21-day cycle for 22 cycles (AC x 4; TH x 4)''' |
− | *[[ | + | </div></div><br> |
− | **Cycles 1 | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #2, weekly paclitaxel, weekly trastuzumab {{#subobject:bjug1b|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |rowspan=2|[https://doi.org/10.1056/NEJMoa052122 Romond et al. 2005 (NCCTG N9831)] | ||
+ | |rowspan=2|2000-2005 | ||
+ | |rowspan=2 style="background-color:#1a9851"|Phase 3 (E-RT-esc) | ||
+ | |1. [[Breast_cancer,_HER2-positive_-_historical#AC-T|AC-T]]; weekly paclitaxel | ||
+ | |style="background-color:#1a9850"|Superior OS<sup>1</sup> (secondary endpoint)<br>OS120: 84% vs 75.2%<br>(HR 0.63, 95% CI 0.5-0.73) | ||
+ | |- | ||
+ | |2. [[#AC-T-H_999|AC-T-H]] | ||
+ | |style="background-color:#d9ef8b"|Might have superior DFS<sup>2</sup> (primary endpoint) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the 2014 pooled update.''<br> | ||
+ | ''<sup>2</sup>Reported efficacy is based on the 2011 update.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, AC portion (cycles 1 to 4)==== | ||
+ | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Chemotherapy, TH portion (cycles 5 to 8)==== | ||
+ | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | ||
+ | ====Targeted therapy, TH portion==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 5: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15 | ||
+ | **Cycles 6 to 22: 2 mg/kg IV once per day on days 1, 8, 15 | ||
+ | '''21-day cycle for 22 cycles (AC x 4; TH x 4)''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #3, q3wk paclitaxel, weekly trastuzumab {{#subobject:158d3d|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 17%"|Study | ||
+ | !style="width: 15%"|Dates of enrollment | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 17%"|Comparator | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/NEJMoa052122 Romond et al. 2005 (NSABP B-31)] | ||
+ | |2000-2005 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-RT-esc) | ||
+ | |1a. [[Breast_cancer,_HER2-positive_-_historical#AC-T|AC-T]]; weekly paclitaxel<br>1b. [[Breast_cancer,_HER2-positive_-_historical#AC-T|AC-T]]; q3wk paclitaxel | ||
+ | |style="background-color:#1a9850"|Superior OS<sup>1</sup> (secondary endpoint)<br>OS120: 84% vs 75.2%<br>(HR 0.63, 95% CI 0.5-0.73)<br><br>Superior DFS (primary endpoint) | ||
+ | |style="background-color:#d9ef8b"|Might have superior DASI score | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the 2014 pooled update.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, AC portion (cycles 1 to 4)==== | ||
+ | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Chemotherapy, TH portion (cycles 5 to 8)==== | ||
+ | *[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1 | ||
+ | ====Targeted therapy, TH portion==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15 |
− | ** | + | **Cycles 6 to 22: 2 mg/kg IV once per day on days 1, 8, 15 |
− | + | '''21-day cycle for 22 cycles (AC x 4; TH x 4)''' | |
− | '''21-day cycle for | + | </div></div> |
===References=== | ===References=== | ||
− | # von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [ | + | <!-- no pre-pub disclosed --> |
− | + | # '''NSABP B-31:''' Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1673-84. [https://doi.org/10.1056/NEJMoa052122 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16236738/ PubMed] [https://clinicaltrials.gov/study/NCT00004067 NCT00004067] | |
− | ==ddAC -> | + | ## '''Pooled update:''' Perez EA, Romond EH, Suman VJ, Jeong JH, Davidson NE, Geyer CE Jr, Martino S, Mamounas EP, Kaufman PA, Wolmark N. Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31. J Clin Oncol. 2011 Sep 1;29(25):3366-73. Epub 2011 Jul 18. [https://doi.org/10.1200/JCO.2011.35.0868 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164242/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21768458/ PubMed] |
− | {| class="wikitable" style=" | + | ## '''Pooled update:''' Perez EA, Romond EH, Suman VJ, Jeong JH, Sledge G, Geyer CE Jr, Martino S, Rastogi P, Gralow J, Swain SM, Winer EP, Colon-Otero G, Davidson NE, Mamounas E, Zujewski JA, Wolmark N. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 2014 Nov 20;32(33):3744-52. Epub 2014 Oct 20. [https://doi.org/10.1200/JCO.2014.55.5730 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226805/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25332249/ PubMed] |
+ | ## '''HRQoL analysis:''' Ganz PA, Romond EH, Cecchini RS, Rastogi P, Geyer CE Jr, Swain SM, Jeong JH, Fehrenbacher L, Gross HM, Brufsky AM, Flynn PJ, Wahl TA, Seay TE, Wade JL 3rd, Biggs DD, Atkins JN, Polikoff J, Zapas JL, Mamounas EP, Wolmark N. Long-term follow-up of cardiac function and quality of life for patients in NSABP protocol B-31/NRG Oncology: a randomized trial comparing the safety and efficacy of doxorubicin and cyclophosphamide (AC) followed by paclitaxel with AC followed by paclitaxel and trastuzumab in patients with node-positive breast cancer with tumors overexpressing human epidermal growth factor receptor 2. J Clin Oncol. 2017 Dec 10;35(35):3942-3948. Epub 2017 Oct 26. [https://doi.org/10.1200/JCO.2017.74.1165 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5721228/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29072977/ PubMed] | ||
+ | <!-- no pre-pub disclosed --> | ||
+ | # '''NCCTG N9831:''' Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1673-84. [https://doi.org/10.1056/NEJMoa052122 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16236738/ PubMed] [https://clinicaltrials.gov/study/NCT00005970 NCT00005970] | ||
+ | ## '''Pooled update:''' Perez EA, Romond EH, Suman VJ, Jeong JH, Davidson NE, Geyer CE Jr, Martino S, Mamounas EP, Kaufman PA, Wolmark N. Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31. J Clin Oncol. 2011 Sep 1;29(25):3366-73. Epub 2011 Jul 18. [https://doi.org/10.1200/JCO.2011.35.0868 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164242/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21768458/ PubMed] | ||
+ | ## '''Update:''' Perez EA, Suman VJ, Davidson NE, Gralow JR, Kaufman PA, Visscher DW, Chen B, Ingle JN, Dakhil SR, Zujewski J, Moreno-Aspitia A, Pisansky TM, Jenkins RB. Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer. J Clin Oncol. 2011 Dec 1;29(34):4491-7. Epub 2011 Oct 31. [https://doi.org/10.1200/JCO.2011.36.7045 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236650/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22042958/ PubMed] | ||
+ | ## '''Pooled update:''' Perez EA, Romond EH, Suman VJ, Jeong JH, Sledge G, Geyer CE Jr, Martino S, Rastogi P, Gralow J, Swain SM, Winer EP, Colon-Otero G, Davidson NE, Mamounas E, Zujewski JA, Wolmark N. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 2014 Nov 20;32(33):3744-52. Epub 2014 Oct 20. [https://doi.org/10.1200/JCO.2014.55.5730 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226805/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25332249/ PubMed] | ||
+ | # '''APHINITY:''' von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [https://doi.org/10.1056/NEJMoa1703643 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28581356/ PubMed] [https://clinicaltrials.gov/study/NCT01358877 NCT01358877] | ||
+ | ##'''Update:''' Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. [https://doi.org/10.1200/jco.20.01204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33539215/ PubMed] | ||
+ | ==ddAC-ddTH (Paclitaxel) {{#subobject:b52056|Regimen=1}}== | ||
+ | ddAC-ddTH: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>A</u>'''driamycin (Doxorubicin) and '''<u>C</u>'''yclophosphamide, followed by '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>T</u>'''axol (Paclitaxel) & '''<u>H</u>'''erceptin (Trastuzumab) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:cdafd0|Variant=1}}=== | ||
+ | {| class="wikitable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2007.12.0733 Dang et al. 2008] | ||
+ | |2005 | ||
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
− | + | ====Preceding treatment==== | |
− | ===Regimen {{#subobject: | + | *[[Surgery#Breast_cancer_surgery|Surgery]] |
− | {| | + | </div> |
− | | | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | |[[Levels_of_Evidence#Evidence| | + | ====Chemotherapy, ddAC portion (cycles 1 to 4)==== |
− | | | + | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 |
− | |[[Levels_of_Evidence# | + | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 |
+ | ====Chemotherapy, ddTH portion (cycles 5 to 8)==== | ||
+ | *[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1 | ||
+ | ====Targeted therapy, ddTH portion==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 5: 4 mg/kg IV once on day 1, then 2 mg/kg IV once on day 8 | ||
+ | **Cycles 6 to 8: 2 mg/kg IV once per day on days 1 & 8 | ||
+ | **Cycles 9 to 53: 2 mg/kg IV once on day 1 | ||
+ | ====Supportive therapy, both portions (cycles 1 to 8)==== | ||
+ | *[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2, given 24 hours after chemotherapy | ||
+ | '''14-day cycle for 8 cycles (ddAC x 4; ddTH x 4)''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[#Trastuzumab_monotherapy_2|Trastuzumab]] maintenance x 44 weeks (1 year total) | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # Dang C, Fornier M, Sugarman S, Troso-Sandoval T, Lake D, D'Andrea G, Seidman A, Sklarin N, Dickler M, Currie V, Gilewski T, Moynahan ME, Drullinsky P, Robson M, Wasserheit-Leiblich C, Mills N, Steingart R, Panageas K, Norton L, Hudis C. The safety of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel with trastuzumab in HER-2/neu overexpressed/amplified breast cancer. J Clin Oncol. 2008 Mar 10;26(8):1216-22. [https://doi.org/10.1200/jco.2007.12.0733 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18323546/ PubMed] | ||
+ | ==AC-TH (Docetaxel) {{#subobject:77hgad|Regimen=1}}== | ||
+ | AC-TH: '''<u>A</u>'''driamycin (Doxorubicin) and '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axotere (Docetaxel) & '''<u>H</u>'''erceptin (Trastuzumab) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1 {{#subobject:b6du11|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | |2011-2013 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#AC-THP_.28Paclitaxel.29|AC-THP (Paclitaxel)]]<br>1b. [[#AC-THP_.28Docetaxel.29_2|AC-THP (Docetaxel)]]<br>1c. [[#ddAC-THP_.28Paclitaxel.29_2|ddAC-THP (Paclitaxel)]]<br>1c. [[#ddAC-THP_.28Docetaxel.29|ddAC-THP (Docetaxel)]]<br>1e. [[#EC-THP_.28Paclitaxel.29|EC-THP (Paclitaxel)]]<br>1f. [[#EC-THP_.28Docetaxel.29|EC-THP (Docetaxel)]]<br>1g. [[#ddEC-THP_.28Paclitaxel.29|ddEC-THP (Paclitaxel)]]<br>1h. [[#ddEC-THP_.28Docetaxel.29|ddEC-THP (Docetaxel)]]<br>1i. [[#FAC-THP_.28Paclitaxel.29|FAC-THP (Paclitaxel)]]<br>1j. [[#FAC-THP_.28Docetaxel.29|FAC-THP (Docetaxel)]]<br>1k. [[#FEC-THP_.28Paclitaxel.29|FEC-THP (Paclitaxel)]]<br>1l. [[#FEC-THP_.28Docetaxel.29|FEC-THP (Docetaxel)]]<br>1m. [[#TCHP_.28Docetaxel.29_2|TCHP (Docetaxel)]] |
+ | | style="background-color:#d73027" |Inferior IDFS<sup>1</sup> | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, | + | ''Note that ranges for AC are given in the protocol, replicated here.'' |
− | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | + | <div class="toccolours" style="background-color:#cbd5e8"> |
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, AC portion (cycles 1 to 4)==== | ||
+ | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Chemotherapy, TH portion (cycles 5 to 8)==== | |
− | + | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 | |
− | + | ====Targeted therapy, TH portion==== | |
− | |||
− | |||
− | |||
− | ====Chemotherapy, | ||
− | *[[ | ||
− | |||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 6 to 22: 6 mg/kg IV once on day 1 |
− | + | '''21-day cycle for 22 cycles (AC x 4; TH x 4)''' | |
− | + | </div></div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #2 {{#subobject:nb8111|Variant=1}}=== | |
− | '''21-day cycle for | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | + | !style="width: 20%"|Study | |
− | + | !style="width: 20%"|Dates of enrollment | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
− | + | !style="width: 20%"|Comparator | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | ===Regimen # | ||
− | {| | ||
− | | | ||
− | |[[Levels_of_Evidence#Evidence| | ||
− | | | ||
− | |[[Levels_of_Evidence# | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | |2011-2013 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#AC-THP_.28Paclitaxel.29|AC-THP (Paclitaxel)]]<br>1b. [[#AC-THP_.28Docetaxel.29_2|AC-THP (Docetaxel)]]<br>1c. [[#ddAC-THP_.28Paclitaxel.29_2|ddAC-THP (Paclitaxel)]]<br>1c. [[#ddAC-THP_.28Docetaxel.29|ddAC-THP (Docetaxel)]]<br>1e. [[#EC-THP_.28Paclitaxel.29|EC-THP (Paclitaxel)]]<br>1f. [[#EC-THP_.28Docetaxel.29|EC-THP (Docetaxel)]]<br>1g. [[#ddEC-THP_.28Paclitaxel.29|ddEC-THP (Paclitaxel)]]<br>1h. [[#ddEC-THP_.28Docetaxel.29|ddEC-THP (Docetaxel)]]<br>1i. [[#FAC-THP_.28Paclitaxel.29|FAC-THP (Paclitaxel)]]<br>1j. [[#FAC-THP_.28Docetaxel.29|FAC-THP (Docetaxel)]]<br>1k. [[#FEC-THP_.28Paclitaxel.29|FEC-THP (Paclitaxel)]]<br>1l. [[#FEC-THP_.28Docetaxel.29|FEC-THP (Docetaxel)]]<br>1m. [[#TCHP_.28Docetaxel.29_2|TCHP (Docetaxel)]] |
+ | | style="background-color:#d73027" |Inferior IDFS<sup>1</sup> | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, | + | ''Note that ranges for AC are given in the protocol, replicated here.'' |
− | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | + | <div class="toccolours" style="background-color:#cbd5e8"> |
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, AC portion (cycles 1 to 4)==== | ||
+ | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Chemotherapy, TH portion (cycles 5 to 7)==== | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | ====Chemotherapy, | ||
*[[Docetaxel (Taxotere)]] as follows: | *[[Docetaxel (Taxotere)]] as follows: | ||
− | **Cycles | + | **Cycle 5: 75 mg/m<sup>2</sup> IV once on day 1 |
+ | **Cycles 6 & 7: 100 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, TH portion==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 6 to 22: 6 mg/kg IV once on day 1 |
− | + | '''21-day cycle for 22 cycles (AC x 4; TH x 3)''' | |
− | + | </div></div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #3 {{#subobject:nb8zb1|Variant=1}}=== | |
− | '''21-day cycle for | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | + | !style="width: 20%"|Study | |
− | ===Regimen # | + | !style="width: 20%"|Dates of enrollment |
− | {| | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | | | + | !style="width: 20%"|Comparator |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | | | ||
− | |[[Levels_of_Evidence# | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | |2011-2013 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#AC-THP_.28Paclitaxel.29|AC-THP (Paclitaxel)]]<br>1b. [[#AC-THP_.28Docetaxel.29_2|AC-THP (Docetaxel)]]<br>1c. [[#ddAC-THP_.28Paclitaxel.29_2|ddAC-THP (Paclitaxel)]]<br>1c. [[#ddAC-THP_.28Docetaxel.29|ddAC-THP (Docetaxel)]]<br>1e. [[#EC-THP_.28Paclitaxel.29|EC-THP (Paclitaxel)]]<br>1f. [[#EC-THP_.28Docetaxel.29|EC-THP (Docetaxel)]]<br>1g. [[#ddEC-THP_.28Paclitaxel.29|ddEC-THP (Paclitaxel)]]<br>1h. [[#ddEC-THP_.28Docetaxel.29|ddEC-THP (Docetaxel)]]<br>1i. [[#FAC-THP_.28Paclitaxel.29|FAC-THP (Paclitaxel)]]<br>1j. [[#FAC-THP_.28Docetaxel.29|FAC-THP (Docetaxel)]]<br>1k. [[#FEC-THP_.28Paclitaxel.29|FEC-THP (Paclitaxel)]]<br>1l. [[#FEC-THP_.28Docetaxel.29|FEC-THP (Docetaxel)]]<br>1m. [[#TCHP_.28Docetaxel.29_2|TCHP (Docetaxel)]] |
+ | | style="background-color:#d73027" |Inferior IDFS<sup>1</sup> | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, | + | ''Note that ranges for AC are given in the protocol, replicated here.'' |
− | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | + | <div class="toccolours" style="background-color:#cbd5e8"> |
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, AC portion (cycles 1 to 4)==== | ||
+ | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Chemotherapy, TH portion (cycles 5 to 7)==== | |
− | ==== | + | *[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1 |
− | * | + | ====Targeted therapy, TH portion==== |
− | + | *[[Trastuzumab (Herceptin)]] as follows: | |
− | ''' | + | **Cycle 5: 8 mg/kg IV once on day 1 |
− | + | **Cycles 6 to 22: 6 mg/kg IV once on day 1 | |
− | ====Chemotherapy, | + | '''21-day cycle for 22 cycles (AC x 4; TH x 3)''' |
− | *[[ | + | </div></div><br> |
− | * | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | * | + | ===Regimen variant #4 {{#subobject:hga7813|Variant=1}}=== |
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3268553/ Slamon et al. 2011 (BCIRG 006)] | ||
+ | |rowspan=2|2001-2004 | ||
+ | |rowspan=2 style="background-color:#1a9851" |Phase 3 (E-RT-esc) | ||
+ | |1. [[Breast_cancer,_HER2-positive_-_historical#AC-D|AC-D]] | ||
+ | | style="background-color:#1a9850" |Superior OS (secondary endpoint) | ||
+ | |- | ||
+ | |2. [[#TCH_.28Docetaxel.29|TCH]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, AC portion (cycles 1 to 4)==== | ||
+ | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Chemotherapy, TH portion (cycles 5 to 8)==== | ||
+ | *[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, TH portion==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15 |
− | + | **Cycles 6 to 8: 2 mg/kg IV once per day on days 1, 8, 15 | |
− | * | + | **Cycles 9 to 21: 6 mg/kg IV once on day 1 |
− | * | + | '''21-day cycle for 21 cycles (AC x 4; TH x 4)''' |
− | ** | + | </div></div> |
− | + | ===References=== | |
− | '''21-day cycle for | + | <!-- no pre-pub disclosed --> |
− | + | # '''BCIRG 006:''' Slamon D, Eiermann W, Robert N, Pienkowski T, Martín M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J; Breast Cancer International Research Group. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011 Oct 6;365(14):1273-83. [https://doi.org/10.1056/NEJMoa0910383 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3268553/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21991949/ PubMed] [https://clinicaltrials.gov/study/NCT00021255 NCT00021255] | |
− | ===Regimen | + | # '''APHINITY:''' von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [https://doi.org/10.1056/NEJMoa1703643 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28581356/ PubMed] [https://clinicaltrials.gov/study/NCT01358877 NCT01358877] |
− | {| | + | ##'''Update:''' Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. [https://doi.org/10.1200/jco.20.01204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33539215/ PubMed] |
− | | | + | ==AC-THP (Paclitaxel) {{#subobject:c52fj1|Regimen=1}}== |
− | |[[Levels_of_Evidence#Evidence| | + | AC-THP: '''<u>A</u>'''driamycin (Doxorubicin) and '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axol (Paclitaxel), '''<u>H</u>'''erceptin (Trastuzumab), '''<u>P</u>'''ertuzumab |
− | | | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | |[[Levels_of_Evidence# | + | ===Regimen {{#subobject:c6d18g|Variant=1}}=== |
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" |
− | |[[# | + | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-133-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' |
− | |style="background-color:# | + | |- |
+ | |} --> | ||
+ | |2011-2013 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |1a. [[#AC-TH_.28Paclitaxel.29_2|AC-TH (Paclitaxel)]]<br>1b. [[#AC-TH_.28Docetaxel.29|AC-TH (Docetaxel)]]<br>1c. [[#ddAC-TH_.28Paclitaxel.29|ddAC-TH (Paclitaxel)]]<br>1d. [[#ddAC-TH_.28Docetaxel.29|ddAC-TH (Docetaxel)]]<br>1e. [[#EC-TH_.28Paclitaxel.29|EC-TH (Paclitaxel)]]<br>1f. [[#EC-TH_.28Docetaxel.29_2|EC-TH (Docetaxel)]]<br>1g. [[#ddEC-TH_.28Paclitaxel.29|ddEC-TH (Paclitaxel)]]<br>1h. [[#ddEC-TH_.28Docetaxel.29|ddEC-TH (Docetaxel)]]<br>1i. [[#FAC-TH_.28Paclitaxel.29|FAC-TH (Paclitaxel)]]<br>1j. [[#FAC-TH_.28Docetaxel.29|FAC-TH (Docetaxel)]]<br>1k. [[#FEC-TH_.28Paclitaxel.29_2|FEC-TH (Paclitaxel)]]<br>1l. [[#FEC-TH_.28Docetaxel.29|FEC-TH (Docetaxel)]]<br>1m. [[#TCH_.28Docetaxel.29|TCH (Taxotere)]] | ||
+ | | style="background-color:#1a9850" |Superior IDFS<sup>1</sup> (primary endpoint)<br>IDFS72: 91% vs 88%<br>(HR 0.76, 95% CI 0.64-0.91) | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ Krop et al. 2021 (KAITLIN)] | ||
+ | |2014-01 to 2015-06 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#AC-KP_999|AC-KP]]<br>1b. [[#ddAC-KP_999|ddAC-KP]]<br>1c. [[#EC-KP_999|EC-KP]]<br>1d. [[#ddEC-KP|ddEC-KP]]<br>1e. [[#FEC-KP|FEC-KP]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of IDFS | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, | + | ''Note that ranges for AC are given in the protocol, replicated here.'' |
− | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | + | <div class="toccolours" style="background-color:#cbd5e8"> |
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, AC portion (cycles 1 to 4)==== | ||
+ | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Chemotherapy, THP portion (cycles 5 to 8)==== | |
− | + | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | |
− | + | ====Targeted therapy, THP portion (cycles 5 to 22)==== | |
− | + | *[[Trastuzumab (Herceptin)]] as follows: | |
− | + | **Cycle 5: 8 mg/kg IV once on day 1 | |
− | + | **Cycles 6 to 22: 6 mg/kg IV once on day 1 | |
− | ====Chemotherapy, THP portion==== | + | *[[Pertuzumab (Perjeta)]] as follows: |
− | *[[ | + | **Cycle 5: 840 mg IV once on day 1 |
− | + | **Cycles 6 to 22: 420 mg IV once on day 1 | |
− | *[[Trastuzumab (Herceptin)]] as follows: | + | '''21-day cycle for 22 cycles (AC x 4; THP x 4)''' |
− | **Cycle | + | </div></div> |
− | ** | ||
− | *[[Pertuzumab (Perjeta)]] as follows: | ||
− | **Cycle | ||
− | ** | ||
− | |||
− | '''21-day cycle for | ||
− | |||
===References=== | ===References=== | ||
− | # von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [ | + | # '''APHINITY:''' von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [https://doi.org/10.1056/NEJMoa1703643 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28581356/ PubMed] [https://clinicaltrials.gov/study/NCT01358877 NCT01358877] |
− | + | ##'''Update:''' Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. [https://doi.org/10.1200/jco.20.01204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33539215/ PubMed] | |
− | == | + | #'''KAITLIN:''' Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. [https://doi.org/10.1200/jco.21.00896 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34890214/ PubMed] [https://clinicaltrials.gov/study/NCT01966471 NCT01966471] |
− | {| class="wikitable" style=" | + | ==AC-THP (Docetaxel) {{#subobject:87hgad|Regimen=1}}== |
+ | AC-THP: '''<u>A</u>'''driamycin (Doxorubicin) and '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axotere (Docetaxel), '''<u>H</u>'''erceptin (Trastuzumab), '''<u>P</u>'''ertuzumab | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1 {{#subobject:b6eu11|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-133-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2011-2013 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |1a. [[#AC-TH_.28Paclitaxel.29_2|AC-TH (Paclitaxel)]]<br>1b. [[#AC-TH_.28Docetaxel.29|AC-TH (Docetaxel)]]<br>1c. [[#ddAC-TH_.28Paclitaxel.29|ddAC-TH (Paclitaxel)]]<br>1d. [[#ddAC-TH_.28Docetaxel.29|ddAC-TH (Docetaxel)]]<br>1e. [[#EC-TH_.28Paclitaxel.29|EC-TH (Paclitaxel)]]<br>1f. [[#EC-TH_.28Docetaxel.29_2|EC-TH (Docetaxel)]]<br>1g. [[#ddEC-TH_.28Paclitaxel.29|ddEC-TH (Paclitaxel)]]<br>1h. [[#ddEC-TH_.28Docetaxel.29|ddEC-TH (Docetaxel)]]<br>1i. [[#FAC-TH_.28Paclitaxel.29|FAC-TH (Paclitaxel)]]<br>1j. [[#FAC-TH_.28Docetaxel.29|FAC-TH (Docetaxel)]]<br>1k. [[#FEC-TH_.28Paclitaxel.29_2|FEC-TH (Paclitaxel)]]<br>1l. [[#FEC-TH_.28Docetaxel.29|FEC-TH (Docetaxel)]]<br>1m. [[#TCH_.28Docetaxel.29|TCH (Taxotere)]] | ||
+ | | style="background-color:#1a9850" |Superior IDFS<sup>1</sup> (primary endpoint)<br>IDFS72: 91% vs 88%<br>(HR 0.76, 95% CI 0.64-0.91) | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ Krop et al. 2021 (KAITLIN)] | ||
+ | |2014-01 to 2015-06 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#AC-KP_999|AC-KP]]<br>1b. [[#ddAC-KP_999|ddAC-KP]]<br>1c. [[#EC-KP_999|EC-KP]]<br>1d. [[#ddEC-KP|ddEC-KP]]<br>1e. [[#FEC-KP|FEC-KP]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of IDFS | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> | |
− | ===Regimen {{#subobject: | + | ''Note that ranges for AC are given in the protocol, replicated here.'' |
− | {| | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | | | + | ====Preceding treatment==== |
− | |[[Levels_of_Evidence#Evidence| | + | *[[Surgery#Breast_cancer_surgery|Surgery]] |
− | | | + | </div> |
− | |[[Levels_of_Evidence# | + | <div class="toccolours" style="background-color:#b3e2cd"> |
+ | ====Chemotherapy, AC portion (cycles 1 to 4)==== | ||
+ | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Chemotherapy, THP portion (cycles 5 to 8)==== | ||
+ | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, THP portion (cycles 5 to 22)==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 5: 8 mg/kg IV once on day 1 | ||
+ | **Cycles 6 to 22: 6 mg/kg IV once on day 1 | ||
+ | *[[Pertuzumab (Perjeta)]] as follows: | ||
+ | **Cycle 5: 840 mg IV once on day 1 | ||
+ | **Cycles 6 to 22: 420 mg IV once on day 1 | ||
+ | '''21-day cycle for 22 cycles (AC x 4; THP x 4)''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2 {{#subobject:nb8211|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" |
− | |[[# | + | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-133-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' |
− | |style="background-color:# | + | |- |
+ | |} --> | ||
+ | |2011-2013 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |1a. [[#AC-TH_.28Paclitaxel.29_2|AC-TH (Paclitaxel)]]<br>1b. [[#AC-TH_.28Docetaxel.29|AC-TH (Docetaxel)]]<br>1c. [[#ddAC-TH_.28Paclitaxel.29|ddAC-TH (Paclitaxel)]]<br>1d. [[#ddAC-TH_.28Docetaxel.29|ddAC-TH (Docetaxel)]]<br>1e. [[#EC-TH_.28Paclitaxel.29|EC-TH (Paclitaxel)]]<br>1f. [[#EC-TH_.28Docetaxel.29_2|EC-TH (Docetaxel)]]<br>1g. [[#ddEC-TH_.28Paclitaxel.29|ddEC-TH (Paclitaxel)]]<br>1h. [[#ddEC-TH_.28Docetaxel.29|ddEC-TH (Docetaxel)]]<br>1i. [[#FAC-TH_.28Paclitaxel.29|FAC-TH (Paclitaxel)]]<br>1j. [[#FAC-TH_.28Docetaxel.29|FAC-TH (Docetaxel)]]<br>1k. [[#FEC-TH_.28Paclitaxel.29_2|FEC-TH (Paclitaxel)]]<br>1l. [[#FEC-TH_.28Docetaxel.29|FEC-TH (Docetaxel)]]<br>1m. [[#TCH_.28Docetaxel.29|TCH (Taxotere)]] | ||
+ | | style="background-color:#1a9850" |Superior IDFS<sup>1</sup> (primary endpoint)<br>IDFS72: 91% vs 88%<br>(HR 0.76, 95% CI 0.64-0.91) | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ Krop et al. 2021 (KAITLIN)] | ||
+ | |2014-01 to 2015-06 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#AC-KP_999|AC-KP]]<br>1b. [[#ddAC-KP_999|ddAC-KP]]<br>1c. [[#EC-KP_999|EC-KP]]<br>1d. [[#ddEC-KP|ddEC-KP]]<br>1e. [[#FEC-KP|FEC-KP]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of IDFS | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, | + | ''Note that ranges for AC are given in the protocol, replicated here.'' |
− | *[[ | + | <div class="toccolours" style="background-color:#cbd5e8"> |
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, AC portion (cycles 1 to 4)==== | ||
+ | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Chemotherapy, THP portion (cycles 5 to 7)==== | |
− | + | *[[Docetaxel (Taxotere)]] as follows: | |
− | + | **Cycle 5: 75 mg/m<sup>2</sup> IV once on day 1 | |
− | + | **Cycles 6 & 7: 100 mg/m<sup>2</sup> IV once on day 1 | |
− | + | ====Targeted therapy, THP portion (cycles 5 to 22)==== | |
− | |||
− | ====Chemotherapy, | ||
− | *[[ | ||
− | ** | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 6 to 22: 6 mg/kg IV once on day 1 |
− | + | *[[Pertuzumab (Perjeta)]] as follows: | |
− | '''21-day cycle for | + | **Cycle 5: 840 mg IV once on day 1 |
− | + | **Cycles 6 to 22: 420 mg IV once on day 1 | |
− | === | + | '''21-day cycle for 22 cycles (AC x 4; THP x 3)''' |
− | + | </div></div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #3 {{#subobject:nb9zb1|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-133-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2011-2013 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |1a. [[#AC-TH_.28Paclitaxel.29_2|AC-TH (Paclitaxel)]]<br>1b. [[#AC-TH_.28Docetaxel.29|AC-TH (Docetaxel)]]<br>1c. [[#ddAC-TH_.28Paclitaxel.29|ddAC-TH (Paclitaxel)]]<br>1d. [[#ddAC-TH_.28Docetaxel.29|ddAC-TH (Docetaxel)]]<br>1e. [[#EC-TH_.28Paclitaxel.29|EC-TH (Paclitaxel)]]<br>1f. [[#EC-TH_.28Docetaxel.29_2|EC-TH (Docetaxel)]]<br>1g. [[#ddEC-TH_.28Paclitaxel.29|ddEC-TH (Paclitaxel)]]<br>1h. [[#ddEC-TH_.28Docetaxel.29|ddEC-TH (Docetaxel)]]<br>1i. [[#FAC-TH_.28Paclitaxel.29|FAC-TH (Paclitaxel)]]<br>1j. [[#FAC-TH_.28Docetaxel.29|FAC-TH (Docetaxel)]]<br>1k. [[#FEC-TH_.28Paclitaxel.29_2|FEC-TH (Paclitaxel)]]<br>1l. [[#FEC-TH_.28Docetaxel.29|FEC-TH (Docetaxel)]]<br>1m. [[#TCH_.28Docetaxel.29|TCH (Taxotere)]] | ||
+ | | style="background-color:#1a9850" |Superior IDFS<sup>1</sup> (primary endpoint)<br>IDFS72: 91% vs 88%<br>(HR 0.76, 95% CI 0.64-0.91) | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ Krop et al. 2021 (KAITLIN)] | ||
+ | |2014-01 to 2015-06 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#AC-KP_999|AC-KP]]<br>1b. [[#ddAC-KP_999|ddAC-KP]]<br>1c. [[#EC-KP_999|EC-KP]]<br>1d. [[#ddEC-KP|ddEC-KP]]<br>1e. [[#FEC-KP|FEC-KP]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of IDFS | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> | |
− | ===Regimen | + | ''Note that ranges for AC are given in the protocol, replicated here.'' |
− | {| | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | | | + | ====Preceding treatment==== |
− | |[[Levels_of_Evidence#Evidence| | + | *[[Surgery#Breast_cancer_surgery|Surgery]] |
− | | | + | </div> |
− | |[[Levels_of_Evidence# | + | <div class="toccolours" style="background-color:#b3e2cd"> |
+ | ====Chemotherapy, AC portion (cycles 1 to 4)==== | ||
+ | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Chemotherapy, THP portion (cycles 5 to 7)==== | ||
+ | *[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, THP portion (cycles 5 to 22)==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 5: 8 mg/kg IV once on day 1 | ||
+ | **Cycles 6 to 22: 6 mg/kg IV once on day 1 | ||
+ | *[[Pertuzumab (Perjeta)]] as follows: | ||
+ | **Cycle 5: 840 mg IV once on day 1 | ||
+ | **Cycles 6 to 22: 420 mg IV once on day 1 | ||
+ | '''21-day cycle for 22 cycles (AC x 4; THP x 3)''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''APHINITY:''' von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [https://doi.org/10.1056/NEJMoa1703643 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28581356/ PubMed] [https://clinicaltrials.gov/study/NCT01358877 NCT01358877] | ||
+ | ##'''Update:''' Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. [https://doi.org/10.1200/jco.20.01204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33539215/ PubMed] | ||
+ | #'''KAITLIN:''' Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. [https://doi.org/10.1200/jco.21.00896 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34890214/ PubMed] [https://clinicaltrials.gov/study/NCT01966471 NCT01966471] | ||
+ | ==ddAC-TH (Paclitaxel) {{#subobject:b52056|Regimen=1}}== | ||
+ | ddAC-TH: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>A</u>'''driamycin (Doxorubicin) and '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axol (Paclitaxel) & '''<u>H</u>'''erceptin (Trastuzumab) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:b6d1ca|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | |2011-2013 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#AC-THP_.28Paclitaxel.29|AC-THP (Paclitaxel)]]<br>1b. [[#AC-THP_.28Docetaxel.29_2|AC-THP (Docetaxel)]]<br>1c. [[#ddAC-THP_.28Paclitaxel.29_2|ddAC-THP (Paclitaxel)]]<br>1c. [[#ddAC-THP_.28Docetaxel.29|ddAC-THP (Docetaxel)]]<br>1e. [[#EC-THP_.28Paclitaxel.29|EC-THP (Paclitaxel)]]<br>1f. [[#EC-THP_.28Docetaxel.29|EC-THP (Docetaxel)]]<br>1g. [[#ddEC-THP_.28Paclitaxel.29|ddEC-THP (Paclitaxel)]]<br>1h. [[#ddEC-THP_.28Docetaxel.29|ddEC-THP (Docetaxel)]]<br>1i. [[#FAC-THP_.28Paclitaxel.29|FAC-THP (Paclitaxel)]]<br>1j. [[#FAC-THP_.28Docetaxel.29|FAC-THP (Docetaxel)]]<br>1k. [[#FEC-THP_.28Paclitaxel.29|FEC-THP (Paclitaxel)]]<br>1l. [[#FEC-THP_.28Docetaxel.29|FEC-THP (Docetaxel)]]<br>1m. [[#TCHP_.28Docetaxel.29_2|TCHP (Docetaxel)]] |
+ | | style="background-color:#d73027" |Inferior IDFS<sup>1</sup> | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, | + | ''Note that ranges for ddAC are given in the protocol, replicated here.'' |
− | *[[ | + | <div class="toccolours" style="background-color:#cbd5e8"> |
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, ddAC portion (cycles 1 to 4)==== | ||
+ | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Supportive therapy, ddAC portion (cycles 1 to 4)==== | |
− | ====Supportive | + | *[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] support (drug/dose/schedule not specified) |
− | *G-CSF support (drug/dose/schedule not specified) | + | ====Chemotherapy, TH portion (cycles 5 to 8)==== |
− | + | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | |
− | + | ====Targeted therapy, TH portion==== | |
− | |||
− | ====Chemotherapy, TH portion==== | ||
− | *[[ | ||
− | |||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 6 to 22: 6 mg/kg IV once on day 1 |
− | + | '''14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)''' | |
− | '''21-day cycle for | + | </div></div> |
− | + | ===References=== | |
− | ===Regimen # | + | # '''APHINITY:''' von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [https://doi.org/10.1056/NEJMoa1703643 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28581356/ PubMed] [https://clinicaltrials.gov/study/NCT01358877 NCT01358877] |
− | {| | + | ##'''Update:''' Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. [https://doi.org/10.1200/jco.20.01204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33539215/ PubMed] |
− | | | + | ==ddAC-TH (Docetaxel) {{#subobject:b52cf6|Regimen=1}}== |
− | |[[Levels_of_Evidence#Evidence| | + | ddAC-TH: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>A</u>'''driamycin (Doxorubicin) and '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axotere (Docetaxel) & '''<u>H</u>'''erceptin (Trastuzumab) |
− | | | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | |[[Levels_of_Evidence# | + | ===Regimen variant #1 {{#subobject:b6d7yy|Variant=1}}=== |
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | |2011-2013 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#AC-THP_.28Paclitaxel.29|AC-THP (Paclitaxel)]]<br>1b. [[#AC-THP_.28Docetaxel.29_2|AC-THP (Docetaxel)]]<br>1c. [[#ddAC-THP_.28Paclitaxel.29_2|ddAC-THP (Paclitaxel)]]<br>1c. [[#ddAC-THP_.28Docetaxel.29|ddAC-THP (Docetaxel)]]<br>1e. [[#EC-THP_.28Paclitaxel.29|EC-THP (Paclitaxel)]]<br>1f. [[#EC-THP_.28Docetaxel.29|EC-THP (Docetaxel)]]<br>1g. [[#ddEC-THP_.28Paclitaxel.29|ddEC-THP (Paclitaxel)]]<br>1h. [[#ddEC-THP_.28Docetaxel.29|ddEC-THP (Docetaxel)]]<br>1i. [[#FAC-THP_.28Paclitaxel.29|FAC-THP (Paclitaxel)]]<br>1j. [[#FAC-THP_.28Docetaxel.29|FAC-THP (Docetaxel)]]<br>1k. [[#FEC-THP_.28Paclitaxel.29|FEC-THP (Paclitaxel)]]<br>1l. [[#FEC-THP_.28Docetaxel.29|FEC-THP (Docetaxel)]]<br>1m. [[#TCHP_.28Docetaxel.29_2|TCHP (Docetaxel)]] |
+ | | style="background-color:#d73027" |Inferior IDFS<sup>1</sup> | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, | + | ''Note that ranges for ddAC are given in the protocol, replicated here.'' |
− | *[[ | + | <div class="toccolours" style="background-color:#cbd5e8"> |
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, ddAC portion (cycles 1 to 4)==== | ||
+ | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Supportive therapy, ddAC portion (cycles 1 to 4)==== | |
− | ====Supportive | + | *[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] support (drug/dose/schedule not specified) |
− | *G-CSF support (drug/dose/schedule not specified) | + | ====Chemotherapy, TH portion (cycles 5 to 8)==== |
− | + | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 | |
− | + | ====Targeted therapy, TH portion==== | |
− | |||
− | ====Chemotherapy, TH portion==== | ||
− | *[[Docetaxel (Taxotere)]] | ||
− | |||
− | |||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 6 to 22: 6 mg/kg IV once on day 1 |
− | + | '''14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)''' | |
− | '''21-day cycle for | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | ===Regimen # | + | ===Regimen variant #2 {{#subobject:hg81yy|Variant=1}}=== |
− | {| | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | | | + | !style="width: 20%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Dates of enrollment |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | |2011-2013 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#AC-THP_.28Paclitaxel.29|AC-THP (Paclitaxel)]]<br>1b. [[#AC-THP_.28Docetaxel.29_2|AC-THP (Docetaxel)]]<br>1c. [[#ddAC-THP_.28Paclitaxel.29_2|ddAC-THP (Paclitaxel)]]<br>1c. [[#ddAC-THP_.28Docetaxel.29|ddAC-THP (Docetaxel)]]<br>1e. [[#EC-THP_.28Paclitaxel.29|EC-THP (Paclitaxel)]]<br>1f. [[#EC-THP_.28Docetaxel.29|EC-THP (Docetaxel)]]<br>1g. [[#ddEC-THP_.28Paclitaxel.29|ddEC-THP (Paclitaxel)]]<br>1h. [[#ddEC-THP_.28Docetaxel.29|ddEC-THP (Docetaxel)]]<br>1i. [[#FAC-THP_.28Paclitaxel.29|FAC-THP (Paclitaxel)]]<br>1j. [[#FAC-THP_.28Docetaxel.29|FAC-THP (Docetaxel)]]<br>1k. [[#FEC-THP_.28Paclitaxel.29|FEC-THP (Paclitaxel)]]<br>1l. [[#FEC-THP_.28Docetaxel.29|FEC-THP (Docetaxel)]]<br>1m. [[#TCHP_.28Docetaxel.29_2|TCHP (Docetaxel)]] |
+ | | style="background-color:#d73027" |Inferior IDFS<sup>1</sup> | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, | + | ''Note that ranges for ddAC are given in the protocol, replicated here.'' |
− | *[[ | + | <div class="toccolours" style="background-color:#cbd5e8"> |
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, ddAC portion (cycles 1 to 4)==== | ||
+ | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Supportive therapy, ddAC portion (cycles 1 to 4)==== | |
− | ====Supportive | + | *[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] support (drug/dose/schedule not specified) |
− | *G-CSF support (drug/dose/schedule not specified) | ||
− | |||
− | |||
− | |||
====Chemotherapy, TH portion==== | ====Chemotherapy, TH portion==== | ||
*[[Docetaxel (Taxotere)]] as follows: | *[[Docetaxel (Taxotere)]] as follows: | ||
− | **Cycles | + | **Cycle 5: 75 mg/m<sup>2</sup> IV once on day 1 |
+ | **Cycles 6 & 7: 100 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, TH portion==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 6 to 22: 6 mg/kg IV once on day 1 |
− | + | '''14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)''' | |
− | '''21-day cycle for | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #3 {{#subobject:bhgqyy|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | + | !style="width: 20%"|Study | |
− | + | !style="width: 20%"|Dates of enrollment | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
− | + | !style="width: 20%"|Comparator | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | |
− | |||
− | |||
− | |||
− | ===Regimen {{#subobject: | ||
− | {| | ||
− | | | ||
− | |[[Levels_of_Evidence#Evidence| | ||
− | | | ||
− | |[[Levels_of_Evidence# | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | |2011-2013 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#AC-THP_.28Paclitaxel.29|AC-THP (Paclitaxel)]]<br>1b. [[#AC-THP_.28Docetaxel.29_2|AC-THP (Docetaxel)]]<br>1c. [[#ddAC-THP_.28Paclitaxel.29_2|ddAC-THP (Paclitaxel)]]<br>1c. [[#ddAC-THP_.28Docetaxel.29|ddAC-THP (Docetaxel)]]<br>1e. [[#EC-THP_.28Paclitaxel.29|EC-THP (Paclitaxel)]]<br>1f. [[#EC-THP_.28Docetaxel.29|EC-THP (Docetaxel)]]<br>1g. [[#ddEC-THP_.28Paclitaxel.29|ddEC-THP (Paclitaxel)]]<br>1h. [[#ddEC-THP_.28Docetaxel.29|ddEC-THP (Docetaxel)]]<br>1i. [[#FAC-THP_.28Paclitaxel.29|FAC-THP (Paclitaxel)]]<br>1j. [[#FAC-THP_.28Docetaxel.29|FAC-THP (Docetaxel)]]<br>1k. [[#FEC-THP_.28Paclitaxel.29|FEC-THP (Paclitaxel)]]<br>1l. [[#FEC-THP_.28Docetaxel.29|FEC-THP (Docetaxel)]]<br>1m. [[#TCHP_.28Docetaxel.29_2|TCHP (Docetaxel)]] |
+ | | style="background-color:#d73027" |Inferior IDFS<sup>1</sup> | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, | + | ''Note that ranges for ddAC are given in the protocol, replicated here.'' |
− | *[[ | + | <div class="toccolours" style="background-color:#cbd5e8"> |
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, ddAC portion (cycles 1 to 4)==== | ||
+ | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Supportive therapy, ddAC portion (cycles 1 to 4)==== | |
− | ====Supportive | + | *[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] support (drug/dose/schedule not specified) |
− | *G-CSF support (drug/dose/schedule not specified) | + | ====Chemotherapy, TH portion (cycles 5 to 7)==== |
− | + | *[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1 | |
− | '''14-day cycle for 4 cycles, followed by:''' | + | ====Targeted therapy, TH portion==== |
− | + | *[[Trastuzumab (Herceptin)]] as follows: | |
− | ====Chemotherapy, | + | **Cycle 5: 8 mg/kg IV once on day 1 |
− | *[[ | + | **Cycles 6 to 22: 6 mg/kg IV once on day 1 |
− | * | + | '''14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)''' |
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''APHINITY:''' von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [https://doi.org/10.1056/NEJMoa1703643 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28581356/ PubMed] [https://clinicaltrials.gov/study/NCT01358877 NCT01358877] | ||
+ | ##'''Update:''' Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. [https://doi.org/10.1200/jco.20.01204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33539215/ PubMed] | ||
+ | ==ddAC-THP (Paclitaxel) {{#subobject:b42056|Regimen=1}}== | ||
+ | ddAC-THP: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>A</u>'''driamycin (Doxorubicin) and '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axol (Paclitaxel), '''<u>H</u>'''erceptin (Trastuzumab), '''<u>P</u>'''ertuzumab | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:b6e1ca|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-133-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2011-2013 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |1a. [[#AC-TH_.28Paclitaxel.29_2|AC-TH (Paclitaxel)]]<br>1b. [[#AC-TH_.28Docetaxel.29|AC-TH (Docetaxel)]]<br>1c. [[#ddAC-TH_.28Paclitaxel.29|ddAC-TH (Paclitaxel)]]<br>1d. [[#ddAC-TH_.28Docetaxel.29|ddAC-TH (Docetaxel)]]<br>1e. [[#EC-TH_.28Paclitaxel.29|EC-TH (Paclitaxel)]]<br>1f. [[#EC-TH_.28Docetaxel.29_2|EC-TH (Docetaxel)]]<br>1g. [[#ddEC-TH_.28Paclitaxel.29|ddEC-TH (Paclitaxel)]]<br>1h. [[#ddEC-TH_.28Docetaxel.29|ddEC-TH (Docetaxel)]]<br>1i. [[#FAC-TH_.28Paclitaxel.29|FAC-TH (Paclitaxel)]]<br>1j. [[#FAC-TH_.28Docetaxel.29|FAC-TH (Docetaxel)]]<br>1k. [[#FEC-TH_.28Paclitaxel.29_2|FEC-TH (Paclitaxel)]]<br>1l. [[#FEC-TH_.28Docetaxel.29|FEC-TH (Docetaxel)]]<br>1m. [[#TCH_.28Docetaxel.29|TCH (Taxotere)]] | ||
+ | | style="background-color:#1a9850" |Superior IDFS<sup>1</sup> (primary endpoint)<br>IDFS72: 91% vs 88%<br>(HR 0.76, 95% CI 0.64-0.91) | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ Krop et al. 2021 (KAITLIN)] | ||
+ | |2014-01 to 2015-06 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#AC-KP_999|AC-KP]]<br>1b. [[#ddAC-KP_999|ddAC-KP]]<br>1c. [[#EC-KP_999|EC-KP]]<br>1d. [[#ddEC-KP|ddEC-KP]]<br>1e. [[#FEC-KP|FEC-KP]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of IDFS | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> | ||
+ | ''Note that ranges for ddAC are given in the protocol, replicated here.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, ddAC portion (cycles 1 to 4)==== | ||
+ | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Supportive therapy, ddAC portion (cycles 1 to 4)==== | ||
+ | *[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] support (drug/dose/schedule not specified) | ||
+ | ====Chemotherapy, THP portion (cycles 5 to 8)==== | ||
+ | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | ||
+ | ====Targeted therapy, THP portion (cycles 5 to 22)==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 6 to 22: 6 mg/kg IV once on day 1 |
*[[Pertuzumab (Perjeta)]] as follows: | *[[Pertuzumab (Perjeta)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 840 mg IV once on day 1 |
− | ** | + | **Cycles 6 to 22: 420 mg IV once on day 1 |
− | + | '''14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)''' | |
− | '''21-day cycle for | + | </div></div> |
− | |||
===References=== | ===References=== | ||
− | # von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [ | + | # '''APHINITY:''' von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [https://doi.org/10.1056/NEJMoa1703643 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28581356/ PubMed] [https://clinicaltrials.gov/study/NCT01358877 NCT01358877] |
− | + | ##'''Update:''' Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. [https://doi.org/10.1200/jco.20.01204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33539215/ PubMed] | |
− | == | + | #'''KAITLIN:''' Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. [https://doi.org/10.1200/jco.21.00896 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34890214/ PubMed] [https://clinicaltrials.gov/study/NCT01966471 NCT01966471] |
− | {| class="wikitable" style=" | + | ==ddAC-THP (Docetaxel) {{#subobject:b51cf6|Regimen=1}}== |
+ | ddAC-THP: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>A</u>'''driamycin (Doxorubicin) and '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axotere (Docetaxel), '''<u>H</u>'''erceptin (Trastuzumab), '''<u>P</u>'''ertuzumab | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1 {{#subobject:b6d6yy|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-133-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2011-2013 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |1a. [[#AC-TH_.28Paclitaxel.29_2|AC-TH (Paclitaxel)]]<br>1b. [[#AC-TH_.28Docetaxel.29|AC-TH (Docetaxel)]]<br>1c. [[#ddAC-TH_.28Paclitaxel.29|ddAC-TH (Paclitaxel)]]<br>1d. [[#ddAC-TH_.28Docetaxel.29|ddAC-TH (Docetaxel)]]<br>1e. [[#EC-TH_.28Paclitaxel.29|EC-TH (Paclitaxel)]]<br>1f. [[#EC-TH_.28Docetaxel.29_2|EC-TH (Docetaxel)]]<br>1g. [[#ddEC-TH_.28Paclitaxel.29|ddEC-TH (Paclitaxel)]]<br>1h. [[#ddEC-TH_.28Docetaxel.29|ddEC-TH (Docetaxel)]]<br>1i. [[#FAC-TH_.28Paclitaxel.29|FAC-TH (Paclitaxel)]]<br>1j. [[#FAC-TH_.28Docetaxel.29|FAC-TH (Docetaxel)]]<br>1k. [[#FEC-TH_.28Paclitaxel.29_2|FEC-TH (Paclitaxel)]]<br>1l. [[#FEC-TH_.28Docetaxel.29|FEC-TH (Docetaxel)]]<br>1m. [[#TCH_.28Docetaxel.29|TCH (Taxotere)]] | ||
+ | | style="background-color:#1a9850" |Superior IDFS<sup>1</sup> (primary endpoint)<br>IDFS72: 91% vs 88%<br>(HR 0.76, 95% CI 0.64-0.91) | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ Krop et al. 2021 (KAITLIN)] | ||
+ | |2014-01 to 2015-06 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#AC-KP_999|AC-KP]]<br>1b. [[#ddAC-KP_999|ddAC-KP]]<br>1c. [[#EC-KP_999|EC-KP]]<br>1d. [[#ddEC-KP|ddEC-KP]]<br>1e. [[#FEC-KP|FEC-KP]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of IDFS | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> | |
− | ===Regimen # | + | ''Note that ranges for ddAC are given in the protocol, replicated here.'' |
− | {| | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | | | + | ====Preceding treatment==== |
− | |[[Levels_of_Evidence#Evidence| | + | *[[Surgery#Breast_cancer_surgery|Surgery]] |
− | | | + | </div> |
− | |[[Levels_of_Evidence# | + | <div class="toccolours" style="background-color:#b3e2cd"> |
+ | ====Chemotherapy, ddAC portion (cycles 1 to 4)==== | ||
+ | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Supportive therapy, ddAC portion (cycles 1 to 4)==== | ||
+ | *[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] support (drug/dose/schedule not specified) | ||
+ | ====Chemotherapy, THP portion (cycles 5 to 8)==== | ||
+ | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, THP portion (cycles 5 to 22)==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 5: 8 mg/kg IV once on day 1 | ||
+ | **Cycles 6 to 22: 6 mg/kg IV once on day 1 | ||
+ | *[[Pertuzumab (Perjeta)]] as follows: | ||
+ | **Cycle 5: 840 mg IV once on day 1 | ||
+ | **Cycles 6 to 22: 420 mg IV once on day 1 | ||
+ | '''14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2 {{#subobject:hg61yy|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" |
− | |[[# | + | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-133-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' |
− | |style="background-color:# | + | |- |
+ | |} --> | ||
+ | |2011-2013 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |1a. [[#AC-TH_.28Paclitaxel.29_2|AC-TH (Paclitaxel)]]<br>1b. [[#AC-TH_.28Docetaxel.29|AC-TH (Docetaxel)]]<br>1c. [[#ddAC-TH_.28Paclitaxel.29|ddAC-TH (Paclitaxel)]]<br>1d. [[#ddAC-TH_.28Docetaxel.29|ddAC-TH (Docetaxel)]]<br>1e. [[#EC-TH_.28Paclitaxel.29|EC-TH (Paclitaxel)]]<br>1f. [[#EC-TH_.28Docetaxel.29_2|EC-TH (Docetaxel)]]<br>1g. [[#ddEC-TH_.28Paclitaxel.29|ddEC-TH (Paclitaxel)]]<br>1h. [[#ddEC-TH_.28Docetaxel.29|ddEC-TH (Docetaxel)]]<br>1i. [[#FAC-TH_.28Paclitaxel.29|FAC-TH (Paclitaxel)]]<br>1j. [[#FAC-TH_.28Docetaxel.29|FAC-TH (Docetaxel)]]<br>1k. [[#FEC-TH_.28Paclitaxel.29_2|FEC-TH (Paclitaxel)]]<br>1l. [[#FEC-TH_.28Docetaxel.29|FEC-TH (Docetaxel)]]<br>1m. [[#TCH_.28Docetaxel.29|TCH (Taxotere)]] | ||
+ | | style="background-color:#1a9850" |Superior IDFS<sup>1</sup> (primary endpoint)<br>IDFS72: 91% vs 88%<br>(HR 0.76, 95% CI 0.64-0.91) | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ Krop et al. 2021 (KAITLIN)] | ||
+ | |2014-01 to 2015-06 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#AC-KP_999|AC-KP]]<br>1b. [[#ddAC-KP_999|ddAC-KP]]<br>1c. [[#EC-KP_999|EC-KP]]<br>1d. [[#ddEC-KP|ddEC-KP]]<br>1e. [[#FEC-KP|FEC-KP]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of IDFS | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, | + | ''Note that ranges for ddAC are given in the protocol, replicated here.'' |
− | *[[ | + | <div class="toccolours" style="background-color:#cbd5e8"> |
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, ddAC portion (cycles 1 to 4)==== | ||
+ | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Supportive therapy, ddAC portion (cycles 1 to 4)==== | |
− | ====Supportive | + | *[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] support (drug/dose/schedule not specified) |
− | *G-CSF support (drug/dose/schedule not specified) | + | ====Chemotherapy, THP portion (cycles 5 to 7)==== |
− | |||
− | |||
− | |||
− | ====Chemotherapy, THP portion==== | ||
*[[Docetaxel (Taxotere)]] as follows: | *[[Docetaxel (Taxotere)]] as follows: | ||
− | **Cycles | + | **Cycle 5: 75 mg/m<sup>2</sup> IV once on day 1 |
+ | **Cycles 6 & 7: 100 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, THP portion (cycles 5 to 22)==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 6 to 22: 6 mg/kg IV once on day 1 |
*[[Pertuzumab (Perjeta)]] as follows: | *[[Pertuzumab (Perjeta)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 840 mg IV once on day 1 |
− | ** | + | **Cycles 6 to 22: 420 mg IV once on day 1 |
− | + | '''14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)''' | |
− | '''21-day cycle for | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | ===Regimen # | + | ===Regimen variant #3 {{#subobject:bhgqry|Variant=1}}=== |
− | {| | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | | | + | !style="width: 20%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Dates of enrollment |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" |
− | |[[# | + | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-133-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' |
− | |style="background-color:# | + | |- |
+ | |} --> | ||
+ | |2011-2013 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |1a. [[#AC-TH_.28Paclitaxel.29_2|AC-TH (Paclitaxel)]]<br>1b. [[#AC-TH_.28Docetaxel.29|AC-TH (Docetaxel)]]<br>1c. [[#ddAC-TH_.28Paclitaxel.29|ddAC-TH (Paclitaxel)]]<br>1d. [[#ddAC-TH_.28Docetaxel.29|ddAC-TH (Docetaxel)]]<br>1e. [[#EC-TH_.28Paclitaxel.29|EC-TH (Paclitaxel)]]<br>1f. [[#EC-TH_.28Docetaxel.29_2|EC-TH (Docetaxel)]]<br>1g. [[#ddEC-TH_.28Paclitaxel.29|ddEC-TH (Paclitaxel)]]<br>1h. [[#ddEC-TH_.28Docetaxel.29|ddEC-TH (Docetaxel)]]<br>1i. [[#FAC-TH_.28Paclitaxel.29|FAC-TH (Paclitaxel)]]<br>1j. [[#FAC-TH_.28Docetaxel.29|FAC-TH (Docetaxel)]]<br>1k. [[#FEC-TH_.28Paclitaxel.29_2|FEC-TH (Paclitaxel)]]<br>1l. [[#FEC-TH_.28Docetaxel.29|FEC-TH (Docetaxel)]]<br>1m. [[#TCH_.28Docetaxel.29|TCH (Taxotere)]] | ||
+ | | style="background-color:#1a9850" |Superior IDFS<sup>1</sup> (primary endpoint)<br>IDFS72: 91% vs 88%<br>(HR 0.76, 95% CI 0.64-0.91) | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ Krop et al. 2021 (KAITLIN)] | ||
+ | |2014-01 to 2015-06 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#AC-KP_999|AC-KP]]<br>1b. [[#ddAC-KP_999|ddAC-KP]]<br>1c. [[#EC-KP_999|EC-KP]]<br>1d. [[#ddEC-KP|ddEC-KP]]<br>1e. [[#FEC-KP|FEC-KP]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of IDFS | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, | + | ''Note that ranges for ddAC are given in the protocol, replicated here.'' |
− | *[[ | + | <div class="toccolours" style="background-color:#cbd5e8"> |
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, ddAC portion (cycles 1 to 4)==== | ||
+ | *[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Supportive therapy, ddAC portion (cycles 1 to 4)==== | ||
+ | *[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] support (drug/dose/schedule not specified) | ||
+ | ====Chemotherapy, THP portion (cycles 5 to 7)==== | ||
+ | *[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, THP portion (cycles 5 to 22)==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 5: 8 mg/kg IV once on day 1 | ||
+ | **Cycles 6 to 22: 6 mg/kg IV once on day 1 | ||
+ | *[[Pertuzumab (Perjeta)]] as follows: | ||
+ | **Cycle 5: 840 mg IV once on day 1 | ||
+ | **Cycles 6 to 22: 420 mg IV once on day 1 | ||
+ | '''14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''APHINITY:''' von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [https://doi.org/10.1056/NEJMoa1703643 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28581356/ PubMed] [https://clinicaltrials.gov/study/NCT01358877 NCT01358877] | ||
+ | ##'''Update:''' Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. [https://doi.org/10.1200/jco.20.01204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33539215/ PubMed] | ||
+ | #'''KAITLIN:''' Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. [https://doi.org/10.1200/jco.21.00896 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34890214/ PubMed] [https://clinicaltrials.gov/study/NCT01966471 NCT01966471] | ||
+ | ==CMF-H {{#subobject:fb4c46|Regimen=1}}== | ||
+ | CMF-H: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, followed by '''<u>H</u>'''erceptin (Trastuzumab) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:1o94c2|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.20.00184 Sawaki et al. 2020 (RESPECT)] | ||
+ | |2009-10 to 2014-11 | ||
+ | | style="background-color:#1a9851" |Randomized (C) | ||
+ | |[[#Trastuzumab_monotherapy_2|Trastuzumab]] x 1 y | ||
+ | | style="background-color:#ffffbf" |Inconclusive whether non-inferior DFS (primary endpoint) | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm. The protocol document reported a flat dose of oral cyclophosphamide, but this would not be consistent with any other known CMF variants; dosing below is provided as BSA-based.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, CMF portion (cycles 1 to 6)==== | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 75 to 100 mg/m<sup>2</sup> PO once per day on days 1 to 14 | ||
+ | *[[Methotrexate (MTX)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
+ | *[[Fluorouracil (5-FU)]] 500 to 600 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
+ | ====Targeted therapy, H portion (cycles 7 to 24)==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 7: 8 mg/kg IV once on day 1 | ||
+ | **Cycles 8 to 24: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycle for 24 cycles (CMF x 6; H x 18)''' | ||
+ | </div></div> | ||
− | ==== | + | ===References=== |
− | * | + | # '''RESPECT:''' Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. [https://doi.org/10.1200/jco.20.00184 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/32936713/ PubMed] [https://clinicaltrials.gov/study/NCT01104935 NCT01104935] |
+ | ==EC-H {{#subobject:77b0fd|Regimen=1}}== | ||
+ | EC-H: '''<u>E</u>'''pirubicin and '''<u>C</u>'''yclophosphamide, followed by '''<u>H</u>'''erceptin (Trastuzumab) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:1o94c2|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.20.00184 Sawaki et al. 2020 (RESPECT)] | ||
+ | |2009-10 to 2014-11 | ||
+ | | style="background-color:#1a9851" |Randomized (C) | ||
+ | |[[#Trastuzumab_monotherapy_2|Trastuzumab]] x 1 y | ||
+ | | style="background-color:#ffffbf" |Inconclusive whether non-inferior DFS (primary endpoint) | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, EC portion (cycles 1 to 4)==== | ||
+ | *[[Epirubicin (Ellence)]] 90 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, H portion (cycles 5 to 22)==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 5: 8 mg/kg IV once on day 1 | ||
+ | **Cycles 6 to 22: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycle for 22 cycles (EC x 4; H x 18)''' | ||
+ | </div></div> | ||
− | ''' | + | ===References=== |
+ | # '''RESPECT:''' Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. [https://doi.org/10.1200/jco.20.00184 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/32936713/ PubMed] [https://clinicaltrials.gov/study/NCT01104935 NCT01104935] | ||
− | === | + | ==EC-TH (Paclitaxel) {{#subobject:ygnfj1|Regimen=1}}== |
− | + | EC-TH: '''<u>E</u>'''pirubicin and '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axol (Paclitaxel) & '''<u>H</u>'''erceptin (Trastuzumab) | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen {{#subobject:8j1v8g|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | + | !style="width: 20%"|Study | |
− | + | !style="width: 20%"|Dates of enrollment | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
− | + | !style="width: 20%"|Comparator | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | |
− | |||
− | ''' | ||
− | |||
− | ===Regimen | ||
− | {| | ||
− | | | ||
− | |[[Levels_of_Evidence#Evidence| | ||
− | | | ||
− | |[[Levels_of_Evidence# | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | |2011-2013 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#AC-THP_.28Paclitaxel.29|AC-THP (Paclitaxel)]]<br>1b. [[#AC-THP_.28Docetaxel.29_2|AC-THP (Docetaxel)]]<br>1c. [[#ddAC-THP_.28Paclitaxel.29_2|ddAC-THP (Paclitaxel)]]<br>1c. [[#ddAC-THP_.28Docetaxel.29|ddAC-THP (Docetaxel)]]<br>1e. [[#EC-THP_.28Paclitaxel.29|EC-THP (Paclitaxel)]]<br>1f. [[#EC-THP_.28Docetaxel.29|EC-THP (Docetaxel)]]<br>1g. [[#ddEC-THP_.28Paclitaxel.29|ddEC-THP (Paclitaxel)]]<br>1h. [[#ddEC-THP_.28Docetaxel.29|ddEC-THP (Docetaxel)]]<br>1i. [[#FAC-THP_.28Paclitaxel.29|FAC-THP (Paclitaxel)]]<br>1j. [[#FAC-THP_.28Docetaxel.29|FAC-THP (Docetaxel)]]<br>1k. [[#FEC-THP_.28Paclitaxel.29|FEC-THP (Paclitaxel)]]<br>1l. [[#FEC-THP_.28Docetaxel.29|FEC-THP (Docetaxel)]]<br>1m. [[#TCHP_.28Docetaxel.29_2|TCHP (Docetaxel)]] |
+ | | style="background-color:#d73027" |Inferior IDFS<sup>1</sup> | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, | + | ''Note that ranges for EC are given in the protocol, replicated here.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, EC portion (cycles 1 to 4)==== | ||
*[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | *[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Chemotherapy, TH portion (cycles 5 to 8)==== | |
− | + | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | |
− | + | ====Targeted therapy, TH portion==== | |
− | |||
− | |||
− | |||
− | ====Chemotherapy, | ||
− | *[[ | ||
− | |||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 6 to 22: 6 mg/kg IV once on day 1 |
− | + | '''21-day cycle for 22 cycles (EC x 4; TH x 4)''' | |
− | + | </div></div> | |
− | |||
− | |||
− | '''21-day cycle for | ||
− | |||
===References=== | ===References=== | ||
− | # von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [ | + | # '''APHINITY:''' von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [https://doi.org/10.1056/NEJMoa1703643 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28581356/ PubMed] [https://clinicaltrials.gov/study/NCT01358877 NCT01358877] |
+ | ##'''Update:''' Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. [https://doi.org/10.1200/jco.20.01204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33539215/ PubMed] | ||
− | ==EC - | + | ==EC-TH (Docetaxel) {{#subobject:uhg1j1|Regimen=1}}== |
− | + | EC-TH: '''<u>E</u>'''pirubicin and '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axotere (Docetaxel) & '''<u>H</u>'''erceptin (Trastuzumab) | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #1 {{#subobject:bhz7yy|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | EC - | + | !style="width: 20%"|Study |
− | ===Regimen {{#subobject: | + | !style="width: 20%"|Dates of enrollment |
− | {| | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | | | + | !style="width: 20%"|Comparator |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | | | ||
− | |[[Levels_of_Evidence# | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | |2011-2013 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#AC-THP_.28Paclitaxel.29|AC-THP (Paclitaxel)]]<br>1b. [[#AC-THP_.28Docetaxel.29_2|AC-THP (Docetaxel)]]<br>1c. [[#ddAC-THP_.28Paclitaxel.29_2|ddAC-THP (Paclitaxel)]]<br>1c. [[#ddAC-THP_.28Docetaxel.29|ddAC-THP (Docetaxel)]]<br>1e. [[#EC-THP_.28Paclitaxel.29|EC-THP (Paclitaxel)]]<br>1f. [[#EC-THP_.28Docetaxel.29|EC-THP (Docetaxel)]]<br>1g. [[#ddEC-THP_.28Paclitaxel.29|ddEC-THP (Paclitaxel)]]<br>1h. [[#ddEC-THP_.28Docetaxel.29|ddEC-THP (Docetaxel)]]<br>1i. [[#FAC-THP_.28Paclitaxel.29|FAC-THP (Paclitaxel)]]<br>1j. [[#FAC-THP_.28Docetaxel.29|FAC-THP (Docetaxel)]]<br>1k. [[#FEC-THP_.28Paclitaxel.29|FEC-THP (Paclitaxel)]]<br>1l. [[#FEC-THP_.28Docetaxel.29|FEC-THP (Docetaxel)]]<br>1m. [[#TCHP_.28Docetaxel.29_2|TCHP (Docetaxel)]] |
+ | | style="background-color:#d73027" |Inferior IDFS<sup>1</sup> | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, EC portion==== | + | ''Note that ranges for EC are given in the protocol, replicated here.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, EC portion (cycles 1 to 4)==== | ||
*[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | *[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Chemotherapy, TH portion (cycles 5 to 8)==== | |
− | + | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 | |
− | + | ====Targeted therapy, TH portion==== | |
− | ====Chemotherapy, TH portion==== | ||
− | *[[ | ||
− | |||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 6 to 22: 6 mg/kg IV once on day 1 |
− | + | '''21-day cycle for 22 cycles (EC x 4; TH x 4)''' | |
− | '''21-day cycle for | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #2 {{#subobject:hgjgvy|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | + | !style="width: 20%"|Study | |
− | + | !style="width: 20%"|Dates of enrollment | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
− | + | !style="width: 20%"|Comparator | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | |
− | |||
− | |||
− | ===Regimen # | ||
− | {| | ||
− | | | ||
− | |[[Levels_of_Evidence#Evidence| | ||
− | | | ||
− | |[[Levels_of_Evidence# | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | |2011-2013 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#AC-THP_.28Paclitaxel.29|AC-THP (Paclitaxel)]]<br>1b. [[#AC-THP_.28Docetaxel.29_2|AC-THP (Docetaxel)]]<br>1c. [[#ddAC-THP_.28Paclitaxel.29_2|ddAC-THP (Paclitaxel)]]<br>1c. [[#ddAC-THP_.28Docetaxel.29|ddAC-THP (Docetaxel)]]<br>1e. [[#EC-THP_.28Paclitaxel.29|EC-THP (Paclitaxel)]]<br>1f. [[#EC-THP_.28Docetaxel.29|EC-THP (Docetaxel)]]<br>1g. [[#ddEC-THP_.28Paclitaxel.29|ddEC-THP (Paclitaxel)]]<br>1h. [[#ddEC-THP_.28Docetaxel.29|ddEC-THP (Docetaxel)]]<br>1i. [[#FAC-THP_.28Paclitaxel.29|FAC-THP (Paclitaxel)]]<br>1j. [[#FAC-THP_.28Docetaxel.29|FAC-THP (Docetaxel)]]<br>1k. [[#FEC-THP_.28Paclitaxel.29|FEC-THP (Paclitaxel)]]<br>1l. [[#FEC-THP_.28Docetaxel.29|FEC-THP (Docetaxel)]]<br>1m. [[#TCHP_.28Docetaxel.29_2|TCHP (Docetaxel)]] |
+ | | style="background-color:#d73027" |Inferior IDFS<sup>1</sup> | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, EC portion==== | + | ''Note that ranges for EC are given in the protocol, replicated here.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, EC portion (cycles 1 to 4)==== | ||
*[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | *[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Chemotherapy, TH portion (cycles 5 to 7)==== | |
− | |||
− | |||
− | ====Chemotherapy, TH portion==== | ||
*[[Docetaxel (Taxotere)]] as follows: | *[[Docetaxel (Taxotere)]] as follows: | ||
− | **Cycles | + | **Cycle 5: 75 mg/m<sup>2</sup> IV once on day 1 |
+ | **Cycles 6 & 7: 100 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, TH portion==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 6 to 22: 6 mg/kg IV once on day 1 |
− | + | '''21-day cycle for 22 cycles (EC x 4; TH x 3)''' | |
− | '''21-day cycle for | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | ===Regimen # | + | ===Regimen variant #3 {{#subobject:bhgiu3|Variant=1}}=== |
− | {| | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | | | + | !style="width: 20%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Dates of enrollment |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | |2011-2013 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#AC-THP_.28Paclitaxel.29|AC-THP (Paclitaxel)]]<br>1b. [[#AC-THP_.28Docetaxel.29_2|AC-THP (Docetaxel)]]<br>1c. [[#ddAC-THP_.28Paclitaxel.29_2|ddAC-THP (Paclitaxel)]]<br>1c. [[#ddAC-THP_.28Docetaxel.29|ddAC-THP (Docetaxel)]]<br>1e. [[#EC-THP_.28Paclitaxel.29|EC-THP (Paclitaxel)]]<br>1f. [[#EC-THP_.28Docetaxel.29|EC-THP (Docetaxel)]]<br>1g. [[#ddEC-THP_.28Paclitaxel.29|ddEC-THP (Paclitaxel)]]<br>1h. [[#ddEC-THP_.28Docetaxel.29|ddEC-THP (Docetaxel)]]<br>1i. [[#FAC-THP_.28Paclitaxel.29|FAC-THP (Paclitaxel)]]<br>1j. [[#FAC-THP_.28Docetaxel.29|FAC-THP (Docetaxel)]]<br>1k. [[#FEC-THP_.28Paclitaxel.29|FEC-THP (Paclitaxel)]]<br>1l. [[#FEC-THP_.28Docetaxel.29|FEC-THP (Docetaxel)]]<br>1m. [[#TCHP_.28Docetaxel.29_2|TCHP (Docetaxel)]] |
+ | | style="background-color:#d73027" |Inferior IDFS<sup>1</sup> | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, EC portion==== | + | ''Note that ranges for EC are given in the protocol, replicated here.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, EC portion (cycles 1 to 4)==== | ||
*[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | *[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Chemotherapy, TH portion (cycles 5 to 7)==== | |
− | + | *[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1 | |
− | + | ====Targeted therapy, TH portion==== | |
− | ====Chemotherapy, TH portion==== | ||
− | *[[Docetaxel (Taxotere)]] | ||
− | |||
− | |||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 6 to 22: 6 mg/kg IV once on day 1 |
− | + | '''21-day cycle for 22 cycles (EC x 4; TH x 3)''' | |
− | '''21-day cycle for | + | </div></div> |
− | + | ===References=== | |
− | ===Regimen | + | # '''APHINITY:''' von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [https://doi.org/10.1056/NEJMoa1703643 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28581356/ PubMed] [https://clinicaltrials.gov/study/NCT01358877 NCT01358877] |
− | {| | + | ##'''Update:''' Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. [https://doi.org/10.1200/jco.20.01204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33539215/ PubMed] |
− | | | + | ==EC-THP (Paclitaxel) {{#subobject:ygefj1|Regimen=1}}== |
− | |[[Levels_of_Evidence#Evidence| | + | EC-THP: '''<u>E</u>'''pirubicin and '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axol (Paclitaxel), '''<u>H</u>'''erceptin (Trastuzumab), '''<u>P</u>'''ertuzumab |
− | | | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | |[[Levels_of_Evidence#Efficacy|''' | + | ===Regimen {{#subobject:8j1x8g|Variant=1}}=== |
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-133-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2011-2013 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |1a. [[#AC-TH_.28Paclitaxel.29_2|AC-TH (Paclitaxel)]]<br>1b. [[#AC-TH_.28Docetaxel.29|AC-TH (Docetaxel)]]<br>1c. [[#ddAC-TH_.28Paclitaxel.29|ddAC-TH (Paclitaxel)]]<br>1d. [[#ddAC-TH_.28Docetaxel.29|ddAC-TH (Docetaxel)]]<br>1e. [[#EC-TH_.28Paclitaxel.29|EC-TH (Paclitaxel)]]<br>1f. [[#EC-TH_.28Docetaxel.29_2|EC-TH (Docetaxel)]]<br>1g. [[#ddEC-TH_.28Paclitaxel.29|ddEC-TH (Paclitaxel)]]<br>1h. [[#ddEC-TH_.28Docetaxel.29|ddEC-TH (Docetaxel)]]<br>1i. [[#FAC-TH_.28Paclitaxel.29|FAC-TH (Paclitaxel)]]<br>1j. [[#FAC-TH_.28Docetaxel.29|FAC-TH (Docetaxel)]]<br>1k. [[#FEC-TH_.28Paclitaxel.29_2|FEC-TH (Paclitaxel)]]<br>1l. [[#FEC-TH_.28Docetaxel.29|FEC-TH (Docetaxel)]]<br>1m. [[#TCH_.28Docetaxel.29|TCH (Taxotere)]] | ||
+ | | style="background-color:#1a9850" |Superior IDFS<sup>1</sup> (primary endpoint)<br>IDFS72: 91% vs 88%<br>(HR 0.76, 95% CI 0.64-0.91) | ||
|- | |- | ||
− | |[https://www.ncbi.nlm.nih.gov/pmc/articles/ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ Krop et al. 2021 (KAITLIN)] |
− | |style="background-color:# | + | |2014-01 to 2015-06 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#AC-KP_999|AC-KP]]<br>1b. [[#ddAC-KP_999|ddAC-KP]]<br>1c. [[#EC-KP_999|EC-KP]]<br>1d. [[#ddEC-KP|ddEC-KP]]<br>1e. [[#FEC-KP|FEC-KP]] |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of IDFS | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, EC portion==== | + | ''Note that ranges for EC are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m<sup>2</sup> of epirubicin per cycle.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, EC portion (cycles 1 to 4)==== | ||
*[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | *[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Chemotherapy, THP portion (cycles 5 to 8)==== | |
− | + | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | |
− | + | ====Targeted therapy, THP portion (cycles 5 to 22)==== | |
− | ====Chemotherapy, | ||
− | *[[ | ||
− | |||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 6 to 22: 6 mg/kg IV once on day 1 |
− | + | *[[Pertuzumab (Perjeta)]] as follows: | |
− | '''21-day cycle for | + | **Cycle 5: 840 mg IV once on day 1 |
− | + | **Cycles 6 to 22: 420 mg IV once on day 1 | |
+ | '''21-day cycle for 22 cycles (EC x 4; THP x 4)''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [ | + | # '''APHINITY:''' von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [https://doi.org/10.1056/NEJMoa1703643 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28581356/ PubMed] [https://clinicaltrials.gov/study/NCT01358877 NCT01358877] |
− | + | ##'''Update:''' Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. [https://doi.org/10.1200/jco.20.01204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33539215/ PubMed] | |
− | ==EC - | + | #'''KAITLIN:''' Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. [https://doi.org/10.1200/jco.21.00896 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34890214/ PubMed] [https://clinicaltrials.gov/study/NCT01966471 NCT01966471] |
− | {| class="wikitable" style=" | + | ==EC-THP (Docetaxel) {{#subobject:vhg1j1|Regimen=1}}== |
+ | EC-THP: '''<u>E</u>'''pirubicin and '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axotere (Docetaxel), '''<u>H</u>'''erceptin (Trastuzumab), '''<u>P</u>'''ertuzumab | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1 {{#subobject:baz7yy|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-133-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2011-2013 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |1a. [[#AC-TH_.28Paclitaxel.29_2|AC-TH (Paclitaxel)]]<br>1b. [[#AC-TH_.28Docetaxel.29|AC-TH (Docetaxel)]]<br>1c. [[#ddAC-TH_.28Paclitaxel.29|ddAC-TH (Paclitaxel)]]<br>1d. [[#ddAC-TH_.28Docetaxel.29|ddAC-TH (Docetaxel)]]<br>1e. [[#EC-TH_.28Paclitaxel.29|EC-TH (Paclitaxel)]]<br>1f. [[#EC-TH_.28Docetaxel.29_2|EC-TH (Docetaxel)]]<br>1g. [[#ddEC-TH_.28Paclitaxel.29|ddEC-TH (Paclitaxel)]]<br>1h. [[#ddEC-TH_.28Docetaxel.29|ddEC-TH (Docetaxel)]]<br>1i. [[#FAC-TH_.28Paclitaxel.29|FAC-TH (Paclitaxel)]]<br>1j. [[#FAC-TH_.28Docetaxel.29|FAC-TH (Docetaxel)]]<br>1k. [[#FEC-TH_.28Paclitaxel.29_2|FEC-TH (Paclitaxel)]]<br>1l. [[#FEC-TH_.28Docetaxel.29|FEC-TH (Docetaxel)]]<br>1m. [[#TCH_.28Docetaxel.29|TCH (Taxotere)]] | ||
+ | | style="background-color:#1a9850" |Superior IDFS<sup>1</sup> (primary endpoint)<br>IDFS72: 91% vs 88%<br>(HR 0.76, 95% CI 0.64-0.91) | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ Krop et al. 2021 (KAITLIN)] | ||
+ | |2014-01 to 2015-06 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#AC-KP_999|AC-KP]]<br>1b. [[#ddAC-KP_999|ddAC-KP]]<br>1c. [[#EC-KP_999|EC-KP]]<br>1d. [[#ddEC-KP|ddEC-KP]]<br>1e. [[#FEC-KP|FEC-KP]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of IDFS | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> | |
− | + | ''Note that ranges for EC are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m<sup>2</sup> of epirubicin per cycle.'' | |
− | ===Regimen {{#subobject: | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | {| | + | ====Preceding treatment==== |
− | | | + | *[[Surgery#Breast_cancer_surgery|Surgery]] |
− | |[[Levels_of_Evidence#Evidence| | + | </div> |
− | | | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | |[[Levels_of_Evidence# | + | ====Chemotherapy, EC portion (cycles 1 to 4)==== |
+ | *[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Chemotherapy, THP portion (cycles 5 to 8)==== | ||
+ | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, THP portion (cycles 5 to 22)==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 5: 8 mg/kg IV once on day 1 | ||
+ | **Cycles 6 to 22: 6 mg/kg IV once on day 1 | ||
+ | *[[Pertuzumab (Perjeta)]] as follows: | ||
+ | **Cycle 5: 840 mg IV once on day 1 | ||
+ | **Cycles 6 to 22: 420 mg IV once on day 1 | ||
+ | '''21-day cycle for 22 cycles (EC x 4; THP x 4)''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2 {{#subobject:hgtgvy|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" |
− | |[[# | + | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-133-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' |
− | |style="background-color:# | + | |- |
+ | |} --> | ||
+ | |2011-2013 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |1a. [[#AC-TH_.28Paclitaxel.29_2|AC-TH (Paclitaxel)]]<br>1b. [[#AC-TH_.28Docetaxel.29|AC-TH (Docetaxel)]]<br>1c. [[#ddAC-TH_.28Paclitaxel.29|ddAC-TH (Paclitaxel)]]<br>1d. [[#ddAC-TH_.28Docetaxel.29|ddAC-TH (Docetaxel)]]<br>1e. [[#EC-TH_.28Paclitaxel.29|EC-TH (Paclitaxel)]]<br>1f. [[#EC-TH_.28Docetaxel.29_2|EC-TH (Docetaxel)]]<br>1g. [[#ddEC-TH_.28Paclitaxel.29|ddEC-TH (Paclitaxel)]]<br>1h. [[#ddEC-TH_.28Docetaxel.29|ddEC-TH (Docetaxel)]]<br>1i. [[#FAC-TH_.28Paclitaxel.29|FAC-TH (Paclitaxel)]]<br>1j. [[#FAC-TH_.28Docetaxel.29|FAC-TH (Docetaxel)]]<br>1k. [[#FEC-TH_.28Paclitaxel.29_2|FEC-TH (Paclitaxel)]]<br>1l. [[#FEC-TH_.28Docetaxel.29|FEC-TH (Docetaxel)]]<br>1m. [[#TCH_.28Docetaxel.29|TCH (Taxotere)]] | ||
+ | | style="background-color:#1a9850" |Superior IDFS<sup>1</sup> (primary endpoint)<br>IDFS72: 91% vs 88%<br>(HR 0.76, 95% CI 0.64-0.91) | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ Krop et al. 2021 (KAITLIN)] | ||
+ | |2014-01 to 2015-06 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#AC-KP_999|AC-KP]]<br>1b. [[#ddAC-KP_999|ddAC-KP]]<br>1c. [[#EC-KP_999|EC-KP]]<br>1d. [[#ddEC-KP|ddEC-KP]]<br>1e. [[#FEC-KP|FEC-KP]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of IDFS | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, EC portion==== | + | ''Note that ranges for EC are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m<sup>2</sup> of epirubicin per cycle.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, EC portion (cycles 1 to 4)==== | ||
*[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | *[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Chemotherapy, THP portion (cycles 5 to 7)==== | |
− | + | *[[Docetaxel (Taxotere)]] as follows: | |
− | + | **Cycle 5: 75 mg/m<sup>2</sup> IV once on day 1 | |
− | ====Chemotherapy, THP portion==== | + | **Cycles 6 & 7: 100 mg/m<sup>2</sup> IV once on day 1 |
− | *[[ | + | ====Targeted therapy, THP portion (cycles 5 to 22)==== |
− | ** | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 6 to 22: 6 mg/kg IV once on day 1 |
*[[Pertuzumab (Perjeta)]] as follows: | *[[Pertuzumab (Perjeta)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 840 mg IV once on day 1 |
− | ** | + | **Cycles 6 to 22: 420 mg IV once on day 1 |
− | + | '''21-day cycle for 22 cycles (EC x 4; THP x 3)''' | |
− | '''21-day cycle for | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | === | + | ===Regimen variant #3 {{#subobject:bhhiu3|Variant=1}}=== |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | + | !style="width: 20%"|Study | |
− | + | !style="width: 20%"|Dates of enrollment | |
− | {| class="wikitable" style=" | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-133-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' | ||
|- | |- | ||
− | |[[# | + | |} --> |
− | | | + | |2011-2013 |
− | + | |style="background-color:#1a9851"|Phase 3 (E-esc) | |
− | + | |1a. [[#AC-TH_.28Paclitaxel.29_2|AC-TH (Paclitaxel)]]<br>1b. [[#AC-TH_.28Docetaxel.29|AC-TH (Docetaxel)]]<br>1c. [[#ddAC-TH_.28Paclitaxel.29|ddAC-TH (Paclitaxel)]]<br>1d. [[#ddAC-TH_.28Docetaxel.29|ddAC-TH (Docetaxel)]]<br>1e. [[#EC-TH_.28Paclitaxel.29|EC-TH (Paclitaxel)]]<br>1f. [[#EC-TH_.28Docetaxel.29_2|EC-TH (Docetaxel)]]<br>1g. [[#ddEC-TH_.28Paclitaxel.29|ddEC-TH (Paclitaxel)]]<br>1h. [[#ddEC-TH_.28Docetaxel.29|ddEC-TH (Docetaxel)]]<br>1i. [[#FAC-TH_.28Paclitaxel.29|FAC-TH (Paclitaxel)]]<br>1j. [[#FAC-TH_.28Docetaxel.29|FAC-TH (Docetaxel)]]<br>1k. [[#FEC-TH_.28Paclitaxel.29_2|FEC-TH (Paclitaxel)]]<br>1l. [[#FEC-TH_.28Docetaxel.29|FEC-TH (Docetaxel)]]<br>1m. [[#TCH_.28Docetaxel.29|TCH (Taxotere)]] | |
− | + | | style="background-color:#1a9850" |Superior IDFS<sup>1</sup> (primary endpoint)<br>IDFS72: 91% vs 88%<br>(HR 0.76, 95% CI 0.64-0.91) | |
− | |||
− | |||
− | | | ||
− | |||
|- | |- | ||
− | |[https://www.ncbi.nlm.nih.gov/pmc/articles/ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ Krop et al. 2021 (KAITLIN)] |
− | |style="background-color:# | + | |2014-01 to 2015-06 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#AC-KP_999|AC-KP]]<br>1b. [[#ddAC-KP_999|ddAC-KP]]<br>1c. [[#EC-KP_999|EC-KP]]<br>1d. [[#ddEC-KP|ddEC-KP]]<br>1e. [[#FEC-KP|FEC-KP]] |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of IDFS | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, EC portion==== | + | ''Note that ranges for EC are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m<sup>2</sup> of epirubicin per cycle.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, EC portion (cycles 1 to 4)==== | ||
*[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | *[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Chemotherapy, THP portion (cycles 5 to 7)==== | |
− | + | *[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1 | |
− | + | ====Targeted therapy, THP portion (cycles 5 to 22)==== | |
− | ====Chemotherapy, THP portion==== | ||
− | *[[Docetaxel (Taxotere)]] | ||
− | |||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 6 to 22: 6 mg/kg IV once on day 1 |
*[[Pertuzumab (Perjeta)]] as follows: | *[[Pertuzumab (Perjeta)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 840 mg IV once on day 1 |
− | ** | + | **Cycles 6 to 22: 420 mg IV once on day 1 |
− | + | '''21-day cycle for 22 cycles (EC x 4; THP x 3)''' | |
− | '''21-day cycle for | + | </div></div> |
− | + | ===References=== | |
− | ===Regimen | + | # '''APHINITY:''' von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [https://doi.org/10.1056/NEJMoa1703643 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28581356/ PubMed] [https://clinicaltrials.gov/study/NCT01358877 NCT01358877] |
− | {| | + | ##'''Update:''' Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. [https://doi.org/10.1200/jco.20.01204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33539215/ PubMed] |
− | | | + | #'''KAITLIN:''' Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. [https://doi.org/10.1200/jco.21.00896 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34890214/ PubMed] [https://clinicaltrials.gov/study/NCT01966471 NCT01966471] |
− | |[[Levels_of_Evidence#Evidence| | + | ==ddEC-TH (Paclitaxel) {{#subobject:yubm11|Regimen=1}}== |
− | | | + | ddEC-TH: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>E</u>'''pirubicin and '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axol (Paclitaxel) & '''<u>H</u>'''erceptin (Trastuzumab) |
− | |[[Levels_of_Evidence# | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen {{#subobject:9ishbg|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | |2011-2013 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#AC-THP_.28Paclitaxel.29|AC-THP (Paclitaxel)]]<br>1b. [[#AC-THP_.28Docetaxel.29_2|AC-THP (Docetaxel)]]<br>1c. [[#ddAC-THP_.28Paclitaxel.29_2|ddAC-THP (Paclitaxel)]]<br>1c. [[#ddAC-THP_.28Docetaxel.29|ddAC-THP (Docetaxel)]]<br>1e. [[#EC-THP_.28Paclitaxel.29|EC-THP (Paclitaxel)]]<br>1f. [[#EC-THP_.28Docetaxel.29|EC-THP (Docetaxel)]]<br>1g. [[#ddEC-THP_.28Paclitaxel.29|ddEC-THP (Paclitaxel)]]<br>1h. [[#ddEC-THP_.28Docetaxel.29|ddEC-THP (Docetaxel)]]<br>1i. [[#FAC-THP_.28Paclitaxel.29|FAC-THP (Paclitaxel)]]<br>1j. [[#FAC-THP_.28Docetaxel.29|FAC-THP (Docetaxel)]]<br>1k. [[#FEC-THP_.28Paclitaxel.29|FEC-THP (Paclitaxel)]]<br>1l. [[#FEC-THP_.28Docetaxel.29|FEC-THP (Docetaxel)]]<br>1m. [[#TCHP_.28Docetaxel.29_2|TCHP (Docetaxel)]] |
+ | | style="background-color:#d73027" |Inferior IDFS<sup>1</sup> | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, | + | ''Note that ranges for ddEC are given in the protocol, replicated here.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, ddEC portion (cycles 1 to 4)==== | ||
*[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | *[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Supportive therapy, ddEC portion (cycles 1 to 4)==== | |
− | '''21-day cycle for 4 | + | *[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] support (drug/dose/schedule not specified) |
− | + | ====Chemotherapy, TH portion (cycles 5 to 8)==== | |
− | ====Chemotherapy, | + | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 |
− | *[[ | + | ====Targeted therapy, TH portion==== |
− | * | + | *[[Trastuzumab (Herceptin)]] as follows: |
− | ** | + | **Cycle 5: 8 mg/kg IV once on day 1 |
+ | **Cycles 6 to 22: 6 mg/kg IV once on day 1 | ||
+ | '''14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''APHINITY:''' von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [https://doi.org/10.1056/NEJMoa1703643 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28581356/ PubMed] [https://clinicaltrials.gov/study/NCT01358877 NCT01358877] | ||
+ | ##'''Update:''' Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. [https://doi.org/10.1200/jco.20.01204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33539215/ PubMed] | ||
+ | ==ddEC-TH (Docetaxel) {{#subobject:yuhb51|Regimen=1}}== | ||
+ | ddEC-TH: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>E</u>'''pirubicin and '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axotere (Docetaxel) & '''<u>H</u>'''erceptin (Trastuzumab) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1 {{#subobject:b4jmfy|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
+ | |2011-2013 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#AC-THP_.28Paclitaxel.29|AC-THP (Paclitaxel)]]<br>1b. [[#AC-THP_.28Docetaxel.29_2|AC-THP (Docetaxel)]]<br>1c. [[#ddAC-THP_.28Paclitaxel.29_2|ddAC-THP (Paclitaxel)]]<br>1c. [[#ddAC-THP_.28Docetaxel.29|ddAC-THP (Docetaxel)]]<br>1e. [[#EC-THP_.28Paclitaxel.29|EC-THP (Paclitaxel)]]<br>1f. [[#EC-THP_.28Docetaxel.29|EC-THP (Docetaxel)]]<br>1g. [[#ddEC-THP_.28Paclitaxel.29|ddEC-THP (Paclitaxel)]]<br>1h. [[#ddEC-THP_.28Docetaxel.29|ddEC-THP (Docetaxel)]]<br>1i. [[#FAC-THP_.28Paclitaxel.29|FAC-THP (Paclitaxel)]]<br>1j. [[#FAC-THP_.28Docetaxel.29|FAC-THP (Docetaxel)]]<br>1k. [[#FEC-THP_.28Paclitaxel.29|FEC-THP (Paclitaxel)]]<br>1l. [[#FEC-THP_.28Docetaxel.29|FEC-THP (Docetaxel)]]<br>1m. [[#TCHP_.28Docetaxel.29_2|TCHP (Docetaxel)]] | ||
+ | | style="background-color:#d73027" |Inferior IDFS<sup>1</sup> | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> | ||
+ | ''Note that ranges for ddEC are given in the protocol, replicated here.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, ddEC portion (cycles 1 to 4)==== | ||
+ | *[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Supportive therapy, ddEC portion (cycles 1 to 4)==== | ||
+ | *[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] support (drug/dose/schedule not specified) | ||
+ | ====Chemotherapy, TH portion (cycles 5 to 8)==== | ||
+ | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, TH portion==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 6 to 22: 6 mg/kg IV once on day 1 |
− | + | '''14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)''' | |
− | + | </div></div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #2 {{#subobject:hgjg32|Variant=1}}=== | |
− | '''21-day cycle for | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | + | !style="width: 20%"|Study | |
− | ===Regimen # | + | !style="width: 20%"|Dates of enrollment |
− | {| | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | | | + | !style="width: 20%"|Comparator |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | | | ||
− | |[[Levels_of_Evidence# | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | |2011-2013 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#AC-THP_.28Paclitaxel.29|AC-THP (Paclitaxel)]]<br>1b. [[#AC-THP_.28Docetaxel.29_2|AC-THP (Docetaxel)]]<br>1c. [[#ddAC-THP_.28Paclitaxel.29_2|ddAC-THP (Paclitaxel)]]<br>1c. [[#ddAC-THP_.28Docetaxel.29|ddAC-THP (Docetaxel)]]<br>1e. [[#EC-THP_.28Paclitaxel.29|EC-THP (Paclitaxel)]]<br>1f. [[#EC-THP_.28Docetaxel.29|EC-THP (Docetaxel)]]<br>1g. [[#ddEC-THP_.28Paclitaxel.29|ddEC-THP (Paclitaxel)]]<br>1h. [[#ddEC-THP_.28Docetaxel.29|ddEC-THP (Docetaxel)]]<br>1i. [[#FAC-THP_.28Paclitaxel.29|FAC-THP (Paclitaxel)]]<br>1j. [[#FAC-THP_.28Docetaxel.29|FAC-THP (Docetaxel)]]<br>1k. [[#FEC-THP_.28Paclitaxel.29|FEC-THP (Paclitaxel)]]<br>1l. [[#FEC-THP_.28Docetaxel.29|FEC-THP (Docetaxel)]]<br>1m. [[#TCHP_.28Docetaxel.29_2|TCHP (Docetaxel)]] |
+ | | style="background-color:#d73027" |Inferior IDFS<sup>1</sup> | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, | + | ''Note that ranges for ddEC are given in the protocol, replicated here.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, ddEC portion (cycles 1 to 4)==== | ||
*[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | *[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Supportive therapy, ddEC portion (cycles 1 to 4)==== | |
− | + | *[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] support (drug/dose/schedule not specified) | |
− | + | ====Chemotherapy, TH portion==== | |
− | ====Chemotherapy, | ||
*[[Docetaxel (Taxotere)]] as follows: | *[[Docetaxel (Taxotere)]] as follows: | ||
− | **Cycles | + | **Cycle 5: 75 mg/m<sup>2</sup> IV once on day 1 |
+ | **Cycles 6 & 7: 100 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, TH portion==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 6 to 22: 6 mg/kg IV once on day 1 |
− | + | '''14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)''' | |
− | + | </div></div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #3 {{#subobject:bhgyt2|Variant=1}}=== | |
− | '''21-day cycle for | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | + | !style="width: 20%"|Study | |
− | === | + | !style="width: 20%"|Dates of enrollment |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
− | + | !style="width: 20%"|Comparator | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | |
− | + | |- | |
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
+ | |2011-2013 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#AC-THP_.28Paclitaxel.29|AC-THP (Paclitaxel)]]<br>1b. [[#AC-THP_.28Docetaxel.29_2|AC-THP (Docetaxel)]]<br>1c. [[#ddAC-THP_.28Paclitaxel.29_2|ddAC-THP (Paclitaxel)]]<br>1c. [[#ddAC-THP_.28Docetaxel.29|ddAC-THP (Docetaxel)]]<br>1e. [[#EC-THP_.28Paclitaxel.29|EC-THP (Paclitaxel)]]<br>1f. [[#EC-THP_.28Docetaxel.29|EC-THP (Docetaxel)]]<br>1g. [[#ddEC-THP_.28Paclitaxel.29|ddEC-THP (Paclitaxel)]]<br>1h. [[#ddEC-THP_.28Docetaxel.29|ddEC-THP (Docetaxel)]]<br>1i. [[#FAC-THP_.28Paclitaxel.29|FAC-THP (Paclitaxel)]]<br>1j. [[#FAC-THP_.28Docetaxel.29|FAC-THP (Docetaxel)]]<br>1k. [[#FEC-THP_.28Paclitaxel.29|FEC-THP (Paclitaxel)]]<br>1l. [[#FEC-THP_.28Docetaxel.29|FEC-THP (Docetaxel)]]<br>1m. [[#TCHP_.28Docetaxel.29_2|TCHP (Docetaxel)]] | ||
+ | | style="background-color:#d73027" |Inferior IDFS<sup>1</sup> | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> | |
− | ===Regimen {{#subobject: | + | ''Note that ranges for ddEC are given in the protocol, replicated here.'' |
− | {| | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | | | + | ====Preceding treatment==== |
− | |[[Levels_of_Evidence#Evidence| | + | *[[Surgery#Breast_cancer_surgery|Surgery]] |
− | | | + | </div> |
− | |[[Levels_of_Evidence# | + | <div class="toccolours" style="background-color:#b3e2cd"> |
+ | ====Chemotherapy, ddEC portion (cycles 1 to 4)==== | ||
+ | *[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Supportive therapy, ddEC portion (cycles 1 to 4)==== | ||
+ | *[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] support (drug/dose/schedule not specified) | ||
+ | ====Chemotherapy, TH portion (cycles 5 to 7)==== | ||
+ | *[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, TH portion==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 5: 8 mg/kg IV once on day 1 | ||
+ | **Cycles 6 to 22: 6 mg/kg IV once on day 1 | ||
+ | '''14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''APHINITY:''' von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [https://doi.org/10.1056/NEJMoa1703643 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28581356/ PubMed] [https://clinicaltrials.gov/study/NCT01358877 NCT01358877] | ||
+ | ##'''Update:''' Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. [https://doi.org/10.1200/jco.20.01204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33539215/ PubMed] | ||
+ | ==ddEC-THP (Paclitaxel) {{#subobject:ytbm11|Regimen=1}}== | ||
+ | ddEC-THP: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>E</u>'''pirubicin and '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axol (Paclitaxel), '''<u>H</u>'''erceptin (Trastuzumab), '''<u>P</u>'''ertuzumab | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:9isibg|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" |
− | |[[# | + | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-133-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' |
− | |style="background-color:# | + | |- |
+ | |} --> | ||
+ | |2011-2013 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |1a. [[#AC-TH_.28Paclitaxel.29_2|AC-TH (Paclitaxel)]]<br>1b. [[#AC-TH_.28Docetaxel.29|AC-TH (Docetaxel)]]<br>1c. [[#ddAC-TH_.28Paclitaxel.29|ddAC-TH (Paclitaxel)]]<br>1d. [[#ddAC-TH_.28Docetaxel.29|ddAC-TH (Docetaxel)]]<br>1e. [[#EC-TH_.28Paclitaxel.29|EC-TH (Paclitaxel)]]<br>1f. [[#EC-TH_.28Docetaxel.29_2|EC-TH (Docetaxel)]]<br>1g. [[#ddEC-TH_.28Paclitaxel.29|ddEC-TH (Paclitaxel)]]<br>1h. [[#ddEC-TH_.28Docetaxel.29|ddEC-TH (Docetaxel)]]<br>1i. [[#FAC-TH_.28Paclitaxel.29|FAC-TH (Paclitaxel)]]<br>1j. [[#FAC-TH_.28Docetaxel.29|FAC-TH (Docetaxel)]]<br>1k. [[#FEC-TH_.28Paclitaxel.29_2|FEC-TH (Paclitaxel)]]<br>1l. [[#FEC-TH_.28Docetaxel.29|FEC-TH (Docetaxel)]]<br>1m. [[#TCH_.28Docetaxel.29|TCH (Taxotere)]] | ||
+ | | style="background-color:#1a9850" |Superior IDFS<sup>1</sup> (primary endpoint)<br>IDFS72: 91% vs 88%<br>(HR 0.76, 95% CI 0.64-0.91) | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ Krop et al. 2021 (KAITLIN)] | ||
+ | |2014-01 to 2015-06 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#AC-KP_999|AC-KP]]<br>1b. [[#ddAC-KP_999|ddAC-KP]]<br>1c. [[#EC-KP_999|EC-KP]]<br>1d. [[#ddEC-KP|ddEC-KP]]<br>1e. [[#FEC-KP|FEC-KP]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of IDFS | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ==== | + | ''Note that ranges for ddEC are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m<sup>2</sup> of epirubicin per cycle.'' |
− | *[[ | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | *[[ | + | ====Preceding treatment==== |
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, ddEC portion (cycles 1 to 4)==== | ||
+ | *[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Supportive therapy, ddEC portion (cycles 1 to 4)==== | |
− | + | *[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] support (drug/dose/schedule not specified) | |
− | + | ====Chemotherapy, THP portion (cycles 5 to 8)==== | |
− | ====Chemotherapy, | + | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 |
− | *[[Paclitaxel (Taxol)]] | + | ====Targeted therapy, THP portion (cycles 5 to 22)==== |
− | |||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 6 to 22: 6 mg/kg IV once on day 1 |
− | + | *[[Pertuzumab (Perjeta)]] as follows: | |
− | '''21-day cycle for | + | **Cycle 5: 840 mg IV once on day 1 |
− | + | **Cycles 6 to 22: 420 mg IV once on day 1 | |
+ | '''14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [ | + | # '''APHINITY:''' von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [https://doi.org/10.1056/NEJMoa1703643 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28581356/ PubMed] [https://clinicaltrials.gov/study/NCT01358877 NCT01358877] |
− | + | ##'''Update:''' Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. [https://doi.org/10.1200/jco.20.01204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33539215/ PubMed] | |
− | == | + | #'''KAITLIN:''' Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. [https://doi.org/10.1200/jco.21.00896 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34890214/ PubMed] [https://clinicaltrials.gov/study/NCT01966471 NCT01966471] |
− | + | ==ddEC-THP (Docetaxel) {{#subobject:guhb51|Regimen=1}}== | |
− | + | ddEC-THP: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>E</u>'''pirubicin and '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axotere (Docetaxel), '''<u>H</u>'''erceptin (Trastuzumab), '''<u>P</u>'''ertuzumab | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #1 {{#subobject:r4jmfy|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | ===Regimen #1 {{#subobject: | + | !style="width: 20%"|Study |
− | {| | + | !style="width: 20%"|Dates of enrollment |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Comparator |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | |[[Levels_of_Evidence# | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" |
− | |[[# | + | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-133-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' |
− | |style="background-color:# | + | |- |
+ | |} --> | ||
+ | |2011-2013 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |1a. [[#AC-TH_.28Paclitaxel.29_2|AC-TH (Paclitaxel)]]<br>1b. [[#AC-TH_.28Docetaxel.29|AC-TH (Docetaxel)]]<br>1c. [[#ddAC-TH_.28Paclitaxel.29|ddAC-TH (Paclitaxel)]]<br>1d. [[#ddAC-TH_.28Docetaxel.29|ddAC-TH (Docetaxel)]]<br>1e. [[#EC-TH_.28Paclitaxel.29|EC-TH (Paclitaxel)]]<br>1f. [[#EC-TH_.28Docetaxel.29_2|EC-TH (Docetaxel)]]<br>1g. [[#ddEC-TH_.28Paclitaxel.29|ddEC-TH (Paclitaxel)]]<br>1h. [[#ddEC-TH_.28Docetaxel.29|ddEC-TH (Docetaxel)]]<br>1i. [[#FAC-TH_.28Paclitaxel.29|FAC-TH (Paclitaxel)]]<br>1j. [[#FAC-TH_.28Docetaxel.29|FAC-TH (Docetaxel)]]<br>1k. [[#FEC-TH_.28Paclitaxel.29_2|FEC-TH (Paclitaxel)]]<br>1l. [[#FEC-TH_.28Docetaxel.29|FEC-TH (Docetaxel)]]<br>1m. [[#TCH_.28Docetaxel.29|TCH (Taxotere)]] | ||
+ | | style="background-color:#1a9850" |Superior IDFS<sup>1</sup> (primary endpoint)<br>IDFS72: 91% vs 88%<br>(HR 0.76, 95% CI 0.64-0.91) | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ Krop et al. 2021 (KAITLIN)] | ||
+ | |2014-01 to 2015-06 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#AC-KP_999|AC-KP]]<br>1b. [[#ddAC-KP_999|ddAC-KP]]<br>1c. [[#EC-KP_999|EC-KP]]<br>1d. [[#ddEC-KP|ddEC-KP]]<br>1e. [[#FEC-KP|FEC-KP]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of IDFS | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ==== | + | ''Note that ranges for ddEC are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m<sup>2</sup> of epirubicin per cycle.'' |
− | *[[ | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | *[[ | + | ====Preceding treatment==== |
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, ddEC portion (cycles 1 to 4)==== | ||
+ | *[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Supportive therapy, ddEC portion (cycles 1 to 4)==== | |
− | + | *[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] support (drug/dose/schedule not specified) | |
− | + | ====Chemotherapy, THP portion (cycles 5 to 8)==== | |
− | ====Chemotherapy, | + | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Docetaxel (Taxotere)]] | + | ====Targeted therapy, THP portion (cycles 5 to 22)==== |
− | |||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 6 to 22: 6 mg/kg IV once on day 1 |
− | + | *[[Pertuzumab (Perjeta)]] as follows: | |
− | '''21-day cycle for | + | **Cycle 5: 840 mg IV once on day 1 |
− | + | **Cycles 6 to 22: 420 mg IV once on day 1 | |
− | ===Regimen #2 {{#subobject: | + | '''14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)''' |
− | {| | + | </div></div><br> |
− | | | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | |[[Levels_of_Evidence#Evidence| | + | ===Regimen variant #2 {{#subobject:h4jg32|Variant=1}}=== |
− | | | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|Study |
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" |
− | |[[# | + | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-133-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' |
− | |style="background-color:# | + | |- |
+ | |} --> | ||
+ | |2011-2013 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |1a. [[#AC-TH_.28Paclitaxel.29_2|AC-TH (Paclitaxel)]]<br>1b. [[#AC-TH_.28Docetaxel.29|AC-TH (Docetaxel)]]<br>1c. [[#ddAC-TH_.28Paclitaxel.29|ddAC-TH (Paclitaxel)]]<br>1d. [[#ddAC-TH_.28Docetaxel.29|ddAC-TH (Docetaxel)]]<br>1e. [[#EC-TH_.28Paclitaxel.29|EC-TH (Paclitaxel)]]<br>1f. [[#EC-TH_.28Docetaxel.29_2|EC-TH (Docetaxel)]]<br>1g. [[#ddEC-TH_.28Paclitaxel.29|ddEC-TH (Paclitaxel)]]<br>1h. [[#ddEC-TH_.28Docetaxel.29|ddEC-TH (Docetaxel)]]<br>1i. [[#FAC-TH_.28Paclitaxel.29|FAC-TH (Paclitaxel)]]<br>1j. [[#FAC-TH_.28Docetaxel.29|FAC-TH (Docetaxel)]]<br>1k. [[#FEC-TH_.28Paclitaxel.29_2|FEC-TH (Paclitaxel)]]<br>1l. [[#FEC-TH_.28Docetaxel.29|FEC-TH (Docetaxel)]]<br>1m. [[#TCH_.28Docetaxel.29|TCH (Taxotere)]] | ||
+ | | style="background-color:#1a9850" |Superior IDFS<sup>1</sup> (primary endpoint)<br>IDFS72: 91% vs 88%<br>(HR 0.76, 95% CI 0.64-0.91) | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ Krop et al. 2021 (KAITLIN)] | ||
+ | |2014-01 to 2015-06 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#AC-KP_999|AC-KP]]<br>1b. [[#ddAC-KP_999|ddAC-KP]]<br>1c. [[#EC-KP_999|EC-KP]]<br>1d. [[#ddEC-KP|ddEC-KP]]<br>1e. [[#FEC-KP|FEC-KP]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of IDFS | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ==== | + | ''Note that ranges for ddEC are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m<sup>2</sup> of epirubicin per cycle.'' |
− | *[[ | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | *[[ | + | ====Preceding treatment==== |
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, ddEC portion (cycles 1 to 4)==== | ||
+ | *[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Supportive therapy, ddEC portion (cycles 1 to 4)==== | |
− | + | *[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] support (drug/dose/schedule not specified) | |
− | + | ====Chemotherapy, THP portion (cycles 5 to 7)==== | |
− | ====Chemotherapy, | ||
*[[Docetaxel (Taxotere)]] as follows: | *[[Docetaxel (Taxotere)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 75 mg/m<sup>2</sup> IV once on day 1 |
− | **Cycles | + | **Cycles 6 & 7: 100 mg/m<sup>2</sup> IV once on day 1 |
+ | ====Targeted therapy, THP portion (cycles 5 to 22)==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 5: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 6 to 22: 6 mg/kg IV once on day 1 |
− | + | *[[Pertuzumab (Perjeta)]] as follows: | |
− | '''21-day cycle for | + | **Cycle 5: 840 mg IV once on day 1 |
− | + | **Cycles 6 to 22: 420 mg IV once on day 1 | |
− | ===Regimen #3 {{#subobject: | + | '''14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)''' |
− | {| | + | </div></div><br> |
− | |''' | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | |[[ | + | ===Regimen variant #3 {{#subobject:bhg4t2|Variant=1}}=== |
− | |''' | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | + | !style="width: 20%"|Study | |
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-133-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2011-2013 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |1a. [[#AC-TH_.28Paclitaxel.29_2|AC-TH (Paclitaxel)]]<br>1b. [[#AC-TH_.28Docetaxel.29|AC-TH (Docetaxel)]]<br>1c. [[#ddAC-TH_.28Paclitaxel.29|ddAC-TH (Paclitaxel)]]<br>1d. [[#ddAC-TH_.28Docetaxel.29|ddAC-TH (Docetaxel)]]<br>1e. [[#EC-TH_.28Paclitaxel.29|EC-TH (Paclitaxel)]]<br>1f. [[#EC-TH_.28Docetaxel.29_2|EC-TH (Docetaxel)]]<br>1g. [[#ddEC-TH_.28Paclitaxel.29|ddEC-TH (Paclitaxel)]]<br>1h. [[#ddEC-TH_.28Docetaxel.29|ddEC-TH (Docetaxel)]]<br>1i. [[#FAC-TH_.28Paclitaxel.29|FAC-TH (Paclitaxel)]]<br>1j. [[#FAC-TH_.28Docetaxel.29|FAC-TH (Docetaxel)]]<br>1k. [[#FEC-TH_.28Paclitaxel.29_2|FEC-TH (Paclitaxel)]]<br>1l. [[#FEC-TH_.28Docetaxel.29|FEC-TH (Docetaxel)]]<br>1m. [[#TCH_.28Docetaxel.29|TCH (Taxotere)]] | ||
+ | | style="background-color:#1a9850" |Superior IDFS<sup>1</sup> (primary endpoint)<br>IDFS72: 91% vs 88%<br>(HR 0.76, 95% CI 0.64-0.91) | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ Krop et al. 2021 (KAITLIN)] | ||
+ | |2014-01 to 2015-06 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#AC-KP_999|AC-KP]]<br>1b. [[#ddAC-KP_999|ddAC-KP]]<br>1c. [[#EC-KP_999|EC-KP]]<br>1d. [[#ddEC-KP|ddEC-KP]]<br>1e. [[#FEC-KP|FEC-KP]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of IDFS | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> | ||
+ | ''Note that ranges for ddEC are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m<sup>2</sup> of epirubicin per cycle.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, ddEC portion (cycles 1 to 4)==== | ||
+ | *[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Supportive therapy, ddEC portion (cycles 1 to 4)==== | ||
+ | *[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] support (drug/dose/schedule not specified) | ||
+ | ====Chemotherapy, THP portion (cycles 5 to 7)==== | ||
+ | *[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, THP portion (cycles 5 to 22)==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 5: 8 mg/kg IV once on day 1 | ||
+ | **Cycles 6 to 22: 6 mg/kg IV once on day 1 | ||
+ | *[[Pertuzumab (Perjeta)]] as follows: | ||
+ | **Cycle 5: 840 mg IV once on day 1 | ||
+ | **Cycles 6 to 22: 420 mg IV once on day 1 | ||
+ | '''14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''APHINITY:''' von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [https://doi.org/10.1056/NEJMoa1703643 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28581356/ PubMed] [https://clinicaltrials.gov/study/NCT01358877 NCT01358877] | ||
+ | ##'''Update:''' Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. [https://doi.org/10.1200/jco.20.01204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33539215/ PubMed] | ||
+ | #'''KAITLIN:''' Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. [https://doi.org/10.1200/jco.21.00896 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34890214/ PubMed] [https://clinicaltrials.gov/study/NCT01966471 NCT01966471] | ||
+ | ==FAC-TH (Paclitaxel) {{#subobject:u88g11|Regimen=1}}== | ||
+ | FAC-TH: '''<u>F</u>'''luorouracil, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axol (Paclitaxel) & '''<u>H</u>'''erceptin (Trastuzumab) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:9uhqrg|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | |2011-2013 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#AC-THP_.28Paclitaxel.29|AC-THP (Paclitaxel)]]<br>1b. [[#AC-THP_.28Docetaxel.29_2|AC-THP (Docetaxel)]]<br>1c. [[#ddAC-THP_.28Paclitaxel.29_2|ddAC-THP (Paclitaxel)]]<br>1c. [[#ddAC-THP_.28Docetaxel.29|ddAC-THP (Docetaxel)]]<br>1e. [[#EC-THP_.28Paclitaxel.29|EC-THP (Paclitaxel)]]<br>1f. [[#EC-THP_.28Docetaxel.29|EC-THP (Docetaxel)]]<br>1g. [[#ddEC-THP_.28Paclitaxel.29|ddEC-THP (Paclitaxel)]]<br>1h. [[#ddEC-THP_.28Docetaxel.29|ddEC-THP (Docetaxel)]]<br>1i. [[#FAC-THP_.28Paclitaxel.29|FAC-THP (Paclitaxel)]]<br>1j. [[#FAC-THP_.28Docetaxel.29|FAC-THP (Docetaxel)]]<br>1k. [[#FEC-THP_.28Paclitaxel.29|FEC-THP (Paclitaxel)]]<br>1l. [[#FEC-THP_.28Docetaxel.29|FEC-THP (Docetaxel)]]<br>1m. [[#TCHP_.28Docetaxel.29_2|TCHP (Docetaxel)]] |
+ | | style="background-color:#d73027" |Inferior IDFS<sup>1</sup> | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, FAC portion==== | + | ''Note that ranges for FAC are given in the protocol, replicated here.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, FAC portion (cycles 1 to 3)==== | ||
*[[Fluorouracil (5-FU)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Fluorouracil (5-FU)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Chemotherapy, TH portion (cycles 4 to 7)==== | |
− | + | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | |
− | + | ====Targeted therapy, TH portion==== | |
− | ====Chemotherapy, TH portion==== | ||
− | *[[ | ||
− | |||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 4: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 5 to 21: 6 mg/kg IV once on day 1 |
− | + | '''21-day cycle for 21 cycles (FAC x 3; TH x 4)''' | |
− | '''21-day cycle for | + | </div></div> |
− | |||
===References=== | ===References=== | ||
− | # von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [ | + | # '''APHINITY:''' von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [https://doi.org/10.1056/NEJMoa1703643 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28581356/ PubMed] [https://clinicaltrials.gov/study/NCT01358877 NCT01358877] |
− | + | ##'''Update:''' Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. [https://doi.org/10.1200/jco.20.01204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33539215/ PubMed] | |
− | ==FAC - | + | ==FAC-TH (Docetaxel) {{#subobject:urrg11|Regimen=1}}== |
− | + | FAC-TH: '''<u>F</u>'''luorouracil, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axotere (Docetaxel) & '''<u>H</u>'''erceptin (Trastuzumab) | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #1 {{#subobject:btr4cy|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | FAC - | + | !style="width: 20%"|Study |
− | + | !style="width: 20%"|Dates of enrollment | |
− | ===Regimen {{#subobject: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | {| | + | !style="width: 20%"|Comparator |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | |[[Levels_of_Evidence#Evidence| | ||
− | | | ||
− | |[[Levels_of_Evidence# | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | |2011-2013 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#AC-THP_.28Paclitaxel.29|AC-THP (Paclitaxel)]]<br>1b. [[#AC-THP_.28Docetaxel.29_2|AC-THP (Docetaxel)]]<br>1c. [[#ddAC-THP_.28Paclitaxel.29_2|ddAC-THP (Paclitaxel)]]<br>1c. [[#ddAC-THP_.28Docetaxel.29|ddAC-THP (Docetaxel)]]<br>1e. [[#EC-THP_.28Paclitaxel.29|EC-THP (Paclitaxel)]]<br>1f. [[#EC-THP_.28Docetaxel.29|EC-THP (Docetaxel)]]<br>1g. [[#ddEC-THP_.28Paclitaxel.29|ddEC-THP (Paclitaxel)]]<br>1h. [[#ddEC-THP_.28Docetaxel.29|ddEC-THP (Docetaxel)]]<br>1i. [[#FAC-THP_.28Paclitaxel.29|FAC-THP (Paclitaxel)]]<br>1j. [[#FAC-THP_.28Docetaxel.29|FAC-THP (Docetaxel)]]<br>1k. [[#FEC-THP_.28Paclitaxel.29|FEC-THP (Paclitaxel)]]<br>1l. [[#FEC-THP_.28Docetaxel.29|FEC-THP (Docetaxel)]]<br>1m. [[#TCHP_.28Docetaxel.29_2|TCHP (Docetaxel)]] |
+ | | style="background-color:#d73027" |Inferior IDFS<sup>1</sup> | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, FAC portion==== | + | ''Note that ranges for FAC are given in the protocol, replicated here.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, FAC portion (cycles 1 to 3)==== | ||
*[[Fluorouracil (5-FU)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Fluorouracil (5-FU)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Chemotherapy, TH portion (cycles 4 to 7)==== | |
− | + | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 | |
− | + | ====Targeted therapy, TH portion==== | |
− | ====Chemotherapy, | + | *[[Trastuzumab (Herceptin)]] as follows: |
− | *[[ | + | **Cycle 4: 8 mg/kg IV once on day 1 |
− | + | **Cycles 5 to 21: 6 mg/kg IV once on day 1 | |
− | *[[Trastuzumab (Herceptin)]] as follows: | + | '''21-day cycle for 21 cycles (FAC x 3; TH x 4)''' |
− | **Cycle | + | </div></div><br> |
− | ** | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | + | ===Regimen variant #2 {{#subobject:5hjg32|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | + | !style="width: 20%"|Study | |
− | + | !style="width: 20%"|Dates of enrollment | |
− | '''21-day cycle for | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | + | !style="width: 20%"|Comparator | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | ===Regimen # | ||
− | {| | ||
− | | | ||
− | |[[Levels_of_Evidence#Evidence| | ||
− | | | ||
− | |[[Levels_of_Evidence# | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | |2011-2013 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#AC-THP_.28Paclitaxel.29|AC-THP (Paclitaxel)]]<br>1b. [[#AC-THP_.28Docetaxel.29_2|AC-THP (Docetaxel)]]<br>1c. [[#ddAC-THP_.28Paclitaxel.29_2|ddAC-THP (Paclitaxel)]]<br>1c. [[#ddAC-THP_.28Docetaxel.29|ddAC-THP (Docetaxel)]]<br>1e. [[#EC-THP_.28Paclitaxel.29|EC-THP (Paclitaxel)]]<br>1f. [[#EC-THP_.28Docetaxel.29|EC-THP (Docetaxel)]]<br>1g. [[#ddEC-THP_.28Paclitaxel.29|ddEC-THP (Paclitaxel)]]<br>1h. [[#ddEC-THP_.28Docetaxel.29|ddEC-THP (Docetaxel)]]<br>1i. [[#FAC-THP_.28Paclitaxel.29|FAC-THP (Paclitaxel)]]<br>1j. [[#FAC-THP_.28Docetaxel.29|FAC-THP (Docetaxel)]]<br>1k. [[#FEC-THP_.28Paclitaxel.29|FEC-THP (Paclitaxel)]]<br>1l. [[#FEC-THP_.28Docetaxel.29|FEC-THP (Docetaxel)]]<br>1m. [[#TCHP_.28Docetaxel.29_2|TCHP (Docetaxel)]] |
+ | | style="background-color:#d73027" |Inferior IDFS<sup>1</sup> | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, FAC portion==== | + | ''Note that ranges for FAC are given in the protocol, replicated here.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, FAC portion (cycles 1 to 3)==== | ||
*[[Fluorouracil (5-FU)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Fluorouracil (5-FU)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Chemotherapy, TH portion (cycles 4 to 6)==== | |
− | |||
− | |||
− | ====Chemotherapy, | ||
*[[Docetaxel (Taxotere)]] as follows: | *[[Docetaxel (Taxotere)]] as follows: | ||
− | **Cycles | + | **Cycle 4: 75 mg/m<sup>2</sup> IV once on day 1 |
+ | **Cycles 5 & 6: 100 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, TH portion==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 4: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 5 to 21: 6 mg/kg IV once on day 1 |
− | + | '''21-day cycle for 21 cycles (FAC x 3; TH x 3)''' | |
− | + | </div></div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #3 {{#subobject:breot2|Variant=1}}=== | |
− | '''21-day cycle for | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | + | !style="width: 20%"|Study | |
− | ===Regimen # | + | !style="width: 20%"|Dates of enrollment |
− | {| | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | | | + | !style="width: 20%"|Comparator |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | | | ||
− | |[[Levels_of_Evidence# | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | |2011-2013 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#AC-THP_.28Paclitaxel.29|AC-THP (Paclitaxel)]]<br>1b. [[#AC-THP_.28Docetaxel.29_2|AC-THP (Docetaxel)]]<br>1c. [[#ddAC-THP_.28Paclitaxel.29_2|ddAC-THP (Paclitaxel)]]<br>1c. [[#ddAC-THP_.28Docetaxel.29|ddAC-THP (Docetaxel)]]<br>1e. [[#EC-THP_.28Paclitaxel.29|EC-THP (Paclitaxel)]]<br>1f. [[#EC-THP_.28Docetaxel.29|EC-THP (Docetaxel)]]<br>1g. [[#ddEC-THP_.28Paclitaxel.29|ddEC-THP (Paclitaxel)]]<br>1h. [[#ddEC-THP_.28Docetaxel.29|ddEC-THP (Docetaxel)]]<br>1i. [[#FAC-THP_.28Paclitaxel.29|FAC-THP (Paclitaxel)]]<br>1j. [[#FAC-THP_.28Docetaxel.29|FAC-THP (Docetaxel)]]<br>1k. [[#FEC-THP_.28Paclitaxel.29|FEC-THP (Paclitaxel)]]<br>1l. [[#FEC-THP_.28Docetaxel.29|FEC-THP (Docetaxel)]]<br>1m. [[#TCHP_.28Docetaxel.29_2|TCHP (Docetaxel)]] |
+ | | style="background-color:#d73027" |Inferior IDFS<sup>1</sup> | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, FAC portion==== | + | ''Note that ranges for FAC are given in the protocol, replicated here.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, FAC portion (cycles 1 to 3)==== | ||
*[[Fluorouracil (5-FU)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Fluorouracil (5-FU)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Chemotherapy, TH portion (cycles 4 to 6)==== | |
− | + | *[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1 | |
− | + | ====Targeted therapy, TH portion==== | |
− | ====Chemotherapy, | + | *[[Trastuzumab (Herceptin)]] as follows: |
− | *[[Docetaxel (Taxotere)]] | + | **Cycle 4: 8 mg/kg IV once on day 1 |
− | + | **Cycles 5 to 21: 6 mg/kg IV once on day 1 | |
− | + | '''21-day cycle for 21 cycles (FAC x 3; TH x 3)''' | |
− | *[[Trastuzumab (Herceptin)]] as follows: | + | </div></div> |
− | **Cycle | + | ===References=== |
− | ** | + | # '''APHINITY:''' von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [https://doi.org/10.1056/NEJMoa1703643 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28581356/ PubMed] [https://clinicaltrials.gov/study/NCT01358877 NCT01358877] |
− | + | ##'''Update:''' Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. [https://doi.org/10.1200/jco.20.01204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33539215/ PubMed] | |
− | + | ==FAC-THP (Paclitaxel) {{#subobject:u85g11|Regimen=1}}== | |
− | + | FAC-THP: '''<u>F</u>'''luorouracil, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axol (Paclitaxel), '''<u>H</u>'''erceptin (Trastuzumab), '''<u>P</u>'''ertuzumab | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | ''' | + | ===Regimen {{#subobject:9uh3rg|Variant=1}}=== |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | ===Regimen | + | !style="width: 20%"|Study |
− | {| | + | !style="width: 20%"|Dates of enrollment |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Comparator |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | |[[Levels_of_Evidence# | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" |
− | |[[# | + | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-133-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' |
− | |style="background-color:# | + | |- |
+ | |} --> | ||
+ | |2011-2013 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |1a. [[#AC-TH_.28Paclitaxel.29_2|AC-TH (Paclitaxel)]]<br>1b. [[#AC-TH_.28Docetaxel.29|AC-TH (Docetaxel)]]<br>1c. [[#ddAC-TH_.28Paclitaxel.29|ddAC-TH (Paclitaxel)]]<br>1d. [[#ddAC-TH_.28Docetaxel.29|ddAC-TH (Docetaxel)]]<br>1e. [[#EC-TH_.28Paclitaxel.29|EC-TH (Paclitaxel)]]<br>1f. [[#EC-TH_.28Docetaxel.29_2|EC-TH (Docetaxel)]]<br>1g. [[#ddEC-TH_.28Paclitaxel.29|ddEC-TH (Paclitaxel)]]<br>1h. [[#ddEC-TH_.28Docetaxel.29|ddEC-TH (Docetaxel)]]<br>1i. [[#FAC-TH_.28Paclitaxel.29|FAC-TH (Paclitaxel)]]<br>1j. [[#FAC-TH_.28Docetaxel.29|FAC-TH (Docetaxel)]]<br>1k. [[#FEC-TH_.28Paclitaxel.29_2|FEC-TH (Paclitaxel)]]<br>1l. [[#FEC-TH_.28Docetaxel.29|FEC-TH (Docetaxel)]]<br>1m. [[#TCH_.28Docetaxel.29|TCH (Taxotere)]] | ||
+ | | style="background-color:#1a9850" |Superior IDFS<sup>1</sup> (primary endpoint)<br>IDFS72: 91% vs 88%<br>(HR 0.76, 95% CI 0.64-0.91) | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, FAC portion==== | + | ''Note that ranges for FAC are given in the protocol, replicated here.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, FAC portion (cycles 1 to 3)==== | ||
*[[Fluorouracil (5-FU)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Fluorouracil (5-FU)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Chemotherapy, THP portion (cycles 4 to 7)==== | |
− | + | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | |
− | + | ====Targeted therapy, THP portion (cycles 4 to 21)==== | |
− | ====Chemotherapy, THP portion==== | ||
− | *[[ | ||
− | |||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 4: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 5 to 21: 6 mg/kg IV once on day 1 |
*[[Pertuzumab (Perjeta)]] as follows: | *[[Pertuzumab (Perjeta)]] as follows: | ||
− | **Cycle | + | **Cycle 4: 840 mg IV once on day 1 |
− | ** | + | **Cycles 5 to 21: 420 mg IV once on day 1 |
− | + | '''21-day cycle for 21 cycles (FAC x 3; THP x 4)''' | |
− | '''21-day cycle for | + | </div></div> |
− | |||
===References=== | ===References=== | ||
− | # von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [ | + | # '''APHINITY:''' von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [https://doi.org/10.1056/NEJMoa1703643 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28581356/ PubMed] [https://clinicaltrials.gov/study/NCT01358877 NCT01358877] |
− | + | ##'''Update:''' Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. [https://doi.org/10.1200/jco.20.01204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33539215/ PubMed] | |
− | == | + | ==FAC-THP (Docetaxel) {{#subobject:urr211|Regimen=1}}== |
− | {| class="wikitable" style=" | + | FAC-THP: '''<u>F</u>'''luorouracil, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axotere (Docetaxel), '''<u>H</u>'''erceptin (Trastuzumab), '''<u>P</u>'''ertuzumab |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1 {{#subobject:btrecy|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-133-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2011-2013 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |1a. [[#AC-TH_.28Paclitaxel.29_2|AC-TH (Paclitaxel)]]<br>1b. [[#AC-TH_.28Docetaxel.29|AC-TH (Docetaxel)]]<br>1c. [[#ddAC-TH_.28Paclitaxel.29|ddAC-TH (Paclitaxel)]]<br>1d. [[#ddAC-TH_.28Docetaxel.29|ddAC-TH (Docetaxel)]]<br>1e. [[#EC-TH_.28Paclitaxel.29|EC-TH (Paclitaxel)]]<br>1f. [[#EC-TH_.28Docetaxel.29_2|EC-TH (Docetaxel)]]<br>1g. [[#ddEC-TH_.28Paclitaxel.29|ddEC-TH (Paclitaxel)]]<br>1h. [[#ddEC-TH_.28Docetaxel.29|ddEC-TH (Docetaxel)]]<br>1i. [[#FAC-TH_.28Paclitaxel.29|FAC-TH (Paclitaxel)]]<br>1j. [[#FAC-TH_.28Docetaxel.29|FAC-TH (Docetaxel)]]<br>1k. [[#FEC-TH_.28Paclitaxel.29_2|FEC-TH (Paclitaxel)]]<br>1l. [[#FEC-TH_.28Docetaxel.29|FEC-TH (Docetaxel)]]<br>1m. [[#TCH_.28Docetaxel.29|TCH (Taxotere)]] | ||
+ | | style="background-color:#1a9850" |Superior IDFS<sup>1</sup> (primary endpoint)<br>IDFS72: 91% vs 88%<br>(HR 0.76, 95% CI 0.64-0.91) | ||
|- | |- | ||
− | |||
|} | |} | ||
− | ===Regimen {{#subobject: | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | {| | + | ''Note that ranges for FAC are given in the protocol, replicated here.'' |
− | | | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | |[[Levels_of_Evidence#Evidence| | + | ====Preceding treatment==== |
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, FAC portion (cycles 1 to 3)==== | ||
+ | *[[Fluorouracil (5-FU)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Chemotherapy, THP portion (cycles 4 to 7)==== | ||
+ | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, THP portion (cycles 4 to 21)==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 4: 8 mg/kg IV once on day 1 | ||
+ | **Cycles 5 to 21: 6 mg/kg IV once on day 1 | ||
+ | *[[Pertuzumab (Perjeta)]] as follows: | ||
+ | **Cycle 4: 840 mg IV once on day 1 | ||
+ | **Cycles 5 to 21: 420 mg IV once on day 1 | ||
+ | '''21-day cycle for 21 cycles (FAC x 3; THP x 4)''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2 {{#subobject:54jg32|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] |
− | |style="background-color:# | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" |
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-133-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' | ||
|- | |- | ||
− | |} | + | |} --> |
− | + | |2011-2013 | |
− | + | |style="background-color:#1a9851"|Phase 3 (E-esc) | |
− | + | |1a. [[#AC-TH_.28Paclitaxel.29_2|AC-TH (Paclitaxel)]]<br>1b. [[#AC-TH_.28Docetaxel.29|AC-TH (Docetaxel)]]<br>1c. [[#ddAC-TH_.28Paclitaxel.29|ddAC-TH (Paclitaxel)]]<br>1d. [[#ddAC-TH_.28Docetaxel.29|ddAC-TH (Docetaxel)]]<br>1e. [[#EC-TH_.28Paclitaxel.29|EC-TH (Paclitaxel)]]<br>1f. [[#EC-TH_.28Docetaxel.29_2|EC-TH (Docetaxel)]]<br>1g. [[#ddEC-TH_.28Paclitaxel.29|ddEC-TH (Paclitaxel)]]<br>1h. [[#ddEC-TH_.28Docetaxel.29|ddEC-TH (Docetaxel)]]<br>1i. [[#FAC-TH_.28Paclitaxel.29|FAC-TH (Paclitaxel)]]<br>1j. [[#FAC-TH_.28Docetaxel.29|FAC-TH (Docetaxel)]]<br>1k. [[#FEC-TH_.28Paclitaxel.29_2|FEC-TH (Paclitaxel)]]<br>1l. [[#FEC-TH_.28Docetaxel.29|FEC-TH (Docetaxel)]]<br>1m. [[#TCH_.28Docetaxel.29|TCH (Taxotere)]] | |
− | + | | style="background-color:#1a9850" |Superior IDFS<sup>1</sup> (primary endpoint)<br>IDFS72: 91% vs 88%<br>(HR 0.76, 95% CI 0.64-0.91) | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | # | ||
− | # | ||
− | |||
− | |||
− | |||
|- | |- | ||
− | |||
|} | |} | ||
− | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> | |
− | ===Regimen {{#subobject: | + | ''Note that ranges for FAC are given in the protocol, replicated here.'' |
− | {| | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | | | + | ====Preceding treatment==== |
− | |[[Levels_of_Evidence#Evidence| | + | *[[Surgery#Breast_cancer_surgery|Surgery]] |
− | | | + | </div> |
− | |[[Levels_of_Evidence# | + | <div class="toccolours" style="background-color:#b3e2cd"> |
+ | ====Chemotherapy, FAC portion (cycles 1 to 3)==== | ||
+ | *[[Fluorouracil (5-FU)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Chemotherapy, THP portion (cycles 4 to 6)==== | ||
+ | *[[Docetaxel (Taxotere)]] as follows: | ||
+ | **Cycle 4: 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | **Cycles 5 & 6: 100 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, THP portion (cycles 4 to 21)==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 4: 8 mg/kg IV once on day 1 | ||
+ | **Cycles 5 to 21: 6 mg/kg IV once on day 1 | ||
+ | *[[Pertuzumab (Perjeta)]] as follows: | ||
+ | **Cycle 4: 840 mg IV once on day 1 | ||
+ | **Cycles 5 to 21: 420 mg IV once on day 1 | ||
+ | '''21-day cycle for 21 cycles (FAC x 3; THP x 3)''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #3 {{#subobject:byeot2|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" |
− | |[[# | + | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-133-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' |
− | |style="background-color:# | + | |- |
+ | |} --> | ||
+ | |2011-2013 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |1a. [[#AC-TH_.28Paclitaxel.29_2|AC-TH (Paclitaxel)]]<br>1b. [[#AC-TH_.28Docetaxel.29|AC-TH (Docetaxel)]]<br>1c. [[#ddAC-TH_.28Paclitaxel.29|ddAC-TH (Paclitaxel)]]<br>1d. [[#ddAC-TH_.28Docetaxel.29|ddAC-TH (Docetaxel)]]<br>1e. [[#EC-TH_.28Paclitaxel.29|EC-TH (Paclitaxel)]]<br>1f. [[#EC-TH_.28Docetaxel.29_2|EC-TH (Docetaxel)]]<br>1g. [[#ddEC-TH_.28Paclitaxel.29|ddEC-TH (Paclitaxel)]]<br>1h. [[#ddEC-TH_.28Docetaxel.29|ddEC-TH (Docetaxel)]]<br>1i. [[#FAC-TH_.28Paclitaxel.29|FAC-TH (Paclitaxel)]]<br>1j. [[#FAC-TH_.28Docetaxel.29|FAC-TH (Docetaxel)]]<br>1k. [[#FEC-TH_.28Paclitaxel.29_2|FEC-TH (Paclitaxel)]]<br>1l. [[#FEC-TH_.28Docetaxel.29|FEC-TH (Docetaxel)]]<br>1m. [[#TCH_.28Docetaxel.29|TCH (Taxotere)]] | ||
+ | | style="background-color:#1a9850" |Superior IDFS<sup>1</sup> (primary endpoint)<br>IDFS72: 91% vs 88%<br>(HR 0.76, 95% CI 0.64-0.91) | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, | + | ''Note that ranges for FAC are given in the protocol, replicated here.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, FAC portion (cycles 1 to 3)==== | ||
*[[Fluorouracil (5-FU)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Fluorouracil (5-FU)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | *[[ | + | *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1 |
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Chemotherapy, THP portion (cycles 4 to 6)==== | |
− | + | *[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1 | |
− | + | ====Targeted therapy, THP portion (cycles 4 to 21)==== | |
− | ====Chemotherapy, | ||
− | *[[ | ||
− | |||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 4: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 5 to 21: 6 mg/kg IV once on day 1 |
− | + | *[[Pertuzumab (Perjeta)]] as follows: | |
− | '''21-day cycle for | + | **Cycle 4: 840 mg IV once on day 1 |
− | + | **Cycles 5 to 21: 420 mg IV once on day 1 | |
+ | '''21-day cycle for 21 cycles (FAC x 3; THP x 3)''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [ | + | # '''APHINITY:''' von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [https://doi.org/10.1056/NEJMoa1703643 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28581356/ PubMed] [https://clinicaltrials.gov/study/NCT01358877 NCT01358877] |
− | + | ##'''Update:''' Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. [https://doi.org/10.1200/jco.20.01204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33539215/ PubMed] | |
− | ==FEC -> | + | ==FEC-H {{#subobject:hi9g21|Regimen=1}}== |
− | {| class="wikitable" style=" | + | FEC-H: '''<u>F</u>'''luorouracil, '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide, followed by '''<u>H</u>'''erceptin (Trastuzumab) |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, FEC 75 {{#subobject:1CI332|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.20.00184 Sawaki et al. 2020 (RESPECT)] | ||
+ | |2009-10 to 2014-11 | ||
+ | | style="background-color:#1a9851" |Randomized (C) | ||
+ | |[[#Trastuzumab_monotherapy_2|Trastuzumab]] x 1 y | ||
+ | | style="background-color:#ffffbf" |Inconclusive whether non-inferior DFS (primary endpoint) | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | ''Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.'' | |
− | ===Regimen # | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | {| | + | ====Preceding treatment==== |
− | | | + | *[[Surgery#Breast_cancer_surgery|Surgery]] |
− | |[[Levels_of_Evidence#Evidence| | + | </div> |
− | | | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | |[[Levels_of_Evidence# | + | ====Chemotherapy, FEC portion (cycles 1 to 6)==== |
+ | *[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, H portion (cycles 7 to 24)==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 7: 8 mg/kg IV once on day 1 | ||
+ | **Cycles 8 to 24: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycle for 24 cycles (FEC x 6; H x 18)''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, FEC 100 x 4 {{#subobject:1kxkk2|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1200/jco.20.00184 Sawaki et al. 2020 (RESPECT)] |
− | |style="background-color:# | + | |2009-10 to 2014-11 |
− | + | | style="background-color:#1a9851" |Randomized (C) | |
− | |style="background-color:# | + | |[[#Trastuzumab_monotherapy_2|Trastuzumab]] x 1 y |
+ | | style="background-color:#ffffbf" |Inconclusive whether non-inferior DFS (primary endpoint) | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.'' |
− | ====Chemotherapy, FEC portion==== | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | *[[Fluorouracil (5-FU)]] 500 | + | ====Preceding treatment==== |
− | *[[Epirubicin (Ellence)]] | + | *[[Surgery#Breast_cancer_surgery|Surgery]] |
− | *[[Cyclophosphamide (Cytoxan)]] 500 | + | </div> |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | '''21-day cycle for 3 | + | ====Chemotherapy, FEC portion (cycles 1 to 4)==== |
− | + | *[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once on day 1 | |
− | ====Chemotherapy, | + | *[[Epirubicin (Ellence)]] 100 mg/m<sup>2</sup> IV once on day 1 |
− | *[[ | + | *[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1 |
− | ** | + | ====Targeted therapy, H portion (cycles 5 to 22)==== |
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 5: 8 mg/kg IV once on day 1 | ||
+ | **Cycles 6 to 22: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycle for 22 cycles (FEC x 4; H x 18)''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #3, FEC 100 x 6 {{#subobject:1Ccj23|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.20.00184 Sawaki et al. 2020 (RESPECT)] | ||
+ | |2009-10 to 2014-11 | ||
+ | | style="background-color:#1a9851" |Randomized (C) | ||
+ | |[[#Trastuzumab_monotherapy_2|Trastuzumab]] x 1 y | ||
+ | | style="background-color:#ffffbf" |Inconclusive whether non-inferior DFS (primary endpoint) | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, FEC portion (cycles 1 to 6)==== | ||
+ | *[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Epirubicin (Ellence)]] 100 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, H portion (cycles 7 to 24)==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 7: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 8 to 24: 6 mg/kg IV once on day 1 |
− | + | '''21-day cycle for 24 cycles (FEC x 6; H x 18)''' | |
− | '''21-day cycle for | + | </div></div> |
+ | ===References=== | ||
+ | # '''RESPECT:''' Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. [https://doi.org/10.1200/jco.20.00184 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/32936713/ PubMed] [https://clinicaltrials.gov/study/NCT01104935 NCT01104935] | ||
− | ===Regimen | + | ==FEC-TH (Paclitaxel) {{#subobject:hi9b11|Regimen=1}}== |
− | {| | + | FEC-TH: '''<u>F</u>'''luorouracil, '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axol (Paclitaxel) & '''<u>H</u>'''erceptin (Trastuzumab) |
− | | | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | |[[Levels_of_Evidence#Evidence| | + | ===Regimen {{#subobject:97uqqb|Variant=1}}=== |
− | | | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|Study |
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | |2011-2013 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#AC-THP_.28Paclitaxel.29|AC-THP (Paclitaxel)]]<br>1b. [[#AC-THP_.28Docetaxel.29_2|AC-THP (Docetaxel)]]<br>1c. [[#ddAC-THP_.28Paclitaxel.29_2|ddAC-THP (Paclitaxel)]]<br>1c. [[#ddAC-THP_.28Docetaxel.29|ddAC-THP (Docetaxel)]]<br>1e. [[#EC-THP_.28Paclitaxel.29|EC-THP (Paclitaxel)]]<br>1f. [[#EC-THP_.28Docetaxel.29|EC-THP (Docetaxel)]]<br>1g. [[#ddEC-THP_.28Paclitaxel.29|ddEC-THP (Paclitaxel)]]<br>1h. [[#ddEC-THP_.28Docetaxel.29|ddEC-THP (Docetaxel)]]<br>1i. [[#FAC-THP_.28Paclitaxel.29|FAC-THP (Paclitaxel)]]<br>1j. [[#FAC-THP_.28Docetaxel.29|FAC-THP (Docetaxel)]]<br>1k. [[#FEC-THP_.28Paclitaxel.29|FEC-THP (Paclitaxel)]]<br>1l. [[#FEC-THP_.28Docetaxel.29|FEC-THP (Docetaxel)]]<br>1m. [[#TCHP_.28Docetaxel.29_2|TCHP (Docetaxel)]] |
+ | | style="background-color:#d73027" |Inferior IDFS<sup>1</sup> | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, FEC portion==== | + | ''Note that ranges for FEC are given in the protocol, replicated here.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, FEC portion (cycles 1 to 3)==== | ||
*[[Fluorouracil (5-FU)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Fluorouracil (5-FU)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | *[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Chemotherapy, TH portion (cycles 4 to 7)==== | |
− | + | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | |
− | + | ====Targeted therapy, TH portion==== | |
− | ====Chemotherapy, TH portion==== | ||
− | *[[ | ||
− | |||
− | |||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 4: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 5 to 21: 6 mg/kg IV once on day 1 |
+ | '''21-day cycle for 21 cycles (FEC x 3; TH x 4)''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''APHINITY:''' von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [https://doi.org/10.1056/NEJMoa1703643 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28581356/ PubMed] [https://clinicaltrials.gov/study/NCT01358877 NCT01358877] | ||
+ | ##'''Update:''' Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. [https://doi.org/10.1200/jco.20.01204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33539215/ PubMed] | ||
− | ''' | + | ==FEC-TH (Docetaxel) {{#subobject:hi9c77|Regimen=1}}== |
− | + | FEC-TH: '''<u>F</u>'''luorouracil, '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axotere (Docetaxel) & '''<u>H</u>'''erceptin (Trastuzumab) | |
− | ===Regimen # | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| | + | ===Regimen variant #1 {{#subobject:btrx67|Variant=1}}=== |
− | | | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Study |
− | | | + | !style="width: 20%"|Dates of enrollment |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | |2011-2013 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#AC-THP_.28Paclitaxel.29|AC-THP (Paclitaxel)]]<br>1b. [[#AC-THP_.28Docetaxel.29_2|AC-THP (Docetaxel)]]<br>1c. [[#ddAC-THP_.28Paclitaxel.29_2|ddAC-THP (Paclitaxel)]]<br>1c. [[#ddAC-THP_.28Docetaxel.29|ddAC-THP (Docetaxel)]]<br>1e. [[#EC-THP_.28Paclitaxel.29|EC-THP (Paclitaxel)]]<br>1f. [[#EC-THP_.28Docetaxel.29|EC-THP (Docetaxel)]]<br>1g. [[#ddEC-THP_.28Paclitaxel.29|ddEC-THP (Paclitaxel)]]<br>1h. [[#ddEC-THP_.28Docetaxel.29|ddEC-THP (Docetaxel)]]<br>1i. [[#FAC-THP_.28Paclitaxel.29|FAC-THP (Paclitaxel)]]<br>1j. [[#FAC-THP_.28Docetaxel.29|FAC-THP (Docetaxel)]]<br>1k. [[#FEC-THP_.28Paclitaxel.29|FEC-THP (Paclitaxel)]]<br>1l. [[#FEC-THP_.28Docetaxel.29|FEC-THP (Docetaxel)]]<br>1m. [[#TCHP_.28Docetaxel.29_2|TCHP (Docetaxel)]] |
+ | | style="background-color:#d73027" |Inferior IDFS<sup>1</sup> | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, FEC portion==== | + | ''Note that ranges for FEC are given in the protocol, replicated here.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, FEC portion (cycles 1 to 3)==== | ||
*[[Fluorouracil (5-FU)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Fluorouracil (5-FU)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | *[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Chemotherapy, TH portion (cycles 4 to 7)==== | |
− | + | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 | |
− | + | ====Targeted therapy, TH portion==== | |
− | ====Chemotherapy, TH portion==== | ||
− | *[[Docetaxel (Taxotere)]] | ||
− | |||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 4: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 5 to 21: 6 mg/kg IV once on day 1 |
− | + | '''21-day cycle for 21 cycles (FEC x 3; TH x 4)''' | |
− | '''21-day cycle for | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #2 {{#subobject:5hkk92|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | + | !style="width: 20%"|Study | |
− | + | !style="width: 20%"|Dates of enrollment | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
− | + | !style="width: 20%"|Comparator | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | |
− | |||
− | |||
− | |||
− | ===Regimen {{#subobject: | ||
− | {| | ||
− | | | ||
− | |[[Levels_of_Evidence#Evidence| | ||
− | | | ||
− | |[[Levels_of_Evidence# | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | |2011-2013 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#AC-THP_.28Paclitaxel.29|AC-THP (Paclitaxel)]]<br>1b. [[#AC-THP_.28Docetaxel.29_2|AC-THP (Docetaxel)]]<br>1c. [[#ddAC-THP_.28Paclitaxel.29_2|ddAC-THP (Paclitaxel)]]<br>1c. [[#ddAC-THP_.28Docetaxel.29|ddAC-THP (Docetaxel)]]<br>1e. [[#EC-THP_.28Paclitaxel.29|EC-THP (Paclitaxel)]]<br>1f. [[#EC-THP_.28Docetaxel.29|EC-THP (Docetaxel)]]<br>1g. [[#ddEC-THP_.28Paclitaxel.29|ddEC-THP (Paclitaxel)]]<br>1h. [[#ddEC-THP_.28Docetaxel.29|ddEC-THP (Docetaxel)]]<br>1i. [[#FAC-THP_.28Paclitaxel.29|FAC-THP (Paclitaxel)]]<br>1j. [[#FAC-THP_.28Docetaxel.29|FAC-THP (Docetaxel)]]<br>1k. [[#FEC-THP_.28Paclitaxel.29|FEC-THP (Paclitaxel)]]<br>1l. [[#FEC-THP_.28Docetaxel.29|FEC-THP (Docetaxel)]]<br>1m. [[#TCHP_.28Docetaxel.29_2|TCHP (Docetaxel)]] |
+ | | style="background-color:#d73027" |Inferior IDFS<sup>1</sup> | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, FEC portion==== | + | ''Note that ranges for FEC are given in the protocol, replicated here.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, FEC portion (cycles 1 to 3)==== | ||
*[[Fluorouracil (5-FU)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Fluorouracil (5-FU)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | *[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Chemotherapy, TH portion (cycles 4 to 6)==== | |
− | + | *[[Docetaxel (Taxotere)]] as follows: | |
− | + | **Cycle 4: 75 mg/m<sup>2</sup> IV once on day 1 | |
− | ====Chemotherapy, | + | **Cycles 5 & 6: 100 mg/m<sup>2</sup> IV once on day 1 |
− | *[[ | + | ====Targeted therapy, TH portion==== |
− | ** | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 4: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 5 to 21: 6 mg/kg IV once on day 1 |
− | + | '''21-day cycle for 21 cycles (FEC x 3; TH x 3)''' | |
− | + | </div></div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #3 {{#subobject:greot2|Variant=1}}=== | |
− | '''21-day cycle for | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | + | !style="width: 20%"|Study | |
− | + | !style="width: 20%"|Dates of enrollment | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
− | + | !style="width: 20%"|Comparator | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | ===Regimen # | ||
− | {| | ||
− | | | ||
− | |[[Levels_of_Evidence#Evidence| | ||
− | | | ||
− | |[[Levels_of_Evidence# | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | |2011-2013 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#AC-THP_.28Paclitaxel.29|AC-THP (Paclitaxel)]]<br>1b. [[#AC-THP_.28Docetaxel.29_2|AC-THP (Docetaxel)]]<br>1c. [[#ddAC-THP_.28Paclitaxel.29_2|ddAC-THP (Paclitaxel)]]<br>1c. [[#ddAC-THP_.28Docetaxel.29|ddAC-THP (Docetaxel)]]<br>1e. [[#EC-THP_.28Paclitaxel.29|EC-THP (Paclitaxel)]]<br>1f. [[#EC-THP_.28Docetaxel.29|EC-THP (Docetaxel)]]<br>1g. [[#ddEC-THP_.28Paclitaxel.29|ddEC-THP (Paclitaxel)]]<br>1h. [[#ddEC-THP_.28Docetaxel.29|ddEC-THP (Docetaxel)]]<br>1i. [[#FAC-THP_.28Paclitaxel.29|FAC-THP (Paclitaxel)]]<br>1j. [[#FAC-THP_.28Docetaxel.29|FAC-THP (Docetaxel)]]<br>1k. [[#FEC-THP_.28Paclitaxel.29|FEC-THP (Paclitaxel)]]<br>1l. [[#FEC-THP_.28Docetaxel.29|FEC-THP (Docetaxel)]]<br>1m. [[#TCHP_.28Docetaxel.29_2|TCHP (Docetaxel)]] |
+ | | style="background-color:#d73027" |Inferior IDFS<sup>1</sup> | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy, FEC portion==== | + | ''Note that ranges for FEC are given in the protocol, replicated here.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, FEC portion (cycles 1 to 3)==== | ||
*[[Fluorouracil (5-FU)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Fluorouracil (5-FU)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | *[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Chemotherapy, TH portion (cycles 4 to 6)==== | |
− | '''21-day cycle for 3 | + | *[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1 |
− | + | ====Targeted therapy, TH portion==== | |
− | ====Chemotherapy, | + | *[[Trastuzumab (Herceptin)]] as follows: |
+ | **Cycle 4: 8 mg/kg IV once on day 1 | ||
+ | **Cycles 5 to 21: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycle for 21 cycles (FEC x 3; TH x 3)''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''APHINITY:''' von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [https://doi.org/10.1056/NEJMoa1703643 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28581356/ PubMed] [https://clinicaltrials.gov/study/NCT01358877 NCT01358877] | ||
+ | ##'''Update:''' Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. [https://doi.org/10.1200/jco.20.01204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33539215/ PubMed] | ||
+ | ==ddFEC-ddTH (Docetaxel) {{#subobject:45dbc1|Regimen=1}}== | ||
+ | ddFEC-ddTH (Docetaxel): '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>F</u>'''luorouracil, '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide, followed by ddTH: '''<u>d</u>'''ose-'''<u>d</u>'''ense '''<u>T</u>'''axotere (Docetaxel) & '''<u>H</u>'''erceptin (Trastuzumab) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:21ab45|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1093/annonc/mdv213 Mavroudis et al. 2015 (HORG CT/04.23)] | ||
+ | |2004-2012 | ||
+ | | style="background-color:#91cf61" |Phase 3 (C) | ||
+ | |[[#ddFEC-ddTH_.28Docetaxel.29|ddFEC-ddTH]]; 6-months total of trastuzumab | ||
+ | | style="background-color:#ffffbf" |Inconclusive whether non-inferior DFS36 | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, ddFEC portion (cycles 1 to 4)==== | ||
+ | *[[Fluorouracil (5-FU)]] 700 mg/m<sup>2</sup> IV over 5 to 15 minutes once on day 1 | ||
+ | *[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV over 5 to 15 minutes once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 700 mg/m<sup>2</sup> IV over 30 to 60 minutes once on day 1 | ||
+ | ====Supportive therapy, ddFEC portion (cycles 1 to 4)==== | ||
+ | *[[Filgrastim (Neupogen)]] 5 mcg/kg (rounded to 300 or 480 mcg) SC once per day on days 3 to 10 | ||
+ | ====Chemotherapy, ddTH portion (cycles 5 to 20)==== | ||
*[[Docetaxel (Taxotere)]] as follows: | *[[Docetaxel (Taxotere)]] as follows: | ||
− | **Cycles | + | **Cycles 5 to 8: 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1 |
+ | ====Targeted therapy, ddTH portion (cycles 5 to 20)==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle 1: | + | **Cycle 5: 6 mg/kg IV once on day 1 |
− | ** | + | **Cycles 6 to 8: 4 mg/kg IV once on day 1 |
− | *[[ | + | **Cycles 9 to 20: 6 mg/kg IV once on day 1 |
− | ** | + | ====Supportive therapy, ddTH portion (cycles 5 to 20)==== |
− | + | *[[Filgrastim (Neupogen)]] as follows: | |
− | + | **Cycles 5 to 8: 5 mcg/kg (rounded to 300 or 480 mcg) SC once per day on days 3 to 10 | |
− | '''21-day cycle for | + | '''14-day cycle for 8 cycles, then 21-day cycle for 12 cycles (1 year total)''' |
− | + | </div></div> | |
− | === | + | ===References=== |
− | {| | + | # '''HORG CT/04.23:''' Mavroudis D, Saloustros E, Malamos N, Kakolyris S, Boukovinas I, Papakotoulas P, Kentepozidis N, Ziras N, Georgoulias V; Hellenic Oncology Research Group. Six versus 12 months of adjuvant trastuzumab in combination with dose-dense chemotherapy for women with HER2-positive breast cancer: a multicenter randomized study by the Hellenic Oncology Research Group (HORG). Ann Oncol. 2015 Jul;26(7):1333-40. Epub 2015 May 1. [https://doi.org/10.1093/annonc/mdv213 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25935793/ PubMed] [https://clinicaltrials.gov/study/NCT00615602 NCT00615602] |
− | | | + | ==FEC-THP (Paclitaxel) {{#subobject:hi9b21|Regimen=1}}== |
− | |[[Levels_of_Evidence#Evidence| | + | FEC-THP: '''<u>F</u>'''luorouracil, '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axol (Paclitaxel), '''<u>H</u>'''erceptin (Trastuzumab), '''<u>P</u>'''ertuzumab |
− | | | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | |[[Levels_of_Evidence# | + | ===Protocol {{#subobject:97u4qb|Variant=1}}=== |
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" |
− | |[[# | + | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-133-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' |
− | |style="background-color:# | + | |- |
+ | |} --> | ||
+ | |2011-2013 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |1a. [[#AC-TH_.28Paclitaxel.29_2|AC-TH (Paclitaxel)]]<br>1b. [[#AC-TH_.28Docetaxel.29|AC-TH (Docetaxel)]]<br>1c. [[#ddAC-TH_.28Paclitaxel.29|ddAC-TH (Paclitaxel)]]<br>1d. [[#ddAC-TH_.28Docetaxel.29|ddAC-TH (Docetaxel)]]<br>1e. [[#EC-TH_.28Paclitaxel.29|EC-TH (Paclitaxel)]]<br>1f. [[#EC-TH_.28Docetaxel.29_2|EC-TH (Docetaxel)]]<br>1g. [[#ddEC-TH_.28Paclitaxel.29|ddEC-TH (Paclitaxel)]]<br>1h. [[#ddEC-TH_.28Docetaxel.29|ddEC-TH (Docetaxel)]]<br>1i. [[#FAC-TH_.28Paclitaxel.29|FAC-TH (Paclitaxel)]]<br>1j. [[#FAC-TH_.28Docetaxel.29|FAC-TH (Docetaxel)]]<br>1k. [[#FEC-TH_.28Paclitaxel.29_2|FEC-TH (Paclitaxel)]]<br>1l. [[#FEC-TH_.28Docetaxel.29|FEC-TH (Docetaxel)]]<br>1m. [[#TCH_.28Docetaxel.29|TCH (Taxotere)]] | ||
+ | | style="background-color:#1a9850" |Superior IDFS<sup>1</sup> (primary endpoint)<br>IDFS72: 91% vs 88%<br>(HR 0.76, 95% CI 0.64-0.91) | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ Krop et al. 2021 (KAITLIN)] | ||
+ | |2014-01 to 2015-06 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#AC-KP_999|AC-KP]]<br>1b. [[#ddAC-KP_999|ddAC-KP]]<br>1c. [[#EC-KP_999|EC-KP]]<br>1d. [[#ddEC-KP|ddEC-KP]]<br>1e. [[#FEC-KP|FEC-KP]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of IDFS | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
+ | ''Note that ranges for FEC dosing and number of cycles are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m<sup>2</sup> of epirubicin per cycle.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy, FEC portion==== | ====Chemotherapy, FEC portion==== | ||
*[[Fluorouracil (5-FU)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Fluorouracil (5-FU)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | *[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | '''21-day cycle for 3 to 4 cycles''' | |
− | '''21-day cycle for 3 cycles | ||
− | |||
====Chemotherapy, THP portion==== | ====Chemotherapy, THP portion==== | ||
− | *[[ | + | *[[Paclitaxel (Taxol)]] as follows: |
− | ** | + | **Cycles 1 to 4: 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 |
− | + | ====Targeted therapy, THP portion==== | |
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
**Cycle 1: 8 mg/kg IV once on day 1 | **Cycle 1: 8 mg/kg IV once on day 1 | ||
− | ** | + | **Cycles 2 to 18: 6 mg/kg IV once on day 1 |
*[[Pertuzumab (Perjeta)]] as follows: | *[[Pertuzumab (Perjeta)]] as follows: | ||
**Cycle 1: 840 mg IV once on day 1 | **Cycle 1: 840 mg IV once on day 1 | ||
− | ** | + | **Cycles 2 to 18: 420 mg IV once on day 1 |
− | + | '''21-day cycle for 18 cycles (1 year)''' | |
− | '''21-day cycle for | + | </div></div> |
− | + | ===References=== | |
− | === | + | # '''APHINITY:''' von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [https://doi.org/10.1056/NEJMoa1703643 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28581356/ PubMed] [https://clinicaltrials.gov/study/NCT01358877 NCT01358877] |
− | {| | + | ##'''Update:''' Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. [https://doi.org/10.1200/jco.20.01204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33539215/ PubMed] |
− | | | + | #'''KAITLIN:''' Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. [https://doi.org/10.1200/jco.21.00896 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34890214/ PubMed] [https://clinicaltrials.gov/study/NCT01966471 NCT01966471] |
− | |[[Levels_of_Evidence#Evidence| | + | ==FEC-THP (Docetaxel) {{#subobject:hi3c77|Regimen=1}}== |
− | | | + | FEC-THP: '''<u>F</u>'''luorouracil, '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide, followed by '''<u>T</u>'''axotere (Docetaxel), '''<u>H</u>'''erceptin (Trastuzumab), '''<u>P</u>'''ertuzumab |
− | |[[Levels_of_Evidence# | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Protocol variant #1 {{#subobject:btrx07|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
− | |style="background-color:# | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" |
− | |[[# | + | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-133-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' |
− | |style="background-color:# | + | |- |
+ | |} --> | ||
+ | |2011-2013 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |1a. [[#AC-TH_.28Paclitaxel.29_2|AC-TH (Paclitaxel)]]<br>1b. [[#AC-TH_.28Docetaxel.29|AC-TH (Docetaxel)]]<br>1c. [[#ddAC-TH_.28Paclitaxel.29|ddAC-TH (Paclitaxel)]]<br>1d. [[#ddAC-TH_.28Docetaxel.29|ddAC-TH (Docetaxel)]]<br>1e. [[#EC-TH_.28Paclitaxel.29|EC-TH (Paclitaxel)]]<br>1f. [[#EC-TH_.28Docetaxel.29_2|EC-TH (Docetaxel)]]<br>1g. [[#ddEC-TH_.28Paclitaxel.29|ddEC-TH (Paclitaxel)]]<br>1h. [[#ddEC-TH_.28Docetaxel.29|ddEC-TH (Docetaxel)]]<br>1i. [[#FAC-TH_.28Paclitaxel.29|FAC-TH (Paclitaxel)]]<br>1j. [[#FAC-TH_.28Docetaxel.29|FAC-TH (Docetaxel)]]<br>1k. [[#FEC-TH_.28Paclitaxel.29_2|FEC-TH (Paclitaxel)]]<br>1l. [[#FEC-TH_.28Docetaxel.29|FEC-TH (Docetaxel)]]<br>1m. [[#TCH_.28Docetaxel.29|TCH (Taxotere)]] | ||
+ | | style="background-color:#1a9850" |Superior IDFS<sup>1</sup> (primary endpoint)<br>IDFS72: 91% vs 88%<br>(HR 0.76, 95% CI 0.64-0.91) | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ Krop et al. 2021 (KAITLIN)] | ||
+ | |2014-01 to 2015-06 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#AC-KP_999|AC-KP]]<br>1b. [[#ddAC-KP_999|ddAC-KP]]<br>1c. [[#EC-KP_999|EC-KP]]<br>1d. [[#ddEC-KP|ddEC-KP]]<br>1e. [[#FEC-KP|FEC-KP]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of IDFS | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
+ | ''Note that ranges for FEC dosing and number of cycles are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m<sup>2</sup> of epirubicin per cycle.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy, FEC portion==== | ====Chemotherapy, FEC portion==== | ||
*[[Fluorouracil (5-FU)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Fluorouracil (5-FU)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | *[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | '''21-day cycle for 3 to 4 cycles''' | |
− | '''21-day cycle for 3 cycles | ||
− | |||
====Chemotherapy, THP portion==== | ====Chemotherapy, THP portion==== | ||
*[[Docetaxel (Taxotere)]] as follows: | *[[Docetaxel (Taxotere)]] as follows: | ||
**Cycles 1 to 4: 75 mg/m<sup>2</sup> IV once on day 1 | **Cycles 1 to 4: 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, THP portion==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
**Cycle 1: 8 mg/kg IV once on day 1 | **Cycle 1: 8 mg/kg IV once on day 1 | ||
− | ** | + | **Cycles 2 to 18: 6 mg/kg IV once on day 1 |
*[[Pertuzumab (Perjeta)]] as follows: | *[[Pertuzumab (Perjeta)]] as follows: | ||
**Cycle 1: 840 mg IV once on day 1 | **Cycle 1: 840 mg IV once on day 1 | ||
− | ** | + | **Cycles 2 to 18: 420 mg IV once on day 1 |
− | + | '''21-day cycle for 18 cycles (1 year)''' | |
− | '''21-day cycle for | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | == | + | ===Protocol variant #2 {{#subobject:5hrk92|Variant=1}}=== |
− | # | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | + | !style="width: 20%"|Study | |
− | + | !style="width: 20%"|Dates of enrollment | |
− | {| class="wikitable" style=" | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] |
− | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | |
− | + | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-133-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | | | ||
− | |||
− | |||
− | | | ||
− | |||
− | ' | ||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
|- | |- | ||
− | | | + | |} --> |
− | | | + | |2011-2013 |
− | + | |style="background-color:#1a9851"|Phase 3 (E-esc) | |
− | + | |1a. [[#AC-TH_.28Paclitaxel.29_2|AC-TH (Paclitaxel)]]<br>1b. [[#AC-TH_.28Docetaxel.29|AC-TH (Docetaxel)]]<br>1c. [[#ddAC-TH_.28Paclitaxel.29|ddAC-TH (Paclitaxel)]]<br>1d. [[#ddAC-TH_.28Docetaxel.29|ddAC-TH (Docetaxel)]]<br>1e. [[#EC-TH_.28Paclitaxel.29|EC-TH (Paclitaxel)]]<br>1f. [[#EC-TH_.28Docetaxel.29_2|EC-TH (Docetaxel)]]<br>1g. [[#ddEC-TH_.28Paclitaxel.29|ddEC-TH (Paclitaxel)]]<br>1h. [[#ddEC-TH_.28Docetaxel.29|ddEC-TH (Docetaxel)]]<br>1i. [[#FAC-TH_.28Paclitaxel.29|FAC-TH (Paclitaxel)]]<br>1j. [[#FAC-TH_.28Docetaxel.29|FAC-TH (Docetaxel)]]<br>1k. [[#FEC-TH_.28Paclitaxel.29_2|FEC-TH (Paclitaxel)]]<br>1l. [[#FEC-TH_.28Docetaxel.29|FEC-TH (Docetaxel)]]<br>1m. [[#TCH_.28Docetaxel.29|TCH (Taxotere)]] | |
− | | | + | | style="background-color:#1a9850" |Superior IDFS<sup>1</sup> (primary endpoint)<br>IDFS72: 91% vs 88%<br>(HR 0.76, 95% CI 0.64-0.91) |
− | |[[ | ||
− | | | ||
− | |[[ | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ Krop et al. 2021 (KAITLIN)] |
− | |style="background-color:# | + | |2014-01 to 2015-06 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#AC-KP_999|AC-KP]]<br>1b. [[#ddAC-KP_999|ddAC-KP]]<br>1c. [[#EC-KP_999|EC-KP]]<br>1d. [[#ddEC-KP|ddEC-KP]]<br>1e. [[#FEC-KP|FEC-KP]] |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of IDFS | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | + | ''Note that ranges for FEC dosing and number of cycles are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m<sup>2</sup> of epirubicin per cycle.'' | |
− | === | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | # | + | ====Preceding treatment==== |
− | + | *[[Surgery#Breast_cancer_surgery|Surgery]] | |
− | == | + | </div> |
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#b3e2cd"> |
+ | ====Chemotherapy, FEC portion==== | ||
+ | *[[Fluorouracil (5-FU)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | '''21-day cycle for 3 to 4 cycles''' | ||
+ | ====Chemotherapy, THP portion==== | ||
+ | *[[Docetaxel (Taxotere)]] as follows: | ||
+ | **Cycle 1: 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | **Cycles 2 & 3: 100 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, THP portion==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycles 2 to 18: 6 mg/kg IV once on day 1 | ||
+ | *[[Pertuzumab (Perjeta)]] as follows: | ||
+ | **Cycle 1: 840 mg IV once on day 1 | ||
+ | **Cycles 2 to 18: 420 mg IV once on day 1 | ||
+ | '''21-day cycle for 18 cycles (1 year)''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Protocol variant #3 {{#subobject:grqot2|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-133-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' | ||
|- | |- | ||
− | |[[# | + | |} --> |
− | | | + | |2011-2013 |
− | + | |style="background-color:#1a9851"|Phase 3 (E-esc) | |
− | + | |1a. [[#AC-TH_.28Paclitaxel.29_2|AC-TH (Paclitaxel)]]<br>1b. [[#AC-TH_.28Docetaxel.29|AC-TH (Docetaxel)]]<br>1c. [[#ddAC-TH_.28Paclitaxel.29|ddAC-TH (Paclitaxel)]]<br>1d. [[#ddAC-TH_.28Docetaxel.29|ddAC-TH (Docetaxel)]]<br>1e. [[#EC-TH_.28Paclitaxel.29|EC-TH (Paclitaxel)]]<br>1f. [[#EC-TH_.28Docetaxel.29_2|EC-TH (Docetaxel)]]<br>1g. [[#ddEC-TH_.28Paclitaxel.29|ddEC-TH (Paclitaxel)]]<br>1h. [[#ddEC-TH_.28Docetaxel.29|ddEC-TH (Docetaxel)]]<br>1i. [[#FAC-TH_.28Paclitaxel.29|FAC-TH (Paclitaxel)]]<br>1j. [[#FAC-TH_.28Docetaxel.29|FAC-TH (Docetaxel)]]<br>1k. [[#FEC-TH_.28Paclitaxel.29_2|FEC-TH (Paclitaxel)]]<br>1l. [[#FEC-TH_.28Docetaxel.29|FEC-TH (Docetaxel)]]<br>1m. [[#TCH_.28Docetaxel.29|TCH (Taxotere)]] | |
− | + | | style="background-color:#1a9850" |Superior IDFS<sup>1</sup> (primary endpoint)<br>IDFS72: 91% vs 88%<br>(HR 0.76, 95% CI 0.64-0.91) | |
− | |||
− | |||
− | |||
− | |||
|- | |- | ||
− | |[https://www.ncbi.nlm.nih.gov/pmc/articles/ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ Krop et al. 2021 (KAITLIN)] |
− | |style="background-color:# | + | |2014-01 to 2015-06 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#AC-KP_999|AC-KP]]<br>1b. [[#ddAC-KP_999|ddAC-KP]]<br>1c. [[#EC-KP_999|EC-KP]]<br>1d. [[#ddEC-KP|ddEC-KP]]<br>1e. [[#FEC-KP|FEC-KP]] |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of IDFS | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for APHINITY is based on the 2021 update.''<br> |
− | ====Chemotherapy==== | + | ''Note that ranges for FEC dosing and number of cycles are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m<sup>2</sup> of epirubicin per cycle.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, FEC portion==== | ||
+ | *[[Fluorouracil (5-FU)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Epirubicin (Ellence)]] 90 to 120 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 500 to 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | '''21-day cycle for 3 to 4 cycles''' | ||
+ | ====Chemotherapy, THP portion==== | ||
*[[Docetaxel (Taxotere)]] as follows: | *[[Docetaxel (Taxotere)]] as follows: | ||
− | **Cycles 1 to | + | **Cycles 1 to 3: 100 mg/m<sup>2</sup> IV once on day 1 |
− | + | ====Targeted therapy, THP portion==== | |
− | |||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
**Cycle 1: 8 mg/kg IV once on day 1 | **Cycle 1: 8 mg/kg IV once on day 1 | ||
− | ** | + | **Cycles 2 to 18: 6 mg/kg IV once on day 1 |
− | + | *[[Pertuzumab (Perjeta)]] as follows: | |
− | '''21-day cycle for | + | **Cycle 1: 840 mg IV once on day 1 |
− | + | **Cycles 2 to 18: 420 mg IV once on day 1 | |
− | ===Regimen | + | '''21-day cycle for 18 cycles (1 year)''' |
− | {| | + | </div></div> |
− | | | + | ===References=== |
− | |[[Levels_of_Evidence#Evidence| | + | # '''APHINITY:''' von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [https://doi.org/10.1056/NEJMoa1703643 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28581356/ PubMed] [https://clinicaltrials.gov/study/NCT01358877 NCT01358877] |
− | | | + | ##'''Update:''' Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. [https://doi.org/10.1200/jco.20.01204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33539215/ PubMed] |
− | |[[Levels_of_Evidence# | + | #'''KAITLIN:''' Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. [https://doi.org/10.1200/jco.21.00896 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824393/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34890214/ PubMed] [https://clinicaltrials.gov/study/NCT01966471 NCT01966471] |
+ | ==T-H (Docetaxel) {{#subobject:1tjgi3|Regimen=1}}== | ||
+ | T-H: '''<u>T</u>'''axotere (Docetaxel) followed by '''<u>H</u>'''erceptin (Trastuzumab) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:jv353c|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | + | |[https://doi.org/10.1200/jco.20.00184 Sawaki et al. 2020 (RESPECT)] | |
− | | | + | |2009-10 to 2014-11 |
− | |[[ | + | | style="background-color:#1a9851" |Randomized (C) |
− | |style="background-color:# | + | |[[#Trastuzumab_monotherapy_2|Trastuzumab]] x 1 y |
+ | | style="background-color:#ffffbf" |Inconclusive whether non-inferior DFS (primary endpoint) | ||
|- | |- | ||
− | |[[# | + | |} |
− | |style="background-color:# | + | ''Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, T portion (cycles 1 to 4)==== | ||
+ | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, H portion (cycles 5 to 22)==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 5: 8 mg/kg IV once on day 1 | ||
+ | **Cycles 6 to 22: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycle for 22 cycles (T x 4; H x 18)''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''RESPECT:''' Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. [https://doi.org/10.1200/jco.20.00184 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/32936713/ PubMed] [https://clinicaltrials.gov/study/NCT01104935 NCT01104935] | ||
+ | ==T-H (Paclitaxel) {{#subobject:ixcgi3|Regimen=1}}== | ||
+ | T-H: '''<u>T</u>'''axol (Paclitaxel) followed by '''<u>H</u>'''erceptin (Trastuzumab) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:cnk33c|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.20.00184 Sawaki et al. 2020 (RESPECT)] | ||
+ | |2009-10 to 2014-11 | ||
+ | | style="background-color:#1a9851" |Randomized (C) | ||
+ | |[[#Trastuzumab_monotherapy_2|Trastuzumab]] x 1 y | ||
+ | | style="background-color:#ffffbf" |Inconclusive whether non-inferior DFS (primary endpoint) | ||
|- | |- | ||
|} | |} | ||
− | ====Chemotherapy==== | + | ''Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.'' |
− | *[[ | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | + | ====Preceding treatment==== | |
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, T portion (cycles 1 to 12)==== | ||
+ | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, H portion (cycles 13 to 30)==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle | + | **Cycle 13: 8 mg/kg IV once on day 1 |
− | **Cycles | + | **Cycles 14 to 30: 6 mg/kg IV once on day 1 |
− | + | '''7-day cycle for 12 cycles, then 21-day cycle for 18 cycles (T x 12; H x 18)''' | |
− | ''' | + | </div></div> |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
===References=== | ===References=== | ||
− | + | # '''RESPECT:''' Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. [https://doi.org/10.1200/jco.20.00184 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/32936713/ PubMed] [https://clinicaltrials.gov/study/NCT01104935 NCT01104935] | |
− | # | + | ==TC-H (Docetaxel) {{#subobject:1t621b|Regimen=1}}== |
− | + | TC-H: '''<u>T</u>'''axotere (Docetaxel) & '''<u>C</u>'''yclophosphamide, followed by '''<u>H</u>'''erceptin (Trastuzumab) | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | == | + | ===Regimen {{#subobject:1igj3c|Variant=1}}=== |
− | {| class="wikitable" style=" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.20.00184 Sawaki et al. 2020 (RESPECT)] | ||
+ | |2009-10 to 2014-11 | ||
+ | | style="background-color:#1a9851" |Randomized (C) | ||
+ | |[[#Trastuzumab_monotherapy_2|Trastuzumab]] x 1 y | ||
+ | | style="background-color:#ffffbf" |Inconclusive whether non-inferior DFS (primary endpoint) | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | ''Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.'' | |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, TC portion (cycles 1 to 4)==== | ||
+ | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, H portion (cycles 5 to 22)==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 5: 8 mg/kg IV once on day 1 | ||
+ | **Cycles 6 to 22: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycle for 22 cycles (TC x 4; H x 18)''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''RESPECT:''' Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. [https://doi.org/10.1200/jco.20.00184 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/32936713/ PubMed] [https://clinicaltrials.gov/study/NCT01104935 NCT01104935] | ||
− | ===Regimen {{#subobject: | + | ==TH-FEC (Docetaxel) {{#subobject:hic977|Regimen=1}}== |
− | {| | + | TH-FEC: '''<u>T</u>'''axotere (Docetaxel) & '''<u>H</u>'''erceptin (Trastuzumab), followed by '''<u>F</u>'''luorouracil, '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide |
− | | | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | |[[Levels_of_Evidence#Evidence| | + | ===Regimen variant #1 {{#subobject:bt7xr7|Variant=1}}=== |
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |rowspan=2|[https://doi.org/10.1056/NEJMoa053028 Joensuu et al. 2006 (FinHer)] | ||
+ | |rowspan=2|2000-2003 | ||
+ | |rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |1. [[Breast_cancer,_HER2-positive_-_historical#D-FEC|D-FEC]]<br>2. [[Breast_cancer,_HER2-positive_-_historical#V-FEC|V-FEC]] | ||
+ | | style="background-color:#1a9850" |Superior RFS (primary endpoint)<br>Median RFS: NYR vs NYR<br>(HR 0.42, 95% CI 0.21-0.83) | ||
|- | |- | ||
− | |[ | + | |3. [[#VH-FEC|VH-FEC]] |
− | |style="background-color:# | + | |style="background-color:#d3d3d3"|Not reported |
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
− | ==== | + | ====Preceding treatment==== |
− | + | *[[Surgery#Breast_cancer_surgery|Surgery]] | |
− | *[[ | + | </div> |
− | *[[ | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[Trastuzumab (Herceptin)]] 4 mg/kg IV | + | ====Chemotherapy, TH portion (cycles 1 to 3)==== |
− | + | *[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1 | |
− | ==== | + | ====Targeted therapy, TH portion (cycles 1 to 3)==== |
− | * | + | *[[Trastuzumab (Herceptin)]] as follows: |
− | + | **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15 | |
− | + | **Cycles 2 & 3: 2 mg/kg IV once per day on days 1, 8, 15 | |
− | + | ====Chemotherapy, FEC portion (cycles 4 to 6)==== | |
− | + | *[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once on day 1 | |
− | + | *[[Epirubicin (Ellence)]] 60 mg/m<sup>2</sup> IV once on day 1 | |
− | *[[ | + | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 |
− | + | '''21-day cycle for 6 cycles (TH x 3; FEC x 3)''' | |
− | '''21-day cycles | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | === | + | ===Regimen variant #2, 600/75/600 x 3 {{#subobject:b0f889|Variant=1}}=== |
− | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" | |
− | + | !style="width: 33%"|Study | |
− | + | !style="width: 33%"|Dates of enrollment | |
− | + | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6143012/ Joensuu et al. 2018 (SOLD)] | ||
+ | |2008-2014 | ||
+ | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
− | ===Regimen {{#subobject: | + | ====Preceding treatment==== |
− | {| | + | *[[Surgery#Breast_cancer_surgery|Surgery]] |
− | | | + | </div> |
− | |[[Levels_of_Evidence#Evidence| | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | + | ====Chemotherapy, TH portion (cycles 1 to 3)==== | |
− | + | *[[Docetaxel (Taxotere)]] 80 mg/m<sup>2</sup> IV once on day 1 | |
+ | ====Targeted therapy, TH portion (cycles 1 to 3)==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycles 2 & 3: 6 mg/kg IV once on day 1 | ||
+ | ====Chemotherapy, FEC portion (cycles 4 to 6)==== | ||
+ | *[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | '''21-day cycle for 6 cycles (TH x 3; FEC x 3)''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[#Trastuzumab_monotherapy_2|Trastuzumab]] maintenance for a total of 1 year versus [[Breast_cancer,_HER2-positive_-_null_regimens#Observation|no further treatment]] | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #3 {{#subobject:f18df7|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https://www.ncbi.nlm.nih.gov/pmc/articles/ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6143012/ Joensuu et al. 2018 (SOLD)] |
− | | | + | |2008-2014 |
− | + | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT | |
− | |style="background-color:# | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
− | ====Chemotherapy==== | + | ====Preceding treatment==== |
− | *[[Docetaxel (Taxotere)]] | + | *[[Surgery#Breast_cancer_surgery|Surgery]] |
− | + | </div> | |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | + | ====Chemotherapy, TH portion (cycles 1 to 3)==== | |
+ | *[[Docetaxel (Taxotere)]] 80 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy, TH portion (cycles 1 to 3)==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle 1: | + | **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15 |
− | ** | + | **Cycles 2 & 3: 2 mg/kg IV once per day on days 1, 8, 15 |
− | *[[ | + | ====Chemotherapy, FEC portion (cycles 4 to 6)==== |
− | * | + | *[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once on day 1 |
− | * | + | *[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1 |
− | + | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | |
− | '''21-day cycle for | + | '''21-day cycle for 6 cycles (TH x 3; FEC x 3)''' |
− | + | </div> | |
− | === | + | <div class="toccolours" style="background-color:#cbd5e7"> |
− | # | + | ====Subsequent treatment==== |
− | + | *[[#Trastuzumab_monotherapy_2|Trastuzumab]] maintenance for a total of 1 year versus [[Breast_cancer,_HER2-positive_-_null_regimens#Observation|no further treatment]] | |
− | + | </div></div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
+ | ===Regimen variant #4 {{#subobject:bea44d|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6143012/ Joensuu et al. 2018 (SOLD)] | ||
+ | |2008-2014 | ||
+ | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT | ||
|- | |- | ||
− | |||
|} | |} | ||
− | TH: | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | ===Regimen {{#subobject: | + | ====Preceding treatment==== |
− | {| | + | *[[Surgery#Breast_cancer_surgery|Surgery]] |
− | | | + | </div> |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | + | ====Chemotherapy, TH portion (cycles 1 to 3)==== | |
− | + | *[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1 | |
− | + | ====Targeted therapy, TH portion (cycles 1 to 3)==== | |
− | + | *[[Trastuzumab (Herceptin)]] as follows: | |
− | + | **Cycle 1: 8 mg/kg IV once on day 1 | |
− | |[[# | + | **Cycles 2 & 3: 6 mg/kg IV once on day 1 |
− | + | ====Chemotherapy, FEC portion (cycles 4 to 6)==== | |
+ | *[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | '''21-day cycle for 6 cycles (TH x 3; FEC x 3)''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[#Trastuzumab_monotherapy_2|Trastuzumab]] maintenance for a total of 1 year versus [[Breast_cancer,_HER2-positive_-_null_regimens#Observation|no further treatment]] | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #5 {{#subobject:8a1397|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6143012/ Joensuu et al. 2018 (SOLD)] |
− | |style="background-color:# | + | |2008-2014 |
+ | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT | ||
|- | |- | ||
|} | |} | ||
− | ====Chemotherapy, TH portion==== | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | *[[ | + | ====Preceding treatment==== |
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, TH portion (cycles 1 to 3)==== | ||
+ | *[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1 | ||
+ | ====Targeted therapy, TH portion (cycles 1 to 3)==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once on | + | **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15 |
− | **Cycles 2 | + | **Cycles 2 & 3: 2 mg/kg IV once per day on days 1, 8, 15 |
+ | ====Chemotherapy, FEC portion (cycles 4 to 6)==== | ||
+ | *[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | '''21-day cycle for 6 cycles (TH x 3; FEC x 3)''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[#Trastuzumab_monotherapy_2|Trastuzumab]] maintenance for a total of 1 year versus [[Breast_cancer,_HER2-positive_-_null_regimens#Observation|no further treatment]] | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | <!-- no pre-pub disclosed --> | ||
+ | # '''FinHer:''' Joensuu H, Kellokumpu-Lehtinen PL, Bono P, Alanko T, Kataja V, Asola R, Utriainen T, Kokko R, Hemminki A, Tarkkanen M, Turpeenniemi-Hujanen T, Jyrkkiö S, Flander M, Helle L, Ingalsuo S, Johansson K, Jääskeläinen AS, Pajunen M, Rauhala M, Kaleva-Kerola J, Salminen T, Leinonen M, Elomaa I, Isola J; FinHer Study Investigators. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006 Feb 23;354(8):809-20. [https://doi.org/10.1056/NEJMoa053028 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16495393/ PubMed] ISRCTN76560285 | ||
+ | ## '''Update:''' Joensuu H, Bono P, Kataja V, Alanko T, Kokko R, Asola R, Utriainen T, Turpeenniemi-Hujanen T, Jyrkkiö S, Möykkynen K, Helle L, Ingalsuo S, Pajunen M, Huusko M, Salminen T, Auvinen P, Leinonen H, Leinonen M, Isola J, Kellokumpu-Lehtinen PL. Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer trial. J Clin Oncol. 2009 Dec 1;27(34):5685-92. Epub 2009 Nov 2. [https://doi.org/10.1200/JCO.2008.21.4577 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19884557/ PubMed] | ||
+ | # '''SOLD:''' Joensuu H, Fraser J, Wildiers H, Huovinen R, Auvinen P, Utriainen M, Nyandoto P, Villman KK, Halonen P, Granstam-Björneklett H, Lundgren L, Sailas L, Turpeenniemi-Hujanen T, Tanner M, Yachnin J, Ritchie D, Johansson O, Huttunen T, Neven P, Canney P, Harvey VJ, Kellokumpu-Lehtinen PL, Lindman H. Effect of adjuvant trastuzumab for a duration of 9 weeks vs 1 year with concomitant chemotherapy for early human epidermal growth factor receptor 2-positive breast cancer: the SOLD randomized clinical trial. JAMA Oncol. 2018 Sep 1;4(9):1199-1206. [https://doi.org/10.1001/jamaoncol.2018.1380 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6143012/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29852043/ PubMed] [https://clinicaltrials.gov/study/NCT00593697 NCT00593697] | ||
− | === | + | ==TH-FEC (Docetaxel, SC Trastuzumab) {{#subobject:b8bf2c|Regimen=1}}== |
− | + | TH-FEC: '''<u>T</u>'''axotere (Docetaxel) & '''<u>H</u>'''erceptin Hylecta (Trastuzumab and hyaluronidase), followed by '''<u>F</u>'''luorouracil, '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #1, 80 x 3, q3wk trastuzumab {{#subobject:92b8bf|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" | |
− | + | !style="width: 33%"|Study | |
− | + | !style="width: 33%"|Dates of enrollment | |
− | + | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | ''' | ||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | ''' | ||
− | |||
− | ===Regimen # | ||
− | {| | ||
− | | | ||
− | |[[Levels_of_Evidence#Evidence| | ||
|- | |- | ||
− | |[https://www.ncbi.nlm.nih.gov/pmc/articles/ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6143012/ Joensuu et al. 2018 (SOLD)] |
− | |style="background-color:# | + | |2008-2014 |
+ | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT | ||
|- | |- | ||
|} | |} | ||
− | ====Chemotherapy, TH portion==== | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | *[[ | + | ====Preceding treatment==== |
− | *[[Trastuzumab (Herceptin)]] | + | *[[Surgery#Breast_cancer_surgery|Surgery]] |
− | + | </div> | |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | + | ====Chemotherapy, TH portion (cycles 1 to 3)==== | |
− | ==== | + | *[[Docetaxel (Taxotere)]] 80 mg/m<sup>2</sup> IV once on day 1 |
− | * | + | ====Targeted therapy, TH portion (cycles 1 to 3)==== |
− | + | *[[Trastuzumab and hyaluronidase (Herceptin Hylecta)]] 600 mg/10,000 units SC once on day 1 | |
− | + | ====Chemotherapy, FEC portion (cycles 4 to 6)==== | |
− | + | *[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once on day 1 | |
− | ''' | + | *[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1 |
− | + | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | |
− | === | + | '''21-day cycle for 6 cycles (TH x 3; FEC x 3)''' |
− | # | + | </div> |
− | + | <div class="toccolours" style="background-color:#cbd5e7"> | |
− | < | + | ====Subsequent treatment==== |
− | # | + | *[[#Trastuzumab_monotherapy_2|trastuzumab]] maintenance for a total of 1 year versus [[Breast_cancer,_HER2-positive_-_null_regimens#Observation|no further treatment]] |
− | + | </div></div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | {| class="wikitable" style=" | + | ===Regimen variant #2, 100 x 3, q3wk trastuzumab {{#subobject:eb48a0|Variant=1}}=== |
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6143012/ Joensuu et al. 2018 (SOLD)] | |
− | + | |2008-2014 | |
− | + | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | | | ||
− | |||
− | |style="background-color:# | ||
− | |||
− | |||
− | |||
|- | |- | ||
|} | |} | ||
− | ====Chemotherapy, | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | *[[ | + | ====Preceding treatment==== |
− | + | *[[Surgery#Breast_cancer_surgery|Surgery]] | |
− | ==== | + | </div> |
− | *[[ | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | + | ====Chemotherapy, TH portion (cycles 1 to 3)==== | |
− | + | *[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1 | |
− | + | ====Targeted therapy, TH portion (cycles 1 to 3)==== | |
− | + | *[[Trastuzumab and hyaluronidase (Herceptin Hylecta)]] 600 mg/10,000 units SC once on day 1 | |
− | + | ====Chemotherapy, FEC portion (cycles 4 to 6)==== | |
− | + | *[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once on day 1 | |
− | + | *[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV once on day 1 | |
− | + | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | |
− | + | '''21-day cycle for 6 cycles (TH x 3; FEC x 3)''' | |
− | + | </div> | |
− | + | <div class="toccolours" style="background-color:#cbd5e7"> | |
− | + | ====Subsequent treatment==== | |
− | + | *[[#Trastuzumab_monotherapy_2|trastuzumab]] maintenance for a total of 1 year versus [[Breast_cancer,_HER2-positive_-_null_regimens#Observation|no further treatment]] | |
− | ''' | + | </div></div> |
− | |||
− | ==== | ||
− | |||
− | *[[ | ||
− | |||
− | |||
− | |||
− | |||
===References=== | ===References=== | ||
− | # | + | # '''SOLD:''' Joensuu H, Fraser J, Wildiers H, Huovinen R, Auvinen P, Utriainen M, Nyandoto P, Villman KK, Halonen P, Granstam-Björneklett H, Lundgren L, Sailas L, Turpeenniemi-Hujanen T, Tanner M, Yachnin J, Ritchie D, Johansson O, Huttunen T, Neven P, Canney P, Harvey VJ, Kellokumpu-Lehtinen PL, Lindman H. Effect of adjuvant trastuzumab for a duration of 9 weeks vs 1 year with concomitant chemotherapy for early human epidermal growth factor receptor 2-positive breast cancer: the SOLD randomized clinical trial. JAMA Oncol. 2018 Sep 1;4(9):1199-1206. [https://doi.org/10.1001/jamaoncol.2018.1380 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6143012/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29852043/ PubMed] [https://clinicaltrials.gov/study/NCT00593697 NCT00593697] |
− | # | + | ==VH-FEC {{#subobject:ca8dff|Regimen=1}}== |
− | + | VH-FEC: '''<u>V</u>'''inorelbine & '''<u>H</u>'''erceptin (Trastuzumab), followed by '''<u>F</u>'''luorouracil, '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide | |
− | == | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style=" | + | ===Regimen {{#subobject:f78da8|Variant=1}}=== |
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |rowspan=2|[https://doi.org/10.1056/NEJMoa053028 Joensuu et al. 2006 (FinHer)] |
− | + | |rowspan=2|2000-2003 | |
− | + | |rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc) | |
− | + | |1. [[Breast_cancer,_HER2-positive_-_historical#D-FEC|D-FEC]]<br>2. [[Breast_cancer,_HER2-positive_-_historical#V-FEC|V-FEC]] | |
− | = | + | | style="background-color:#1a9850" |Superior RFS (primary endpoint)<br>Median RFS: NYR vs NYR<br>(HR 0.42, 95% CI 0.21-0.83) |
− | |||
− | | | ||
− | |[[ | ||
− | |||
− | |||
|- | |- | ||
− | | | + | |3. [[#TH-FEC_.28Docetaxel.29|TH-FEC]] |
− | |||
− | |||
− | |||
− | |||
− | |||
|style="background-color:#d3d3d3"|Not reported | |style="background-color:#d3d3d3"|Not reported | ||
|- | |- | ||
|} | |} | ||
− | ====Chemotherapy, | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | *[[ | + | ====Preceding treatment==== |
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy, VH portion (cycles 1 to 3)==== | ||
+ | *[[Vinorelbine (Navelbine)]] as follows: | ||
+ | **Cycles 1 & 2: 25 mg/m<sup>2</sup> IV over 5 to 10 minutes once per day on days 1, 8, 15 | ||
+ | **Cycle 3: 25 mg/m<sup>2</sup> IV over 5 to 10 minutes once per day on days 1 & 8 | ||
+ | ====Targeted therapy, VH portion (cycles 1 to 3)==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15 | + | **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15 |
**Cycles 2 & 3: 2 mg/kg IV once per day on days 1, 8, 15 | **Cycles 2 & 3: 2 mg/kg IV once per day on days 1, 8, 15 | ||
− | + | ====Chemotherapy, FEC portion (cycles 4 to 6)==== | |
− | |||
− | |||
− | ====Chemotherapy, FEC portion==== | ||
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once on day 1 | *[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | *[[Epirubicin (Ellence)]] 60 mg/m<sup>2</sup> IV once on day 1 | + | *[[Epirubicin (Ellence)]] 60 mg/m<sup>2</sup> IV once on day 1 |
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | *[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | '''21-day cycle for 6 cycles (VH x 3; FEC x 3)''' | |
− | '''21-day cycle for 3 | + | </div></div> |
− | |||
− | |||
− | |||
− | |||
===References=== | ===References=== | ||
<!-- no pre-pub disclosed --> | <!-- no pre-pub disclosed --> | ||
− | # Joensuu H, Kellokumpu-Lehtinen PL, Bono P, Alanko T, Kataja V, Asola R, Utriainen T, Kokko R, Hemminki A, Tarkkanen M, Turpeenniemi-Hujanen T, Jyrkkiö S, Flander M, Helle L, Ingalsuo S, Johansson K, Jääskeläinen AS, Pajunen M, Rauhala M, Kaleva-Kerola J, Salminen T, Leinonen M, Elomaa I, Isola J; FinHer Study Investigators. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006 Feb 23;354(8):809-20. [ | + | # '''FinHer:''' Joensuu H, Kellokumpu-Lehtinen PL, Bono P, Alanko T, Kataja V, Asola R, Utriainen T, Kokko R, Hemminki A, Tarkkanen M, Turpeenniemi-Hujanen T, Jyrkkiö S, Flander M, Helle L, Ingalsuo S, Johansson K, Jääskeläinen AS, Pajunen M, Rauhala M, Kaleva-Kerola J, Salminen T, Leinonen M, Elomaa I, Isola J; FinHer Study Investigators. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006 Feb 23;354(8):809-20. [https://doi.org/10.1056/NEJMoa053028 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16495393/ PubMed] ISRCTN76560285 |
− | ## '''Update:''' Joensuu H, Bono P, Kataja V, Alanko T, Kokko R, Asola R, Utriainen T, Turpeenniemi-Hujanen T, Jyrkkiö S, Möykkynen K, Helle L, Ingalsuo S, Pajunen M, Huusko M, Salminen T, Auvinen P, Leinonen H, Leinonen M, Isola J, Kellokumpu-Lehtinen PL. Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer | + | ## '''Update:''' Joensuu H, Bono P, Kataja V, Alanko T, Kokko R, Asola R, Utriainen T, Turpeenniemi-Hujanen T, Jyrkkiö S, Möykkynen K, Helle L, Ingalsuo S, Pajunen M, Huusko M, Salminen T, Auvinen P, Leinonen H, Leinonen M, Isola J, Kellokumpu-Lehtinen PL. Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer trial. J Clin Oncol. 2009 Dec 1;27(34):5685-92. Epub 2009 Nov 2. [https://doi.org/10.1200/JCO.2008.21.4577 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19884557/ PubMed] |
− | == | + | =Adjuvant therapy= |
− | {| class="wikitable" style=" | + | ==Docetaxel & Trastuzumab (TH) {{#subobject:a0af2c|Regimen=1}}== |
+ | TH: '''<u>T</u>'''axotere (Docetaxel) & '''<u>H</u>'''erceptin (Trastuzumab) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, 75 x 4, q3wk trastuzumab {{#subobject:2fb74a|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.20.00184 Sawaki et al. 2020 (RESPECT)] | ||
+ | |2009-10 to 2014-11 | ||
+ | | style="background-color:#1a9851" |Randomized (C) | ||
+ | |[[#Trastuzumab_monotherapy_2|Trastuzumab]] x 12 mo | ||
+ | |style="background-color:#ffffbf"|Inconclusive whether non-inferior DFS | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
− | + | ====Preceding treatment==== | |
− | ===Regimen {{#subobject: | + | *[[Surgery#Breast_cancer_surgery|Surgery]] |
− | {| | + | </div> |
− | | | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | |[[Levels_of_Evidence#Evidence| | + | ====Chemotherapy==== |
− | | | + | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 |
− | |[[Levels_of_Evidence# | + | ====Targeted therapy==== |
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycles 2 to 4: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycle for 4 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[#Trastuzumab_monotherapy_2|Trastuzumab]] maintenance (q3wk) for a total of 1 year | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, 75 x 4, weekly trastuzumab {{#subobject:5cbacf|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872016/ Piccart-Gebhart et al. 2015 (ALTTO)] | |
− | | | + | |2007-2011 |
− | |[[ | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | + | |1. [[#TH-L_999|TH-L]]<br>2. [[#THL_.28Docetaxel.29_999|THL (Taxotere)]]<br>3. [[Stub#Docetaxel_.26_Lapatinib_.28TL.29|TL (Docetaxel)]] | |
− | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS | |
− | |||
− | |style="background-color:# | ||
|- | |- | ||
|} | |} | ||
− | ====Chemotherapy | + | ''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' |
− | *[[ | + | <div class="toccolours" style="background-color:#cbd5e8"> |
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]], then adjuvant [[Regimen_classes#Anthracycline-based_regimen|anthracycline-based chemotherapy]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
**Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15 | **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15 | ||
− | **Cycles 2 | + | **Cycles 2 to 4: 2 mg/kg IV once per day on days 1, 8, 15 |
− | + | '''21-day cycle for 4 cycles''' | |
− | '''21-day cycle for | + | </div> |
− | + | <div class="toccolours" style="background-color:#cbd5e7"> | |
− | ==== | + | ====Subsequent treatment==== |
− | *[[ | + | *[[#Trastuzumab_monotherapy_2|Trastuzumab]] maintenance (q3wk) for a total of 1 year |
− | + | </div></div> | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
===References=== | ===References=== | ||
− | + | # '''ALTTO:''' Piccart-Gebhart M, Holmes E, Baselga J, de Azambuja E, Dueck AC, Viale G, Zujewski JA, Goldhirsch A, Armour A, Pritchard KI, McCullough AE, Dolci S, McFadden E, Holmes AP, Tonghua L, Eidtmann H, Dinh P, Di Cosimo S, Harbeck N, Tjulandin S, Im YH, Huang CS, Diéras V, Hillman DW, Wolff AC, Jackisch C, Lang I, Untch M, Smith I, Boyle F, Xu B, Gomez H, Suter T, Gelber RD, Perez EA. Adjuvant lapatinib and trastuzumab for early human epidermal growth factor receptor 2-positive breast cancer: results from the randomized phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial. J Clin Oncol. 2016 Apr 1;34(10):1034-42. Epub 2015 Nov 23. [https://doi.org/10.1200/JCO.2015.62.1797 link to original article] [https://ascopubs.org/doi/suppl/10.1200/JCO.2015.62.1797/suppl_file/protocol_2015.621797.pdf link to protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872016/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26598744/ PubMed] [https://clinicaltrials.gov/study/NCT00490139 NCT00490139] | |
− | + | ##'''Update:''' Moreno-Aspitia A, Holmes EM, Jackisch C, de Azambuja E, Boyle F, Hillman DW, Korde L, Fumagalli D, Izquierdo MA, McCullough AE, Wolff AC, Pritchard KI, Untch M, Guillaume S, Ewer MS, Shao Z, Sim SH, Aziz Z, Demetriou G, Mehta AO, Andersson M, Toi M, Lang I, Xu B, Smith IE, Barrios CH, Baselga J, Gelber RD, Piccart-Gebhart M; ALTTO Steering Committee and Investigators. Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D). Eur J Cancer. 2021 May;148:287-296. Epub 2021 Mar 23. [https://doi.org/10.1016/j.ejca.2021.01.053 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103014/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33765513/ PubMed] | |
− | ## '''Update:''' | + | # '''RESPECT:''' Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. [https://doi.org/10.1200/jco.20.00184 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/32936713/ PubMed] [https://clinicaltrials.gov/study/NCT01104935 NCT01104935] |
− | + | ==CMF & H {{#subobject:ygvn46|Regimen=1}}== | |
− | == | + | CMF & H: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>H</u>'''erceptin (Trastuzumab) |
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen {{#subobject:cn47b2|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.20.00184 Sawaki et al. 2020 (RESPECT)] |
− | + | |2009-10 to 2014-11 | |
− | + | | style="background-color:#1a9851" |Randomized (C) | |
− | + | |[[#Trastuzumab_monotherapy_2|Trastuzumab]] x 1 y | |
− | + | | style="background-color:#ffffbf" |Inconclusive whether non-inferior DFS (primary endpoint) | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | | | ||
− | |||
− | |style="background-color:# | ||
− | | | ||
− | |Trastuzumab x | ||
− | |style="background-color:# | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm. The protocol document reported a flat dose of oral cyclophosphamide, but this would not be consistent with any other known CMF variants; dosing below is provided as BSA-based.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
+ | *[[Cyclophosphamide (Cytoxan)]] as follows: | ||
+ | **Cycles 1 to 6: 75 to 100 mg/m<sup>2</sup> PO once per day on days 1 to 14 | ||
+ | *[[Methotrexate (MTX)]] as follows: | ||
+ | **Cycles 1 to 6: 40 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
+ | *[[Fluorouracil (5-FU)]] as follows: | ||
+ | **Cycles 1 to 6: 500 to 600 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
+ | ====Targeted therapy==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle 1: 8 mg/kg IV | + | **Cycle 1: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 2 to 18: 6 mg/kg IV once on day 1 |
− | + | '''21-day cycle for 18 cycles (1 year)''' | |
− | ''' | + | </div></div> |
− | + | ===References=== | |
− | ===Regimen # | + | # '''RESPECT:''' Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. [https://doi.org/10.1200/jco.20.00184 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/32936713/ PubMed] [https://clinicaltrials.gov/study/NCT01104935 NCT01104935] |
− | {| | + | ==FEC {{#subobject:3613b7|Regimen=1}}== |
− | | | + | FEC: '''<u>F</u>'''luorouracil, '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide |
− | |[[Levels_of_Evidence#Evidence| | + | <br>CEF: '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''pirubicin, '''<u>F</u>'''luorouracil |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #1, 500/100/500 x 3 ("FEC 100") {{#subobject:99d167|Variant=1}}=== | |
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | + | |[https://doi.org/10.1016/S0140-6736(11)61847-3 Baselga et al. 2012 (NeoALTTO)] | |
− | | | + | |2008-2010 |
− | + | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT | |
− | |style="background-color:# | ||
− | |||
− | |||
− | |||
|- | |- | ||
|} | |} | ||
− | '' | + | ''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[ | + | *[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once on day 1 |
− | * | + | *[[Epirubicin (Ellence)]] 100 mg/m<sup>2</sup> IV once on day 1 |
− | * | + | *[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1 |
− | + | '''21-day cycle for 3 cycles''' | |
− | ''' | + | </div> |
− | + | <div class="toccolours" style="background-color:#cbd5e7"> | |
+ | ====Subsequent treatment==== | ||
+ | *[[#Lapatinib_monotherapy_999|Lapatinib]] or [[#Lapatinib_.26_Trastuzumab_2|Lapatinib & Trastuzumab]] or [[#Trastuzumab_monotherapy_2|Trastuzumab]] maintenance, according to initial randomization | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # | + | # '''NeoALTTO:''' Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. [https://doi.org/10.1016/S0140-6736(11)61847-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705192/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22257673/ PubMed] [https://clinicaltrials.gov/study/NCT00553358 NCT00553358] |
− | + | ## '''Update:''' de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. Epub 2014 Aug 14. [https://doi.org/10.1016/S1470-2045(14)70320-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25130998/ PubMed] | |
− | ## '''Update:''' | + | ## '''Update:''' Huober J, Holmes E, Baselga J, de Azambuja E, Untch M, Fumagalli D, Sarp S, Lang I, Smith I, Boyle F, Xu B, Lecocq C, Wildiers H, Jouannaud C, Hackman J, Dasappa L, Ciruelos E, Toral Pena JC, Adamchuk H, Hickish T, de la Pena L, Jackisch C, Gelber RD, Piccart-Gebhart M, Di Cosimo S. Survival outcomes of the NeoALTTO study (BIG 1-06): updated results of a randomised multicenter phase III neoadjuvant clinical trial in patients with HER2-positive primary breast cancer. Eur J Cancer. 2019 Sep;118:169-177. Epub 2019 Aug 1. [https://doi.org/10.1016/j.ejca.2019.04.038 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31377477/ PubMed] |
− | ## '''Update:''' | + | # '''RESPECT:''' Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. [https://doi.org/10.1200/jco.20.00184 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/32936713/ PubMed] [https://clinicaltrials.gov/study/NCT01104935 NCT01104935] |
− | |||
− | = | + | ==FEC & H {{#subobject:bdf58d|Regimen=1}}== |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | == | + | ===Regimen {{#subobject:0b4c6d|Variant=1}}=== |
− | {| class="wikitable" style=" | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/S1470-2045(11)70336-9 Gianni et al. 2011 (NeoSphere)] |
− | + | |2007-2009 | |
− | + | |style="background-color:#91cf61"|Non-randomized part of phase 2 RCT | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | | | ||
− | |||
− | |style="background-color:# | ||
|- | |- | ||
|} | |} | ||
− | + | ''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' | |
− | ''Note: | + | <div class="toccolours" style="background-color:#cbd5e8"> |
+ | ====Preceding treatment==== | ||
+ | *Neoadjuvant [[Stub#Docetaxel_.26_Pertuzumab|Docetaxel & Pertuzumab]] versus [[#THP_.28Docetaxel.29|THP (Docetaxel)]] versus [[#Pertuzumab_.26_Trastuzumab_888|pertuzumab & trastuzumab]] versus [[#Docetaxel_.26_Trastuzumab_.28TH.29|TH (Docetaxel)]], then [[Surgery#Breast_cancer_surgery|surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[ | + | *[[Fluorouracil (5-FU)]] as follows: |
− | *[[Cyclophosphamide (Cytoxan)]] | + | **Cycles 1 to 3: 600 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Trastuzumab (Herceptin)]] | + | *[[Epirubicin (Ellence)]] as follows: |
− | + | **Cycles 1 to 3: 90 mg/m<sup>2</sup> IV once on day 1 | |
+ | *[[Cyclophosphamide (Cytoxan)]] as follows: | ||
+ | **Cycles 1 to 3: 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycle for 18 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *NeoSphere, ER-positive patients: Radiotherapy and/or hormone therapy "per local guidelines" | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # | + | # '''NeoSphere:''' Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, Lluch A, Staroslawska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi G, Szado T, Ratnayake J, Ross G, Valagussa P. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012 Jan;13(1):25-32. Epub 2011 Dec 6. [https://doi.org/10.1016/S1470-2045(11)70336-9 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22153890/ PubMed] [https://clinicaltrials.gov/study/NCT00545688 NCT00545688] |
+ | ## '''Update:''' Gianni L, Pienkowski T, Im YH, Tseng LM, Liu MC, Lluch A, Starosławska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi GV, Magazzù D, McNally V, Douthwaite H, Ross G, Valagussa P. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 2016 Jun;17(6):791-800. Epub 2016 May 11. [https://doi.org/10.1016/S1470-2045(16)00163-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27179402/ PubMed] | ||
− | == | + | ==Lapatinib & Trastuzumab {{#subobject:da072f|Regimen=1}}== |
− | {| class="wikitable" style=" | + | L+T: '''<u>L</u>'''apatinib & '''<u>T</u>'''rastuzumab |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:ec4131|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872016/ Piccart-Gebhart et al. 2015 (ALTTO)] | ||
+ | |rowspan=2|2007-2011 | ||
+ | |rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |1. [[#Lapatinib_monotherapy_888|Lapatinib]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS | ||
+ | |- | ||
+ | |2. [[#Trastuzumab_monotherapy_2|Trastuzumab]] | ||
+ | | style="background-color:#d9ef8b" |Might have superior DFS<sup>1</sup><br>(HR 0.86, 95% CI 0.74-1.00) | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S0140-6736(11)61847-3 Baselga et al. 2012 (NeoALTTO)] | ||
+ | |2008-2010 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |[[Complex_multipart_regimens#NeoALTTO|See link]] | ||
+ | |[[Complex_multipart_regimens#NeoALTTO|See link]] | ||
|- | |- | ||
− | |||
|} | |} | ||
− | === | + | ''<sup>1</sup>Reported efficacy is based on the 2021 update.''<br> |
− | *[[ | + | ''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' |
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
− | === | + | ====Preceding treatment==== |
− | + | *NeoALTTO: [[Surgery#Breast_cancer_surgery|Surgery]], then adjuvant [[Breast_cancer#FEC_2|FEC]] x 3 | |
− | + | </div> | |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | + | ====Targeted therapy==== | |
− | | | + | *[[Lapatinib (Tykerb)]] 1000 mg PO once per day |
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV over 90 minutes once on day 1 | ||
+ | **Cycles 2 to 12: 6 mg/kg IV over 30 minutes once on day 1 | ||
+ | '''21-day cycle for 12 cycles (34-week course)''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''NeoALTTO:''' Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. [https://doi.org/10.1016/S0140-6736(11)61847-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705192/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22257673/ PubMed] [https://clinicaltrials.gov/study/NCT00553358 NCT00553358] | ||
+ | ## '''Update:''' de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. Epub 2014 Aug 14. [https://doi.org/10.1016/S1470-2045(14)70320-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25130998/ PubMed] | ||
+ | ## '''Update:''' Huober J, Holmes E, Baselga J, de Azambuja E, Untch M, Fumagalli D, Sarp S, Lang I, Smith I, Boyle F, Xu B, Lecocq C, Wildiers H, Jouannaud C, Hackman J, Dasappa L, Ciruelos E, Toral Pena JC, Adamchuk H, Hickish T, de la Pena L, Jackisch C, Gelber RD, Piccart-Gebhart M, Di Cosimo S. Survival outcomes of the NeoALTTO study (BIG 1-06): updated results of a randomised multicenter phase III neoadjuvant clinical trial in patients with HER2-positive primary breast cancer. Eur J Cancer. 2019 Sep;118:169-177. Epub 2019 Aug 1. [https://doi.org/10.1016/j.ejca.2019.04.038 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31377477/ PubMed] | ||
+ | # '''ALTTO:''' Piccart-Gebhart M, Holmes E, Baselga J, de Azambuja E, Dueck AC, Viale G, Zujewski JA, Goldhirsch A, Armour A, Pritchard KI, McCullough AE, Dolci S, McFadden E, Holmes AP, Tonghua L, Eidtmann H, Dinh P, Di Cosimo S, Harbeck N, Tjulandin S, Im YH, Huang CS, Diéras V, Hillman DW, Wolff AC, Jackisch C, Lang I, Untch M, Smith I, Boyle F, Xu B, Gomez H, Suter T, Gelber RD, Perez EA. Adjuvant lapatinib and trastuzumab for early human epidermal growth factor receptor 2-positive breast cancer: results from the randomized phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial. J Clin Oncol. 2016 Apr 1;34(10):1034-42. Epub 2015 Nov 23. [https://doi.org/10.1200/JCO.2015.62.1797 link to original article] [https://ascopubs.org/doi/suppl/10.1200/JCO.2015.62.1797/suppl_file/protocol_2015.621797.pdf link to protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872016/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26598744/ PubMed] [https://clinicaltrials.gov/study/NCT00490139 NCT00490139] | ||
+ | ##'''Update:''' Moreno-Aspitia A, Holmes EM, Jackisch C, de Azambuja E, Boyle F, Hillman DW, Korde L, Fumagalli D, Izquierdo MA, McCullough AE, Wolff AC, Pritchard KI, Untch M, Guillaume S, Ewer MS, Shao Z, Sim SH, Aziz Z, Demetriou G, Mehta AO, Andersson M, Toi M, Lang I, Xu B, Smith IE, Barrios CH, Baselga J, Gelber RD, Piccart-Gebhart M; ALTTO Steering Committee and Investigators. Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D). Eur J Cancer. 2021 May;148:287-296. Epub 2021 Mar 23. [https://doi.org/10.1016/j.ejca.2021.01.053 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103014/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33765513/ PubMed] | ||
+ | ==Neratinib monotherapy {{#subobject:3c1a9c|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:d9f619|Variant=1}}=== | ||
+ | {| class="wikitable" style="color:white; background-color:#404040" | ||
+ | |<small>'''FDA-recommended dose'''</small> | ||
|- | |- | ||
− | | | + | |} |
− | |style=" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | |[[# | + | !style="width: 20%"|Study |
− | |style=" | + | !style="width: 20%"|Dates of enrollment |
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/S1470-2045(15)00551-3 Chan et al. 2016 (ExteNET)] |
− | | | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" |
− | + | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-134-1 <span style="color:white;">ESMO-MCBS (NEB)</span>]''' | |
− | |||
− | |||
− | |[ | ||
− | |||
− | |||
− | |||
|- | |- | ||
+ | |} --> | ||
+ | |2009-07-09 to 2011-10-24 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-RT-esc) | ||
+ | |[[Breast_cancer,_HER2-positive_-_null_regimens#Placebo|Placebo]] | ||
+ | |style="background-color:#1a9850"|Superior iDFS<sup>1</sup> (primary endpoint)<br>iDFS60: 90% vs 88%<br>(HR 0.73, 95% CI 0.57-0.92)<br><br>Did not meet secondary endpoint of OS<sup>2</sup><br>OS84: 90.1% vs 90.2%<br>(HR 0.95, 95% CI 0.75-1.21) | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy is based on the 2017 update.''<br> |
− | ==== | + | ''<sup>2</sup>Reported efficacy is based on the 2023 update.'' |
− | *[[ | + | <div class="toccolours" style="background-color:#cbd5e8"> |
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]], then [[Regimen_classes#Trastuzumab-based_regimen|trastuzumab-containing chemotherapy]] or [[Regimen_classes#Trastuzumab-based_regimen|trastuzumab-containing chemotherapy]], then [[Surgery#Breast_cancer_surgery|surgery]] (neoadjuvant or adjuvant) | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | |||
+ | ====Targeted therapy==== | ||
+ | *[[Neratinib (Nerlynx)]] 240 mg PO once per day, taken with food | ||
− | ''' | + | ====Supportive therapy==== |
+ | *(per FDA package insert) | ||
+ | *[[Loperamide (Imodium)]] as follows: | ||
+ | **Weeks 1 & 2: 4 mg PO three times per day | ||
+ | **Weeks 3 to 8: 4 mg PO twice per day | ||
+ | **Weeks 9 to 52: 4 mg PO as needed for diarrhea, not to exceed 16 mg/d | ||
+ | '''12-month course''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # | + | # '''ExteNET:''' Chan A, Delaloge S, Holmes FA, Moy B, Iwata H, Harvey VJ, Robert NJ, Silovski T, Gokmen E, von Minckwitz G, Ejlertsen B, Chia SK, Mansi J, Barrios CH, Gnant M, Buyse M, Gore I, Smith J 2nd, Harker G, Masuda N, Petrakova K, Zotano AG, Iannotti N, Rodriguez G, Tassone P, Wong A, Bryce R, Ye Y, Yao B, Martin M; ExteNET Study Group. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2016 Mar;17(3):367-77. Epub 2016 Feb 10. [https://doi.org/10.1016/S1470-2045(15)00551-3 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26874901/ PubMed] [https://clinicaltrials.gov/study/NCT00878709 NCT00878709] |
− | ## '''Update:''' | + | ## '''Update:''' Martin M, Holmes FA, Ejlertsen B, Delaloge S, Moy B, Iwata H, von Minckwitz G, Chia SKL, Mansi J, Barrios CH, Gnant M, Tomašević Z, Denduluri N, Šeparović R, Gokmen E, Bashford A, Ruiz Borrego M, Kim SB, Jakobsen EH, Ciceniene A, Inoue K, Overkamp F, Heijns JB, Armstrong AC, Link JS, Joy AA, Bryce R, Wong A, Moran S, Yao B, Xu F, Auerbach A, Buyse M, Chan A; ExteNET Study Group. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1688-1700. Epub 2017 Nov 13. [https://doi.org/10.1016/S1470-2045(17)30717-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29146401/ PubMed] |
− | + | ## '''HRQoL analysis:''' Delaloge S, Cella D, Ye Y, Buyse M, Chan A, Barrios CH, Holmes FA, Mansi J, Iwata H, Ejlertsen B, Moy B, Chia SKL, Gnant M, Smichkoska S, Ciceniene A, Martinez N, Filipović S, Ben-Baruch NE, Joy AA, Langkjer ST, Senecal F, de Boer RH, Moran S, Yao B, Bryce R, Auerbach A, Fallowfield L, Martin M. Effects of neratinib on health-related quality of life in women with HER2-positive early-stage breast cancer: longitudinal analyses from the randomized phase III ExteNET trial. Ann Oncol. 2019 Apr 1;30(4):567-574. [https://doi.org/10.1093/annonc/mdz016 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30689703/ PubMed] | |
− | + | ## '''Subgroup analysis:''' Iwata H, Masuda N, Kim SB, Inoue K, Rai Y, Fujita T, Chiu J, Ohtani S, Takahashi M, Miyaki T, Lu YS, Xu B, Yap YS, Bustam A, Yao B, Zhang B, Bryce R, Chan A. Neratinib after trastuzumab-based adjuvant therapy in patients from Asia with early stage HER2-positive breast cancer. Future Oncol. 2019 Jul;15(21):2489-2501. Epub 2019 May 29. [https://doi.org/10.2217/fon-2019-0143 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31140297/ PubMed] | |
− | # | + | ## '''Subgroup analysis:''' Chan A, Moy B, Mansi J, Ejlertsen B, Holmes FA, Chia S, Iwata H, Gnant M, Loibl S, Barrios CH, Somali I, Smichkoska S, Martinez N, Alonso MG, Link JS, Mayer IA, Cold S, Murillo SM, Senecal F, Inoue K, Ruiz-Borrego M, Hui R, Denduluri N, Patt D, Rugo HS, Johnston SRD, Bryce R, Zhang B, Xu F, Wong A, Martin M; ExteNET Study Group. Final Efficacy Results of Neratinib in HER2-positive Hormone Receptor-positive Early-stage Breast Cancer From the Phase III ExteNET Trial. Clin Breast Cancer. 2021 Feb;21(1):80-91.e7. Epub 2020 Oct 6. [https://doi.org/10.1016/j.clbc.2020.09.014 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33183970/ PubMed] |
− | ## '''Update:''' | + | ## '''Update:''' Holmes FA, Moy B, Delaloge S, Chia SKL, Ejlertsen B, Mansi J, Iwata H, Gnant M, Buyse M, Barrios CH, Silovski T, Šeparović R, Bashford A, Zotano AG, Denduluri N, Patt D, Gokmen E, Gore I, Smith JW 2nd, Loibl S, Masuda N, Tomašević Z, Petráková K, DiPrimeo D, Wong A, Martin M, Chan A; ExteNET Study Group. Overall survival with neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): A randomised, double-blind, placebo-controlled, phase 3 trial. Eur J Cancer. 2023 May;184:48-59. Epub 2023 Feb 10. [https://doi.org/10.1016/j.ejca.2023.02.002 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36898233/ PubMed] |
− | == | + | ==Paclitaxel & Trastuzumab (TH) {{#subobject:dc66e8|Regimen=1}}== |
− | {| class="wikitable" style=" | + | TH: '''<u>T</u>'''axol (Paclitaxel) & '''<u>H</u>'''erceptin (Trastuzumab) |
+ | <br> PH: '''<u>P</u>'''aclitaxel & '''<u>H</u>'''erceptin (Trastuzumab) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, weekly paclitaxel, weekly trastuzumab {{#subobject:PPV1|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313867/ Tolaney et al. 2015 (APT)] | ||
+ | |2007-10-29 to 2010-09-03 | ||
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
− | |||
|} | |} | ||
− | ===Regimen {{#subobject: | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | {| | + | ====Preceding treatment==== |
− | | | + | *[[Surgery#Breast_cancer_surgery|Surgery]] |
− | |[[Levels_of_Evidence#Evidence| | + | </div> |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Paclitaxel (Taxol)]] as follows: | ||
+ | **Cycles 1 to 4: 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15 | ||
+ | **Cycles 2 to 18: 2 mg/kg IV once per day on days 1, 8, 15 | ||
+ | '''21-day cycle for 18 cycles (1 year)''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, weekly paclitaxel, weekly then q3wk trastuzumab {{#subobject:6e5b6d|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313867/ Tolaney et al. 2015 (APT)] | ||
+ | |2007-10-29 to 2010-09-03 | ||
+ | |style="background-color:#91cf61"|Phase 2 | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872016/ Piccart-Gebhart et al. 2015 (ALTTO)] |
− | |style="background-color:# | + | |2007-2011 |
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1. [[#TH-L_.28Paclitaxel.29_999|TH-L (Paclitaxel)]]<br>2. [[#THL_.28Paclitaxel.29_999|THL (Paclitaxel)]]<br>3. [[#Lapatinib_.26_Paclitaxel_.28TL.29|TL (Paclitaxel)]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *APT: [[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | *ALTTO: [[Surgery#Breast_cancer_surgery|Surgery]], then adjuvant [[Regimen_classes#Anthracycline-based_regimen|anthracycline-based chemotherapy]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[ | + | *[[Paclitaxel (Taxol)]] as follows: |
− | * | + | **Cycles 1 to 4: 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 |
+ | ====Targeted therapy==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle 1: | + | **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15 |
− | ** | + | **Cycles 2 to 4: 2 mg/kg IV once per day on days 1, 8, 15 |
− | + | **Cycles 5 to 18: 6 mg/kg IV once on day 1 | |
− | '''21-day cycles | + | '''21-day cycle for 18 cycles (1 year)''' |
− | + | </div></div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #3, weekly paclitaxel, q3wk trastuzumab {{#subobject:a4b465|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | + | !style="width: 20%"|Study | |
− | + | !style="width: 20%"|Dates of enrollment | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
− | + | !style="width: 20%"|Comparator | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | |
− | |||
− | ===Regimen {{#subobject: | ||
− | {| | ||
− | | | ||
− | |[[Levels_of_Evidence#Evidence| | ||
− | | | ||
− | |[[Levels_of_Evidence# | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.20.00184 Sawaki et al. 2020 (RESPECT)] |
− | | | + | |2009-10 to 2014-11 |
− | + | | style="background-color:#1a9851" |Randomized (C) | |
− | |style="background-color:# | + | |[[#Trastuzumab_monotherapy_2|Trastuzumab]] x 12 mo |
− | + | |style="background-color:#ffffbf"|Inconclusive whether non-inferior DFS | |
− | |||
− | |||
− | |[[# | ||
− | |style="background-color:# | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[ | + | *[[Paclitaxel (Taxol)]] as follows: |
− | *[[ | + | **Cycles 1 to 4: 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 |
− | + | ====Targeted therapy==== | |
− | '''21-day cycles''' | + | *[[Trastuzumab (Herceptin)]] as follows: |
− | + | **Cycle 1: 8 mg/kg IV once on day 1 | |
+ | **Cycles 2 to 18: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycle for 18 cycles (1 year)''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # | + | # '''CALGB 40101:''' Shulman LN, Cirrincione CT, Berry DA, Becker HP, Perez EA, O'Regan R, Martino S, Atkins JN, Mayer E, Schneider CJ, Kimmick G, Norton L, Muss H, Winer EP, Hudis C. Six Cycles of Doxorubicin and Cyclophosphamide or Paclitaxel Are Not Superior to Four Cycles As Adjuvant Chemotherapy for Breast Cancer in Women With Zero to Three Positive Axillary Nodes: Cancer and Leukemia Group B 40101. J Clin Oncol. 2012 Nov 20;30(33):4071-6. Epub 2012 Jul 23. [https://doi.org/10.1200/jco.2011.40.6405 link to original article] '''does not contain dosing details''' [https://ascopubs.org/doi/suppl/10.1200/jco.2011.40.6405/suppl_file/Protocol.pdf link to study protocol PDF] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494835/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22826271/ PubMed] [https://clinicaltrials.gov/study/NCT00041119 NCT00041119] |
− | ## '''Update:''' | + | ## '''Update:''' Shulman LN, Berry DA, Cirrincione CT, Becker HP, Perez EA, O'Regan R, Martino S, Shapiro CL, Schneider CJ, Kimmick G, Burstein HJ, Norton L, Muss H, Hudis CA, Winer EP. Comparison of doxorubicin and cyclophosphamide versus single-agent paclitaxel as adjuvant therapy for breast cancer in women with 0 to 3 positive axillary nodes: CALGB 40101 (Alliance). J Clin Oncol. 2014 Aug 1;32(22):2311-7. Epub 2014 Jun 16. [https://doi.org/10.1200/jco.2013.53.7142 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105484/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24934787/ PubMed] |
− | ## '''Update:''' | + | <!-- # '''Abstract:''' Tolaney SM, Barry WT, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS, Ellis M, Shapira I, Wolff AC, Carey LA, Overmoyer BA, Partridge AH, Guo H, Hudis CA, Krop IE, Burstein HJ, Winer EP. A phase II study of adjuvant paclitaxel and trastuzumab (APT trial) for node-negative, HER2-positive breast cancer. SABCS 2013, Abstract S1-04.--> |
− | # | + | # '''APT:''' Tolaney SM, Barry WT, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS, Ellis M, Shapira I, Wolff AC, Carey LA, Overmoyer BA, Partridge AH, Guo H, Hudis CA, Krop IE, Burstein HJ, Winer EP. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. N Engl J Med. 2015 Jan 8;372(2):134-41. Erratum in: N Engl J Med. 2015 Nov 12;373(20):1989. [https://doi.org/10.1056/NEJMoa1406281 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313867/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25564897/ PubMed] [https://clinicaltrials.gov/study/NCT00542451 NCT00542451] |
− | ## '''Update:''' | + | ## '''Update:''' Tolaney SM, Guo H, Pernas S, Barry WT, Dillon DA, Ritterhouse L, Schneider BP, Shen F, Fuhrman K, Baltay M, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS, Ellis MJ, Shapira I, Wolff AC, Carey LA, Overmoyer B, Partridge AH, Hudis CA, Krop IE, Burstein HJ, Winer EP. Seven-Year Follow-Up Analysis of Adjuvant Paclitaxel and Trastuzumab Trial for Node-Negative, Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer. J Clin Oncol. 2019 Aug 1;37(22):1868-1875. Epub 2019 Apr 2. [https://doi.org/10.1200/JCO.19.00066 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587424/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30939096/ PubMed] [https://clinicaltrials.gov/study/NCT00542451 NCT00542451] |
+ | ##'''Update:''' Tolaney SM, Tarantino P, Graham N, Tayob N, Parè L, Villacampa G, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS, Ellis MJ, Shapira I, Wolff AC, Carey LA, Barroso-Sousa R, Villagrasa P, DeMeo M, DiLullo M, Zanudo JGT, Weiss J, Wagle N, Partridge AH, Waks AG, Hudis CA, Krop IE, Burstein HJ, Prat A, Winer EP. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: final 10-year analysis of the open-label, single-arm, phase 2 APT trial. Lancet Oncol. 2023 Mar;24(3):273-285. [https://doi.org/10.1016/S1470-2045(23)00051-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36858723/ PubMed] | ||
+ | # '''ALTTO:''' Piccart-Gebhart M, Holmes E, Baselga J, de Azambuja E, Dueck AC, Viale G, Zujewski JA, Goldhirsch A, Armour A, Pritchard KI, McCullough AE, Dolci S, McFadden E, Holmes AP, Tonghua L, Eidtmann H, Dinh P, Di Cosimo S, Harbeck N, Tjulandin S, Im YH, Huang CS, Diéras V, Hillman DW, Wolff AC, Jackisch C, Lang I, Untch M, Smith I, Boyle F, Xu B, Gomez H, Suter T, Gelber RD, Perez EA. Adjuvant lapatinib and trastuzumab for early human epidermal growth factor receptor 2-positive breast cancer: results from the randomized phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial. J Clin Oncol. 2016 Apr 1;34(10):1034-42. Epub 2015 Nov 23. [https://doi.org/10.1200/JCO.2015.62.1797 link to original article] [https://ascopubs.org/doi/suppl/10.1200/JCO.2015.62.1797/suppl_file/protocol_2015.621797.pdf link to protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872016/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26598744/ PubMed] [https://clinicaltrials.gov/study/NCT00490139 NCT00490139] | ||
+ | ##'''Update:''' Moreno-Aspitia A, Holmes EM, Jackisch C, de Azambuja E, Boyle F, Hillman DW, Korde L, Fumagalli D, Izquierdo MA, McCullough AE, Wolff AC, Pritchard KI, Untch M, Guillaume S, Ewer MS, Shao Z, Sim SH, Aziz Z, Demetriou G, Mehta AO, Andersson M, Toi M, Lang I, Xu B, Smith IE, Barrios CH, Baselga J, Gelber RD, Piccart-Gebhart M; ALTTO Steering Committee and Investigators. Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D). Eur J Cancer. 2021 May;148:287-296. Epub 2021 Mar 23. [https://doi.org/10.1016/j.ejca.2021.01.053 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103014/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33765513/ PubMed] | ||
+ | # '''RESPECT:''' Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. [https://doi.org/10.1200/jco.20.00184 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/32936713/ PubMed] [https://clinicaltrials.gov/study/NCT01104935 NCT01104935] | ||
− | == | + | ==Pertuzumab and Trastuzumab hyaluronidase monotherapy {{#subobject:e59oh5|Regimen=1}}== |
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen {{#subobject:056y3c|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/s1470-2045(20)30536-2 Tan et al. 2021 (FeDeriCa)] | ||
+ | |2018-06-14 to 2018-12-24 | ||
+ | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | ''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' | |
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
− | ===Regimen {{#subobject: | + | ====Preceding treatment==== |
− | {| | + | *Neoadjuvant [[#AC-THP_.28Docetaxel.2C_Phesgo.29|AC-THP (Phesgo)]] or [[#ddAC-THP_.28Paclitaxel.2C_Phesgo.29|ddAC-THP (Phesgo)]], then [[Surgery#Breast_cancer_surgery|surgery]] |
− | | | + | </div> |
− | |[[Levels_of_Evidence#Evidence| | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | | | + | ====Targeted therapy==== |
− | |[[Levels_of_Evidence# | + | *[[Pertuzumab and Trastuzumab hyaluronidase (Phesgo)]] 600/600 SC once on day 1 |
+ | '''21-day cycle for 14 cycles (42 weeks)''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''FeDeriCa:''' Tan AR, Im SA, Mattar A, Colomer R, Stroyakovskii D, Nowecki Z, De Laurentiis M, Pierga JY, Jung KH, Schem C, Hogea A, Badovinac Crnjevic T, Heeson S, Shivhare M, Kirschbrown WP, Restuccia E, Jackisch C; FeDeriCa study group. Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection plus chemotherapy in HER2-positive early breast cancer (FeDeriCa): a randomised, open-label, multicentre, non-inferiority, phase 3 study. Lancet Oncol. 2021 Jan;22(1):85-97. Epub 2020 Dec 21. Erratum in: Lancet Oncol. 2021 Feb;22(2):e42. [https://doi.org/10.1016/s1470-2045(20)30536-2 link to original article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33357420/ PubMed] [https://clinicaltrials.gov/study/NCT03493854 NCT03493854] | ||
+ | ==TCH (Docetaxel) {{#subobject:1b999b|Regimen=1}}== | ||
+ | TCH: '''<u>T</u>'''axotere (Docetaxel), '''<u>C</u>'''arboplatin, '''<u>H</u>'''erceptin (Trastuzumab) | ||
+ | <br>TCbH: '''<u>T</u>'''axotere (Docetaxel), '''<u>C</u>'''ar'''<u>b</u>'''oplatin, '''<u>H</u>'''erceptin (Trastuzumab) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, 60/5 {{#subobject:7a75ck|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.20.00184 Sawaki et al. 2020 (RESPECT)] |
− | |style="background-color:# | + | |2009-10 to 2014-11 |
− | |[[ | + | | style="background-color:#1a9851" |Randomized (C) |
− | |style="background-color:# | + | |[[#Trastuzumab_monotherapy_2|Trastuzumab]] x 1 y |
+ | | style="background-color:#ffffbf" |Inconclusive whether non-inferior DFS (primary endpoint) | ||
|- | |- | ||
|} | |} | ||
− | + | ''Note: This was suggested as an "acceptable" dose for elderly patients, given immature safety results of BCIRG 006.'' | |
− | '' | + | <div class="toccolours" style="background-color:#cbd5e8"> |
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[ | + | *[[Docetaxel (Taxotere)]] as follows: |
− | * | + | **Cycles 1 to 6: 60 mg/m<sup>2</sup> IV once on day 1 |
− | *[[ | + | *[[Carboplatin (Paraplatin)]] as follows: |
− | + | **Cycles 1 to 6: AUC 5 IV once on day 1 | |
− | === | + | ====Targeted therapy==== |
− | + | *[[Trastuzumab (Herceptin)]] as follows: | |
− | + | **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15 | |
− | == | + | **Cycles 2 to 6: 2 mg/kg IV once per day on days 1, 8, 15 |
− | {| class="wikitable" style=" | + | **Cycles 7 to 18: 6 mg/kg IV once on day 1 |
+ | '''21-day cycle for 18 cycles (1 year)''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, 75/6, capped carboplatin {{#subobject:99cbd0|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] | ||
+ | |2011-2013 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#AC-THP_.28Paclitaxel.29|AC-THP (Paclitaxel)]]<br>1b. [[#AC-THP_.28Docetaxel.29_2|AC-THP (Docetaxel)]]<br>1c. [[#ddAC-THP_.28Paclitaxel.29_2|ddAC-THP (Paclitaxel)]]<br>1c. [[#ddAC-THP_.28Docetaxel.29|ddAC-THP (Docetaxel)]]<br>1e. [[#EC-THP_.28Paclitaxel.29|EC-THP (Paclitaxel)]]<br>1f. [[#EC-THP_.28Docetaxel.29|EC-THP (Docetaxel)]]<br>1g. [[#ddEC-THP_.28Paclitaxel.29|ddEC-THP (Paclitaxel)]]<br>1h. [[#ddEC-THP_.28Docetaxel.29|ddEC-THP (Docetaxel)]]<br>1i. [[#FAC-THP_.28Paclitaxel.29|FAC-THP (Paclitaxel)]]<br>1j. [[#FAC-THP_.28Docetaxel.29|FAC-THP (Docetaxel)]]<br>1k. [[#FEC-THP_.28Paclitaxel.29|FEC-THP (Paclitaxel)]]<br>1l. [[#FEC-THP_.28Docetaxel.29|FEC-THP (Docetaxel)]]<br>1m. [[#TCHP_.28Docetaxel.29_2|TCHP (Docetaxel)]] | ||
+ | | style="background-color:#d73027" |Inferior IDFS<sup>1</sup> | ||
|- | |- | ||
− | |||
|} | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the 2021 update.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Docetaxel (Taxotere)]] as follows: | ||
+ | **Cycles 1 to 6: 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Carboplatin (Paraplatin)]] as follows: | ||
+ | **Cycles 1 to 6: AUC 6 (maximum dose of 900 mg) IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycles 2 to 18: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycle for up to 18 cycles (1 year)''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
− | ===Regimen {{#subobject: | + | ===Regimen variant #3, 75/6, no cap {{#subobject:7a8d90|Variant=1}}=== |
− | {| | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | | | + | !style="width: 20%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Dates of enrollment |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3268553/ Slamon et al. 2011 (BCIRG 006)] |
− | |style="background-color:# | + | |rowspan=2|2001-2004 |
− | |[[# | + | |rowspan=2 style="background-color:#1a9851"|Phase 3 (E-RT-esc) |
− | |style="background-color:# | + | |1. [[Breast_cancer,_HER2-positive_-_historical#AC-D|AC-D]] |
+ | |style="background-color:#91cf60"|Seems to have superior OS (secondary endpoint) | ||
|- | |- | ||
− | | | + | |2. [[#AC-TH_.28Docetaxel.29|AC-TH]] |
− | + | |style="background-color:#ffffbf"|Did not meet primary endpoint of DFS | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872016/ Piccart-Gebhart et al. 2015 (ALTTO)] |
− | | | + | |2007-2011 |
− | + | |style="background-color:#1a9851"|Phase 3 (C) | |
− | + | |1. [[Stub#TCL_.28Docetaxel.29|TCL]]<br>2. [[#TCbH-L_.28Docetaxel.29|TCH-L]]<br>3. [[Stub#TCHL_.28Docetaxel.29|TCHL]] | |
− | | | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS |
− | |[[ | ||
− | |||
− | |[[ | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.20.00184 Sawaki et al. 2020 (RESPECT)] |
− | |style="background-color:# | + | |2009-10 to 2014-11 |
− | |[[# | + | | style="background-color:#1a9851" |Randomized (C) |
− | |style="background-color:# | + | |[[#Trastuzumab_monotherapy_2|Trastuzumab]] x 1 y |
+ | | style="background-color:#ffffbf" |Inconclusive whether non-inferior DFS (primary endpoint) | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[ | + | *[[Docetaxel (Taxotere)]] as follows: |
− | *[[Trastuzumab (Herceptin)]] 4 mg/kg IV once on day 1 | + | **Cycles 1 to 6: 75 mg/m<sup>2</sup> IV once on day 1 |
− | + | *[[Carboplatin (Paraplatin)]] as follows: | |
− | '''( | + | **Cycles 1 to 6: AUC 6 IV once on day 1 |
− | + | ====Targeted therapy==== | |
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15 | ||
+ | **Cycles 2 to 6: 2 mg/kg IV once per day on days 1, 8, 15 | ||
+ | **Cycles 7 to 18: 6 mg/kg IV once on day 1 | ||
+ | ====Supportive therapy==== | ||
+ | *ALTTO: [[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] use is mandatory (details not provided) | ||
+ | '''21-day cycle for 18 cycles (1 year)''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | <!-- | + | <!-- no pre-pub disclosed --> |
− | # | + | # '''BCIRG 006:''' Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J; Breast Cancer International Research Group. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011 Oct 6;365(14):1273-83. [https://doi.org/10.1056/NEJMoa0910383 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3268553/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21991949/ PubMed] [https://clinicaltrials.gov/study/NCT00021255 NCT00021255] |
− | ## '''Update:''' | + | # '''APHINITY:''' von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [https://doi.org/10.1056/NEJMoa1703643 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28581356/ PubMed] [https://clinicaltrials.gov/study/NCT01358877 NCT01358877] |
+ | ##'''Update:''' Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. [https://doi.org/10.1200/jco.20.01204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33539215/ PubMed] | ||
+ | # '''ALTTO:''' Piccart-Gebhart M, Holmes E, Baselga J, de Azambuja E, Dueck AC, Viale G, Zujewski JA, Goldhirsch A, Armour A, Pritchard KI, McCullough AE, Dolci S, McFadden E, Holmes AP, Tonghua L, Eidtmann H, Dinh P, Di Cosimo S, Harbeck N, Tjulandin S, Im YH, Huang CS, Diéras V, Hillman DW, Wolff AC, Jackisch C, Lang I, Untch M, Smith I, Boyle F, Xu B, Gomez H, Suter T, Gelber RD, Perez EA. Adjuvant lapatinib and trastuzumab for early human epidermal growth factor receptor 2-positive breast cancer: results from the randomized phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial. J Clin Oncol. 2016 Apr 1;34(10):1034-42. Epub 2015 Nov 23. [https://doi.org/10.1200/JCO.2015.62.1797 link to original article] [https://ascopubs.org/doi/suppl/10.1200/JCO.2015.62.1797/suppl_file/protocol_2015.621797.pdf link to protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872016/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26598744/ PubMed] [https://clinicaltrials.gov/study/NCT00490139 NCT00490139] | ||
+ | ##'''Update:''' Moreno-Aspitia A, Holmes EM, Jackisch C, de Azambuja E, Boyle F, Hillman DW, Korde L, Fumagalli D, Izquierdo MA, McCullough AE, Wolff AC, Pritchard KI, Untch M, Guillaume S, Ewer MS, Shao Z, Sim SH, Aziz Z, Demetriou G, Mehta AO, Andersson M, Toi M, Lang I, Xu B, Smith IE, Barrios CH, Baselga J, Gelber RD, Piccart-Gebhart M; ALTTO Steering Committee and Investigators. Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D). Eur J Cancer. 2021 May;148:287-296. Epub 2021 Mar 23. [https://doi.org/10.1016/j.ejca.2021.01.053 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103014/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33765513/ PubMed] | ||
+ | # '''RESPECT:''' Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. [https://doi.org/10.1200/jco.20.00184 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/32936713/ PubMed] [https://clinicaltrials.gov/study/NCT01104935 NCT01104935] | ||
− | == | + | ==TCHP (Docetaxel) {{#subobject:14bd42|Regimen=1}}== |
− | {| class="wikitable" style=" | + | TCHP: '''<u>T</u>'''axotere (Docetaxel), '''<u>C</u>'''arboplatin, '''<u>H</u>'''erceptin (Trastuzumab), '''<u>P</u>'''ertuzumab |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:34a874|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ von Minckwitz et al. 2017 (APHINITY)] |
− | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | |
− | + | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-133-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' | |
− | {| | ||
− | |''' | ||
− | |||
|- | |- | ||
− | |[ | + | |} --> |
− | |style="background-color:# | + | |2011-2013 |
+ | |style="background-color:#1a9851"|Phase 3 (E-RT-esc) | ||
+ | |1a. [[#AC-TH_.28Paclitaxel.29_2|AC-TH (Paclitaxel)]]<br>1b. [[#AC-TH_.28Docetaxel.29|AC-TH (Docetaxel)]]<br>1c. [[#ddAC-TH_.28Paclitaxel.29|ddAC-TH (Paclitaxel)]]<br>1d. [[#ddAC-TH_.28Docetaxel.29|ddAC-TH (Docetaxel)]]<br>1e. [[#EC-TH_.28Paclitaxel.29|EC-TH (Paclitaxel)]]<br>1f. [[#EC-TH_.28Docetaxel.29_2|EC-TH (Docetaxel)]]<br>1g. [[#ddEC-TH_.28Paclitaxel.29|ddEC-TH (Paclitaxel)]]<br>1h. [[#ddEC-TH_.28Docetaxel.29|ddEC-TH (Docetaxel)]]<br>1i. [[#FAC-TH_.28Paclitaxel.29|FAC-TH (Paclitaxel)]]<br>1j. [[#FAC-TH_.28Docetaxel.29|FAC-TH (Docetaxel)]]<br>1k. [[#FEC-TH_.28Paclitaxel.29_2|FEC-TH (Paclitaxel)]]<br>1l. [[#FEC-TH_.28Docetaxel.29|FEC-TH (Docetaxel)]]<br>1m. [[#TCH_.28Docetaxel.29|TCH (Taxotere)]] | ||
+ | | style="background-color:#1a9850" |Superior IDFS<sup>1</sup> (primary endpoint)<br>IDFS72: 91% vs 88%<br>(HR 0.76, 95% CI 0.64-0.91) | ||
|- | |- | ||
|} | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the 2021 update.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[ | + | *[[Docetaxel (Taxotere)]] as follows: |
− | ** | + | **Cycles 1 to 6: 75 mg/m<sup>2</sup> IV once on day 1 |
− | ** | + | *[[Carboplatin (Paraplatin)]] as follows: |
+ | **Cycles 1 to 6: AUC 6 (maximum dose: 900 mg) IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | ** | + | **Cycle 1: 8 mg/kg IV once on day 1 |
− | **Cycle 1 | + | **Cycles 2 to 18: 6 mg/kg IV once on day 1 |
+ | *[[Pertuzumab (Perjeta)]] as follows: | ||
+ | **Cycle 1: 840 mg IV once on day 1 | ||
+ | **Cycles 2 to 18: 420 mg IV once on day 1 | ||
+ | '''21-day cycle for up to 18 cycles (1 year)''' | ||
+ | </div></div> | ||
− | ''' | + | ===References=== |
+ | # '''APHINITY:''' von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. [https://doi.org/10.1056/NEJMoa1703643 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_protocol.pdf link to supplementary protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538020/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28581356/ PubMed] [https://clinicaltrials.gov/study/NCT01358877 NCT01358877] | ||
+ | ##'''Update:''' Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. [https://doi.org/10.1200/jco.20.01204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33539215/ PubMed] | ||
− | '' | + | ==TCyH (Docetaxel) {{#subobject:b0421b|Regimen=1}}== |
− | + | TCyH: '''<u>T</u>'''axotere (Docetaxel), '''<u>Cy</u>'''clophosphamide, '''<u>H</u>'''erceptin (Trastuzumab) | |
− | ===Regimen | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| | + | ===Regimen {{#subobject:d3aba1|Variant=1}}=== |
− | | | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 33%"|Study |
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045%2813%2970384-X Jones et al. 2013 (US Oncology 06-038)] |
− | |style="background-color:# | + | |2007-2009 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]], within 84 days | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | + | *[[Docetaxel (Taxotere)]] as follows: | |
− | *[[ | + | **Cycles 1 to 4: 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1 |
− | + | *[[Cyclophosphamide (Cytoxan)]] as follows: | |
− | Cycles 1 to | + | **Cycles 1 to 4: 600 mg/m<sup>2</sup> IV over 15 to 30 minutes once on day 1 |
− | *[[ | + | ====Targeted therapy==== |
− | **Cycle 1: | + | *[[Trastuzumab (Herceptin)]] as follows: |
− | + | **Cycle 1: 4 mg/kg IV over 90 minutes once on day 1, then 2 mg/kg IV over 30 to 60 minutes once per day on days 8 & 15 | |
− | * | + | **Cycles 2 to 4: 2 mg/kg IV over 30 to 60 minutes once per day on days 1, 8, 15 |
− | + | **Cycles 6 to 18: 6 mg/kg IV once on day 1 | |
− | '''21-day cycle for | + | ====Supportive therapy==== |
− | + | *Use of [[Filgrastim (Neupogen)]] or [[Pegfilgrastim (Neulasta)]] was allowed. | |
+ | *Prophylactic antibiotics were not recommended. | ||
+ | '''21-day cycle for 18 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # | + | # '''US Oncology 06-038:''' Jones SE, Collea R, Paul D, Sedlacek S, Favret AM, Gore I Jr, Lindquist DL, Holmes FA, Allison MA, Brooks BD, Portillo RM, Vukelja SJ, Steinberg MS, Stokoe C, Crockett MW, Wang Y, Asmar L, Robert NJ, O'Shaughnessy J. Adjuvant docetaxel and cyclophosphamide plus trastuzumab in patients with HER2-amplified early stage breast cancer: a single-group, open-label, phase 2 study. Lancet Oncol. 2013 Oct;14(11):1121-8. Epub 2013 Sep 2. [https://doi.org/10.1016/S1470-2045%2813%2970384-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24007746/ PubMed] [https://clinicaltrials.gov/study/NCT00493649 NCT00493649] |
+ | # '''RESPECT:''' Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. [https://doi.org/10.1200/jco.20.00184 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/32936713/ PubMed] [https://clinicaltrials.gov/study/NCT01104935 NCT01104935] | ||
− | == | + | ==Trastuzumab monotherapy {{#subobject:e585d5|Regimen=1}}== |
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #1, 6 mo course {{#subobject:056v24|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615016/ Earl et al. 2019 (PERSEPHONE)] | ||
+ | |2007-2015 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-de-esc) | ||
+ | |[[#Trastuzumab_monotherapy_2|Trastuzumab]] x 12 mo | ||
+ | | style="background-color:#eeee01" |Non-inferior DFS (primary endpoint)<br>DFS48: 89.4% vs 89.8%<br>(HR 1.07, 90% CI 0.93-1.24) | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
− | + | ====Preceding treatment==== | |
− | ===Regimen {{#subobject: | + | *Not explicitly specified (pragmatic trial) |
− | {| | + | </div> |
− | | | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | |[[Levels_of_Evidence#Evidence| | + | ====Targeted therapy==== |
− | + | *[[Trastuzumab (Herceptin)]] as follows: | |
− | + | **Cycle 1: 8 mg/kg IV over 90 minutes once on day 1 | |
+ | **Cycles 2 onwards: 6 mg/kg IV over 90 minutes once on day 1 | ||
+ | '''21-day cycle for 9 cycles (6 months)''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, 30-week course, q3wk {{#subobject:057a24|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/JCO.2017.74.0126 Pivot et al. 2018 (SB3-G31-BC)] |
− | | | + | |2014-04 to 2015-08 |
− | + | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT | |
− | |style="background-color:# | ||
|- | |- | ||
|} | |} | ||
− | ==== | + | ''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' |
− | *[[ | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | + | ====Preceding treatment==== | |
− | *[[Trastuzumab (Herceptin)]] | + | *Neoadjuvant [[#TH-FEC_.26_H_.28Docetaxel.29|TH-FEC & H]], then [[Surgery#Breast_cancer_surgery|surgery]] |
− | + | </div> | |
− | '''21-day cycle for | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | + | ====Targeted therapy==== | |
− | + | *[[Trastuzumab (Herceptin)]] 6 mg/kg IV over 30 minutes once on day 1 | |
− | + | '''21-day cycle for 10 cycles (30-week course)''' | |
− | === | + | </div></div><br> |
− | # | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | + | ===Regimen variant #3, 34-week course, q3wk {{#subobject:aa250f|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | {| class="wikitable" style=" | + | !style="width: 20%"|Study |
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S0140-6736(11)61847-3 Baselga et al. 2012 (NeoALTTO)] | ||
+ | |2008-2010 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[Complex_multipart_regimens#NeoALTTO|See link]] | ||
+ | |[[Complex_multipart_regimens#NeoALTTO|See link]] | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | ''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' | |
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
− | + | ====Preceding treatment==== | |
− | ===Regimen {{#subobject: | + | *[[Surgery#Breast_cancer_surgery|Surgery]], then adjuvant [[Breast_cancer#FEC_2|FEC]] x 3 |
− | {| | + | </div> |
− | | | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | |[[Levels_of_Evidence#Evidence| | + | ====Targeted therapy==== |
− | | | + | *[[Trastuzumab (Herceptin)]] as follows: |
− | |[[Levels_of_Evidence# | + | **Cycle 1: 8 mg/kg IV over 90 minutes once on day 1 |
+ | **Cycles 2 to 12: 6 mg/kg IV over 30 minutes once on day 1 | ||
+ | '''21-day cycle for 12 cycles (34-week course)''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #4, 42-week course, q3wk {{#subobject:ay253f|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1056/NEJMoa1814017 von Minckwitz et al. 2018 (KATHERINE)] |
− | |style="background-color:# | + | |2013-2015 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |[[#Trastuzumab_emtansine_monotherapy|T-DM1]] |
+ | | style="background-color:#d73027" |Inferior IDFS | ||
|- | |- | ||
|} | |} | ||
− | ==== | + | ''Note: the loading dose in cycle 1 was only used if it had been more than 6 weeks since any preceding dose of trastuzumab.'' |
− | *[[ | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | + | ====Preceding treatment==== | |
+ | *[[Surgery#Breast_cancer_surgery|Surgery]], with residual invasive disease | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle 1: | + | **Cycle 1: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycles 2 to 14: 6 mg/kg IV once on day 1 |
− | + | '''21-day cycle for 14 cycles''' | |
− | '''21-day cycle for | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #5, 1-year total course, q3wk {{#subobject:857980|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | ''' | + | !style="width: 20%"|Study |
− | + | !style="width: 20%"|Dates of enrollment | |
− | === | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | + | !style="width: 20%"|Comparator | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | |
− | = | + | |- |
− | # | + | |rowspan=2|[https://doi.org/10.1056/NEJMoa052306 Piccart-Gebhart et al. 2005 (HERA)] |
− | # | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" |
− | + | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-1-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' | |
− | = | + | |- |
− | + | |} --> | |
+ | |rowspan=2|2001-2005 | ||
+ | |rowspan=2 style="background-color:#1a9851"|Phase 3 (E-RT-esc) | ||
+ | |1. [[Breast_cancer,_HER2-positive_-_null_regimens#Observation|No trastuzumab after (neo-)adjuvant chemotherapy]] | ||
+ | |style="background-color:#1a9850"|Superior OS<sup>1</sup> (secondary endpoint)<br>OS144: 79% vs 73%<br>(HR 0.74, 95% CI 0.64-0.86) | ||
+ | |- | ||
+ | |2. [[#Trastuzumab_monotherapy_2|Trastuzumab]] x 2 y | ||
+ | |style="background-color:#ffffbf"|Did not meet primary endpoint of DFS | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S0140-6736(09)61964-4 Gianni et al. 2010 (NOAH)] | ||
+ | |2002-2005 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |[[Complex_multipart_regimens#NOAH|See link]] | ||
+ | | style="background-color:#91cf60" |[[Complex_multipart_regimens#NOAH|See link]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S1470-2045(13)70225-0 Pivot et al. 2013 (PHARE)] | ||
+ | |2006-2010 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#Trastuzumab_monotherapy_2|Trastuzumab]] x 6 mo | ||
+ | |style="background-color:#ffffbf"|Inconclusive whether non-inferior DFS | ||
+ | |- | ||
+ | |rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872016/ Piccart-Gebhart et al. 2015 (ALTTO)] | ||
+ | |rowspan=2|2007-2011 | ||
+ | |rowspan=2 style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1. [[#Lapatinib_monotherapy_999|Lapatinib]]<br>2. [[#T-L_999|T-L]] | ||
+ | |style="background-color:#ffffbf"|Did not meet primary endpoint of DFS | ||
+ | |- | ||
+ | |3. [[#Lapatinib_.26_Trastuzumab_2|Lapatinib & Trastuzumab]] | ||
+ | | style="background-color:#fee08b" |Might have inferior DFS<sup>2</sup> | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615016/ Earl et al. 2019 (PERSEPHONE)] | ||
+ | |2007-2015 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#Trastuzumab_monotherapy_2|Trastuzumab]] x 6 mo | ||
+ | | style="background-color:#eeee01" |Non-inferior DFS | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1093/annonc/mdy414 Conte et al. 2018 (Short-HER)] |
− | + | |2007 to not reported | |
− | + | |style="background-color:#1a9851"|Phase 3 (C) | |
− | + | |[[#Trastuzumab_monotherapy_2|Trastuzumab]] x 9 wks | |
− | + | |style="background-color:#ffffbf"|Inconclusive whether non-inferior DFS | |
− | |||
− | | | ||
− | |[[ | ||
− | | | ||
− | |||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6143012/ Joensuu et al. 2018 (SOLD)] |
− | |style="background-color:# | + | |2008-2014 |
− | | | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |[[Breast_cancer,_HER2-positive_-_null_regimens#Observation|No further treatment]] |
+ | |style="background-color:#ffffbf"|Inconclusive whether non-inferior DFS | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.20.00184 Sawaki et al. 2020 (RESPECT)] |
− | |style="background-color:# | + | |2009-10 to 2014-11 |
− | |[[ | + | |style="background-color:#1a9851"|Randomized (E-de-esc) |
− | |style="background-color:# | + | |1a. [[#AC-H|AC-H]]<br>1b. [[#CMF_.26_H|CMF & H]]<br>1c. [[#CMF-H|CMF-H]]<br> 1d. [[#EC-H|EC-H]]<br>1e. [[#FEC-H|FEC-H]]<br>1f. [[#T-H_.28Paclitaxel.29|T-H (Paclitaxel)]]<br>1g. [[#T-H_.28Docetaxel.29|T-H (Docetaxel)]]<br>1h. [[#TC-H_.28Docetaxel.29|TC-H]]<br>1i. [[#TCH.28Docetaxel.29|TCH]]<br>1j. [[#Paclitaxel_.26_Trastuzumab_.28TH.29_2|TH (Paclitaxel)]]<br>1k. [[#Docetaxel_.26_Trastuzumab_.28TH.29_2|TH (Docetaxel)]] |
+ | |style="background-color:#ffffbf"|Inconclusive whether non-inferior DFS (primary endpoint) | ||
|- | |- | ||
|} | |} | ||
− | ==== | + | ''<sup>1</sup>Reported efficacy for HERA is based on the 2017 update.''<br> |
− | *[[ | + | ''<sup>2</sup>Reported efficacy for ALTTO is based on the 2021 update.''<br> |
− | *[[ | + | ''Note: for patients already receiving trastuzumab prior to transitioning to monotherapy, re-loading is not necessary.'' |
− | * | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | * | + | ====Preceding treatment==== |
+ | *HERA: [[Surgery#Breast_cancer_surgery|surgery]], then at least four cycles of an approved adjuvant [[Regimen_classes#Chemotherapy-based_regimen|chemotherapy regimen]] or at least four cycles of an approved neoadjuvant [[Regimen_classes#Chemotherapy-based_regimen|chemotherapy regimen]], then [[Surgery#Breast_cancer_surgery|surgery]] | ||
+ | *PERSEPHONE: Not explicitly specified (pragmatic trial) | ||
+ | *SOLD: [[Surgery#Breast_cancer_surgery|Surgery]], then adjuvant [[#TH-FEC_.28Docetaxel.29|TH-FEC]] or [[#TH-FEC_.28Docetaxel.2C_SC_Trastuzumab.29|TH-FEC (SC)]] | ||
+ | *Short-HER: [[Surgery#Breast_cancer_surgery|Surgery]], then adjuvant [[Breast_cancer#Cyclophosphamide_.26_Doxorubicin_.28AC.29_2|AC]] x 4 or [[Breast_cancer#Cyclophosphamide_.26_Epirubicin_.28EC.29_2|EC]] x 4, then adjuvant [[#Paclitaxel_.26_Trastuzumab_.28TH.29_2|TH (Paclitaxel)]] or [[#Docetaxel_.26_Trastuzumab_.28TH.29_2|TH (Docetaxel)]] | ||
+ | *RESPECT: [[Surgery#Breast_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
− | ''' | + | ====Targeted therapy==== |
+ | *[[Trastuzumab (Herceptin)]] as follows (see note): | ||
+ | **Cycle 1: 8 mg/kg IV over 90 minutes once on day 1 | ||
+ | **Cycles 2 to 18: 6 mg/kg IV over 90 minutes once on day 1 | ||
+ | '''21-day cycle for 18 cycles (1 year)''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
− | ===Regimen #2 | + | ===Regimen variant #6, 2-year course {{#subobject:2e0aa2|Variant=1}}=== |
− | {| | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | | | + | !style="width: 20%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Dates of enrollment |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |rowspan=2|[https://doi.org/10.1056/NEJMoa052306 Piccart-Gebhart et al. 2005 (HERA)] |
− | |style="background-color:# | + | |rowspan=2|2001-2005 |
− | |[[Breast_cancer# | + | |rowspan=2 style="background-color:#1a9851"|Phase 3 (E-RT-esc) |
− | |style="background-color:# | + | |1. [[Breast_cancer,_HER2-positive_-_null_regimens#Observation|No trastuzumab after (neo-)adjuvant chemotherapy]] |
+ | |style="background-color:#d3d3d3"|Not reported | ||
|- | |- | ||
− | | | + | |2. [[#Trastuzumab_monotherapy_2|Trastuzumab]] x 1 y |
− | + | |style="background-color:#ffffbf"|Did not meet primary endpoint of DFS | |
− | |||
− | |style="background-color:# | ||
− | |||
− | |||
− | |||
− | |||
− | |||
|- | |- | ||
|} | |} | ||
− | ==== | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | *[[ | + | ====Preceding treatment==== |
+ | *HERA: [[Surgery#Breast_cancer_surgery|surgery]], then at least four cycles of an approved adjuvant [[Regimen_classes#Chemotherapy-based_regimen|chemotherapy regimen]] or at least four cycles of an approved neoadjuvant [[Regimen_classes#Chemotherapy-based_regimen|chemotherapy regimen]], then [[Surgery#Breast_cancer_surgery|surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle 1: | + | **Cycle 1: 8 mg/kg IV over 90 minutes once on day 1 |
− | ** | + | **Cycles 2 to 35: 6 mg/kg IV over 90 minutes once on day 1 |
− | + | '''21-day cycle for 35 cycles (2 years)''' | |
− | '''21-day cycle for | + | </div></div> |
− | + | ===References=== | |
− | === | + | # '''HERA:''' Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C, Cameron D, Dowsett M, Barrios CH, Steger G, Huang CS, Andersson M, Inbar M, Lichinitser M, Láng I, Nitz U, Iwata H, Thomssen C, Lohrisch C, Suter TM, Rüschoff J, Suto T, Greatorex V, Ward C, Straehle C, McFadden E, Dolci MS, Gelber RD; Herceptin Adjuvant (HERA) Trial Study Team. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1659-72. [https://doi.org/10.1056/NEJMoa052306 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.nejm.org/doi/suppl/10.1056/NEJMoa052306/suppl_file/nejm_piccart_1659sa1-2.pdf link to data supplement] [https://pubmed.ncbi.nlm.nih.gov/16236737/ PubMed] [https://clinicaltrials.gov/study/NCT00045032 NCT00045032] |
− | + | ## '''Update:''' Smith I, Procter M, Gelber RD, Guillaume S, Feyereislova A, Dowsett M, Goldhirsch A, Untch M, Mariani G, Baselga J, Kaufmann M, Cameron D, Bell R, Bergh J, Coleman R, Wardley A, Harbeck N, Lopez RI, Mallmann P, Gelmon K, Wilcken N, Wist E, Sánchez Rovira P, Piccart-Gebhart MJ; HERA study team. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet. 2007 Jan 6;369(9555):29-36. [https://doi.org/10.1016/S0140-6736(07)60028-2 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17208639/ PubMed] | |
− | + | ## '''Update:''' Gianni L, Dafni U, Gelber RD, Azambuja E, Muehlbauer S, Goldhirsch A, Untch M, Smith I, Baselga J, Jackisch C, Cameron D, Mano M, Pedrini JL, Veronesi A, Mendiola C, Pluzanska A, Semiglazov V, Vrdoljak E, Eckart MJ, Shen Z, Skiadopoulos G, Procter M, Pritchard KI, Piccart-Gebhart MJ, Bell R; Herceptin Adjuvant (HERA) Trial Study Team. Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncol. 2011 Mar;12(3):236-44. Epub 2011 Feb 25. [https://doi.org/10.1016/S1470-2045(11)70033-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21354370/ PubMed] | |
− | ''' | + | ## '''Update:''' Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, de Azambuja E, Procter M, Suter TM, Jackisch C, Cameron D, Weber HA, Heinzmann D, Dal Lago L, McFadden E, Dowsett M, Untch M, Gianni L, Bell R, Köhne CH, Vindevoghel A, Andersson M, Brunt AM, Otero-Reyes D, Song S, Smith I, Leyland-Jones B, Baselga J; Herceptin Adjuvant (HERA) Trial Study Team. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet. 2013 Sep 21;382(9897):1021-8. Epub 2013 Jul 18. [https://doi.org/10.1016/S0140-6736(13)61094-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23871490/ PubMed] |
+ | ## '''Update:''' Cameron D, Piccart-Gebhart MJ, Gelber RD, Procter M, Goldhirsch A, de Azambuja E, Castro G Jr, Untch M, Smith I, Gianni L, Baselga J, Al-Sakaff N, Lauer S, McFadden E, Leyland-Jones B, Bell R, Dowsett M, Jackisch C; Herceptin Adjuvant (HERA) Trial Study Team. 11 years' follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017 Mar 25;389(10075):1195-1205. Epub 2017 Feb 17. [https://doi.org/10.1016/S0140-6736(16)32616-2 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5465633/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28215665/ PubMed] | ||
+ | # '''NOAH:''' Gianni L, Eiermann W, Semiglazov V, Manikhas A, Lluch A, Tjulandin S, Zambetti M, Vazquez F, Byakhow M, Lichinitser M, Climent MA, Ciruelos E, Ojeda B, Mansutti M, Bozhok A, Baronio R, Feyereislova A, Barton C, Valagussa P, Baselga J. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet. 2010 Jan 30;375(9712):377-84. [https://doi.org/10.1016/S0140-6736(09)61964-4 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20113825/ PubMed] ISRCTN86043495 | ||
+ | ## '''Update:''' Gianni L, Eiermann W, Semiglazov V, Lluch A, Tjulandin S, Zambetti M, Moliterni A, Vazquez F, Byakhov MJ, Lichinitser M, Climent MA, Ciruelos E, Ojeda B, Mansutti M, Bozhok A, Magazzù D, Heinzmann D, Steinseifer J, Valagussa P, Baselga J. Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH): follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet Oncol. 2014 May;15(6):640-7. Epub 2014 Mar 20. Erratum in: Lancet Oncol. 2018 Dec;19(12):e667. [https://doi.org/10.1016/S1470-2045(14)70080-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24657003/ PubMed] | ||
+ | # '''NeoALTTO:''' Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. [https://doi.org/10.1016/S0140-6736(11)61847-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705192/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22257673/ PubMed] [https://clinicaltrials.gov/study/NCT00553358 NCT00553358] | ||
+ | ## '''Update:''' de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. Epub 2014 Aug 14. [https://doi.org/10.1016/S1470-2045(14)70320-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25130998/ PubMed] | ||
+ | ## '''Update:''' Huober J, Holmes E, Baselga J, de Azambuja E, Untch M, Fumagalli D, Sarp S, Lang I, Smith I, Boyle F, Xu B, Lecocq C, Wildiers H, Jouannaud C, Hackman J, Dasappa L, Ciruelos E, Toral Pena JC, Adamchuk H, Hickish T, de la Pena L, Jackisch C, Gelber RD, Piccart-Gebhart M, Di Cosimo S. Survival outcomes of the NeoALTTO study (BIG 1-06): updated results of a randomised multicenter phase III neoadjuvant clinical trial in patients with HER2-positive primary breast cancer. Eur J Cancer. 2019 Sep;118:169-177. Epub 2019 Aug 1. [https://doi.org/10.1016/j.ejca.2019.04.038 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31377477/ PubMed] | ||
+ | # '''CALGB 40101:''' Shulman LN, Cirrincione CT, Berry DA, Becker HP, Perez EA, O'Regan R, Martino S, Atkins JN, Mayer E, Schneider CJ, Kimmick G, Norton L, Muss H, Winer EP, Hudis C. Six Cycles of Doxorubicin and Cyclophosphamide or Paclitaxel Are Not Superior to Four Cycles As Adjuvant Chemotherapy for Breast Cancer in Women With Zero to Three Positive Axillary Nodes: Cancer and Leukemia Group B 40101. J Clin Oncol. 2012 Nov 20;30(33):4071-6. Epub 2012 Jul 23. [https://doi.org/10.1200/JCO.2011.40.6405 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://ascopubs.org/doi/suppl/10.1200/jco.2011.40.6405/suppl_file/Protocol.pdf link to study protocol PDF] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494835/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22826271/ PubMed] [https://clinicaltrials.gov/study/NCT00041119 NCT00041119] | ||
+ | ## '''Update:''' Shulman LN, Berry DA, Cirrincione CT, Becker HP, Perez EA, O'Regan R, Martino S, Shapiro CL, Schneider CJ, Kimmick G, Burstein HJ, Norton L, Muss H, Hudis CA, Winer EP. Comparison of doxorubicin and cyclophosphamide versus single-agent paclitaxel as adjuvant therapy for breast cancer in women with 0 to 3 positive axillary nodes: CALGB 40101 (Alliance). J Clin Oncol. 2014 Aug 1;32(22):2311-7. Epub 2014 Jun 16. [https://doi.org/10.1200/jco.2013.53.7142 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105484/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24934787/ PubMed] | ||
+ | # '''PHARE:''' Pivot X, Romieu G, Debled M, Pierga JY, Kerbrat P, Bachelot T, Lortholary A, Espié M, Fumoleau P, Serin D, Jacquin JP, Jouannaud C, Rios M, Abadie-Lacourtoisie S, Tubiana-Mathieu N, Cany L, Catala S, Khayat D, Pauporté I, Kramar A; PHARE trial investigators. 6 months versus 12 months of adjuvant trastuzumab for patients with HER2-positive early breast cancer (PHARE): a randomised phase 3 trial. Lancet Oncol. 2013 Jul;14(8):741-8. Epub 2013 Jun 11. [https://doi.org/10.1016/S1470-2045(13)70225-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23764181/ PubMed] [https://clinicaltrials.gov/study/NCT00381901 NCT00381901] | ||
+ | ## '''Update:''' Pivot X, Romieu G, Debled M, Pierga JY, Kerbrat P, Bachelot T, Lortholary A, Espié M, Fumoleau P, Serin D, Jacquin JP, Jouannaud C, Rios M, Abadie-Lacourtoisie S, Venat-Bouvet L, Cany L, Catala S, Khayat D, Gambotti L, Pauporté I, Faure-Mercier C, Paget-Bailly S, Henriques J, Grouin JM; PHARE trial investigators. 6 months versus 12 months of adjuvant trastuzumab in early breast cancer (PHARE): final analysis of a multicentre, open-label, phase 3 randomised trial. Lancet. 2019 Jun 29;393(10191):2591-2598. Epub 2019 Jun 6. [https://doi.org/10.1016/S0140-6736(19)30653-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31178155/ PubMed] | ||
+ | # '''ALTTO:''' Piccart-Gebhart M, Holmes E, Baselga J, de Azambuja E, Dueck AC, Viale G, Zujewski JA, Goldhirsch A, Armour A, Pritchard KI, McCullough AE, Dolci S, McFadden E, Holmes AP, Tonghua L, Eidtmann H, Dinh P, Di Cosimo S, Harbeck N, Tjulandin S, Im YH, Huang CS, Diéras V, Hillman DW, Wolff AC, Jackisch C, Lang I, Untch M, Smith I, Boyle F, Xu B, Gomez H, Suter T, Gelber RD, Perez EA. Adjuvant lapatinib and trastuzumab for early human epidermal growth factor receptor 2-positive breast cancer: results from the randomized phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial. J Clin Oncol. 2016 Apr 1;34(10):1034-42. Epub 2015 Nov 23. [https://doi.org/10.1200/JCO.2015.62.1797 link to original article] [https://ascopubs.org/doi/suppl/10.1200/JCO.2015.62.1797/suppl_file/protocol_2015.621797.pdf link to protocol] '''dosing details in supplement have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872016/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26598744/ PubMed] [https://clinicaltrials.gov/study/NCT00490139 NCT00490139] | ||
+ | ##'''Update:''' Moreno-Aspitia A, Holmes EM, Jackisch C, de Azambuja E, Boyle F, Hillman DW, Korde L, Fumagalli D, Izquierdo MA, McCullough AE, Wolff AC, Pritchard KI, Untch M, Guillaume S, Ewer MS, Shao Z, Sim SH, Aziz Z, Demetriou G, Mehta AO, Andersson M, Toi M, Lang I, Xu B, Smith IE, Barrios CH, Baselga J, Gelber RD, Piccart-Gebhart M; ALTTO Steering Committee and Investigators. Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D). Eur J Cancer. 2021 May;148:287-296. Epub 2021 Mar 23. [https://doi.org/10.1016/j.ejca.2021.01.053 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103014/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33765513/ PubMed] | ||
+ | # '''SB3-G31-BC:''' Pivot X, Bondarenko I, Nowecki Z, Dvorkin M, Trishkina E, Ahn JH, Vinnyk Y, Im SA, Sarosiek T, Chatterjee S, Wojtukiewicz MZ, Moiseyenko V, Shparyk Y, Bello M 3rd, Semiglazov V, Song S, Lim J. Phase III, randomized, double-blind study comparing the efficacy, safety, and immunogenicity of SB3 (trastuzumab biosimilar) and reference trastuzumab in patients treated with neoadjuvant therapy for human epidermal growth factor receptor 2-positive early breast cancer. J Clin Oncol. 2018 Apr 1;36(10):968-974. Epub 2018 Jan 26. [https://doi.org/10.1200/JCO.2017.74.0126 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/29373094/ PubMed] [https://clinicaltrials.gov/study/NCT02149524 NCT02149524] | ||
+ | # '''SOLD:''' Joensuu H, Fraser J, Wildiers H, Huovinen R, Auvinen P, Utriainen M, Nyandoto P, Villman KK, Halonen P, Granstam-Björneklett H, Lundgren L, Sailas L, Turpeenniemi-Hujanen T, Tanner M, Yachnin J, Ritchie D, Johansson O, Huttunen T, Neven P, Canney P, Harvey VJ, Kellokumpu-Lehtinen PL, Lindman H. Effect of adjuvant trastuzumab for a duration of 9 weeks vs 1 year with concomitant chemotherapy for early human epidermal growth factor receptor 2-positive breast cancer: the SOLD randomized clinical trial. JAMA Oncol. 2018 Sep 1;4(9):1199-1206. [https://doi.org/10.1001/jamaoncol.2018.1380 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6143012/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29852043/ PubMed] [https://clinicaltrials.gov/study/NCT00593697 NCT00593697] | ||
+ | # '''Short-HER:''' Conte P, Frassoldati A, Bisagni G, Brandes AA, Donadio M, Garrone O, Piacentini F, Cavanna L, Giotta F, Aieta M, Gebbia V, Molino A, Musolino A, Ferro A, Maltoni R, Danese S, Zamagni C, Rimanti A, Cagossi K, Russo A, Pronzato P, Giovanardi F, Moretti G, Lombardo L, Schirone A, Beano A, Amaducci L, Bajardi EA, Vicini R, Balduzzi S, D'Amico R, Guarneri V; Reader study level-I and level-II Groups. Nine weeks versus 1 year adjuvant trastuzumab in combination with chemotherapy: final results of the phase III randomized Short-HER study. Ann Oncol. 2018 Dec 1;29(12):2328-2333. [https://doi.org/10.1093/annonc/mdy414 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/30219886/ PubMed] [https://clinicaltrials.gov/study/NCT00629278 NCT00629278] | ||
+ | ##'''Update:''' Conte P, Bisagni G, Piacentini F, Sarti S, Minichillo S, Anselmi E, Aieta M, Gebbia V, Schirone A, Musolino A, Garrone O, Beano A, Rimanti A, Giotta F, Turletti A, Miglietta F, Dieci MV, Vicini R, Balduzzi S, D'Amico R, Guarneri V. Nine-Week Versus One-Year Trastuzumab for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: 10-Year Update of the ShortHER Phase III Randomized Trial. J Clin Oncol. 2023 Nov 10;41(32):4976-4981. Epub 2023 Sep 25. [https://doi.org/10.1200/jco.23.00790 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10642895/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/37748109/ PubMed] | ||
+ | # '''KATHERINE:''' von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M, Wolmark N, Rastogi P, Schneeweiss A, Redondo A, Fischer HH, Jacot W, Conlin AK, Arce-Salinas C, Wapnir IL, Jackisch C, DiGiovanna MP, Fasching PA, Crown JP, Wülfing P, Shao Z, Rota Caremoli E, Wu H, Lam LH, Tesarowski D, Smitt M, Douthwaite H, Singel SM, Geyer CE Jr; KATHERINE Investigators. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med. 2019 Feb 14;380(7):617-628. Epub 2018 Dec 5. [https://doi.org/10.1056/NEJMoa1814017 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/30516102/ PubMed] [https://clinicaltrials.gov/study/NCT01772472 NCT01772472] | ||
+ | # '''PERSEPHONE:''' Earl HM, Hiller L, Vallier AL, Loi S, McAdam K, Hughes-Davies L, Harnett AN, Ah-See ML, Simcock R, Rea D, Raj S, Woodings P, Harries M, Howe D, Raynes K, Higgins HB, Wilcox M, Plummer C, Mansi J, Gounaris I, Mahler-Araujo B, Provenzano E, Chhabra A, Abraham JE, Caldas C, Hall PS, McCabe C, Hulme C, Miles D, Wardley AM, Cameron DA, Dunn JA; PERSEPHONE Steering Committee and Trial Investigators. 6 versus 12 months of adjuvant trastuzumab for HER2-positive early breast cancer (PERSEPHONE): 4-year disease-free survival results of a randomised phase 3 non-inferiority trial. Lancet. 2019 Jun 29;393(10191):2599-2612. Epub 2019 Jun 6. [https://doi.org/10.1016/S0140-6736(19)30650-6 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615016/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31178152/ PubMed] [https://clinicaltrials.gov/study/NCT00712140 NCT00712140] | ||
+ | # '''RESPECT:''' Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. [https://doi.org/10.1200/jco.20.00184 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/32936713/ PubMed] [https://clinicaltrials.gov/study/NCT01104935 NCT01104935] | ||
− | ==== | + | ==Trastuzumab and hyaluronidase monotherapy {{#subobject:e972d5|Regimen=1}}== |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #1, 6 mos {{#subobject:0dd6c6|Variant=1}}=== | |
− | ===Regimen # | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | {| | + | !style="width: 20%"|Study |
− | | | + | !style="width: 20%"|Dates of enrollment |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | | | + | !style="width: 20%"|Comparator |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615016/ Earl et al. 2019 (PERSEPHONE)] |
− | |style="background-color:# | + | |2007-2015 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (E-de-esc) |
− | |style="background-color:# | + | |[[#Trastuzumab_monotherapy_2|Trastuzumab]] x 12 mo |
+ | | style="background-color:#eeee01" |Non-inferior DFS (primary endpoint)<br>DFS48: 89.4% vs 89.8%<br>(HR 1.07, 90% CI 0.93-1.24) | ||
|- | |- | ||
− | | | + | |} |
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
− | | | + | ====Preceding treatment==== |
− | |style=" | + | *Not explicitly specified (pragmatic trial) |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab and hyaluronidase (Herceptin Hylecta)]] 600 mg/10,000 units SC once on day 1 | ||
+ | '''21-day cycle for 9 cycles (6 months)''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, 12 mos {{#subobject:0cc6c6|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | | | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615016/ Earl et al. 2019 (PERSEPHONE)] |
− | + | |2007-2015 | |
− | + | |style="background-color:#1a9851"|Phase 3 (C) | |
− | + | |[[#Trastuzumab_monotherapy_2|Trastuzumab]] x 6 mo | |
− | + | | style="background-color:#eeee01" |Non-inferior DFS | |
− | |||
− | |||
− | |||
− | |||
− | | | ||
− | |[[ | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6143012/ Joensuu et al. 2018 (SOLD)] |
− | |style="background-color:# | + | |2008-2014 |
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[Breast_cancer,_HER2-positive_-_null_regimens#Observation|No further treatment]] | ||
+ | |style="background-color:#ffffbf"|Inconclusive whether non-inferior DFS | ||
|- | |- | ||
|} | |} | ||
− | ==== | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | *[[ | + | ====Preceding treatment==== |
− | *[[Trastuzumab (Herceptin)]] | + | *SOLD: [[Surgery#Breast_cancer_surgery|Surgery]], then adjuvant [[#TH-FEC_.28Docetaxel.29|TH-FEC]] or [[#TH-FEC_.28Docetaxel.2C_SC_Trastuzumab.29|TH-FEC (SC)]] |
− | + | *PERSEPHONE: Not explicitly specified (pragmatic trial) | |
− | ''' | + | </div> |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab and hyaluronidase (Herceptin Hylecta)]] 600 mg/10,000 units SC once on day 1 | ||
+ | '''21-day cycle for 18 cycles (1 year)''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # | + | # '''SOLD:''' Joensuu H, Fraser J, Wildiers H, Huovinen R, Auvinen P, Utriainen M, Nyandoto P, Villman KK, Halonen P, Granstam-Björneklett H, Lundgren L, Sailas L, Turpeenniemi-Hujanen T, Tanner M, Yachnin J, Ritchie D, Johansson O, Huttunen T, Neven P, Canney P, Harvey VJ, Kellokumpu-Lehtinen PL, Lindman H. Effect of adjuvant trastuzumab for a duration of 9 weeks vs 1 year with concomitant chemotherapy for early human epidermal growth factor receptor 2-positive breast cancer: the SOLD randomized clinical trial. JAMA Oncol. 2018 Sep 1;4(9):1199-1206. [https://doi.org/10.1001/jamaoncol.2018.1380 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6143012/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29852043/ PubMed] [https://clinicaltrials.gov/study/NCT00593697 NCT00593697] |
− | + | # '''PERSEPHONE:''' Earl HM, Hiller L, Vallier AL, Loi S, McAdam K, Hughes-Davies L, Harnett AN, Ah-See ML, Simcock R, Rea D, Raj S, Woodings P, Harries M, Howe D, Raynes K, Higgins HB, Wilcox M, Plummer C, Mansi J, Gounaris I, Mahler-Araujo B, Provenzano E, Chhabra A, Abraham JE, Caldas C, Hall PS, McCabe C, Hulme C, Miles D, Wardley AM, Cameron DA, Dunn JA; PERSEPHONE Steering Committee and Trial Investigators. 6 versus 12 months of adjuvant trastuzumab for HER2-positive early breast cancer (PERSEPHONE): 4-year disease-free survival results of a randomised phase 3 non-inferiority trial. Lancet. 2019 Jun 29;393(10191):2599-2612. Epub 2019 Jun 6. [https://doi.org/10.1016/S0140-6736(19)30650-6 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615016/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31178152/ PubMed] [https://clinicaltrials.gov/study/NCT00712140 NCT00712140] | |
− | + | ==Trastuzumab emtansine monotherapy {{#subobject:d150e0|Regimen=1}}== | |
− | + | T-DM1: '''<u>T</u>'''rastuzumab-'''<u>DM1</u>''' (Trastuzumab emtansine) | |
− | + | ===Example orders=== | |
− | + | *[[Example orders for trastuzumab emtansine (Kadcyla) in breast cancer]] | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen {{#subobject:d31a82|Variant=1}}=== | |
− | + | {| class="wikitable" style="color:white; background-color:#404040" | |
− | == | + | |<small>'''FDA-recommended dose'''</small> |
− | {| class="wikitable" style=" | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | + | !style="width: 20%"|Study | |
− | + | !style="width: 20%"|Dates of enrollment | |
− | {| | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | | | + | !style="width: 20%"|Comparator |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | | | ||
− | |[[Levels_of_Evidence# | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1056/NEJMoa1814017 von Minckwitz et al. 2018 (KATHERINE)] |
− | |style="background-color:# | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" |
− | |[ | + | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-338-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' |
− | |||
|- | |- | ||
− | | | + | |} --> |
− | |style="background-color:# | + | |2013-2015 |
− | | | + | |style="background-color:#1a9851"|Phase 3 (E-RT-switch-ic) |
− | |style="background-color:# | + | |[[#Trastuzumab_monotherapy_2|Trastuzumab]] |
+ | |style="background-color:#1a9850"|Superior IDFS (primary endpoint)<br>IDFS36: 88% vs 77%<br>(HR 0.50, 95% CI 0.39-0.64) | ||
|- | |- | ||
|} | |} | ||
− | ==== | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | *[[ | + | ====Preceding treatment==== |
− | + | *[[Surgery#Breast_cancer_surgery|Surgery]], with residual invasive disease | |
− | *[[Trastuzumab ( | + | </div> |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | + | ====Antibody-drug conjugate therapy==== | |
+ | *[[Trastuzumab emtansine (Kadcyla)]] 3.6 mg/kg IV once on day 1 | ||
+ | '''21-day cycle for 14 cycles''' | ||
+ | </div></div> | ||
− | ''' | + | ===References=== |
+ | # '''KATHERINE:''' von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M, Wolmark N, Rastogi P, Schneeweiss A, Redondo A, Fischer HH, Jacot W, Conlin AK, Arce-Salinas C, Wapnir IL, Jackisch C, DiGiovanna MP, Fasching PA, Crown JP, Wülfing P, Shao Z, Rota Caremoli E, Wu H, Lam LH, Tesarowski D, Smitt M, Douthwaite H, Singel SM, Geyer CE Jr; KATHERINE Investigators. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med. 2019 Feb 14;380(7):617-628. Epub 2018 Dec 5. [https://doi.org/10.1056/NEJMoa1814017 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/30516102/ PubMed] [https://clinicaltrials.gov/study/NCT01772472 NCT01772472] | ||
+ | # '''CompassHER2 RD:''' [https://clinicaltrials.gov/study/NCT04457596 NCT04457596] | ||
− | ===Regimen # | + | =Metastatic or unresectable disease, first-line= |
− | {| | + | ''Note: some patients in these trials were pre-treated with non-HER2-targeted therapies.'' |
− | | | + | ==ACH {{#subobject:92e436|Regimen=1}}== |
− | |[[Levels_of_Evidence#Evidence| | + | ACH: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''erceptin (Trastuzumab) |
− | | | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | |[[Levels_of_Evidence# | + | ===Regimen {{#subobject:67e482|Variant=1}}=== |
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1056/NEJM200103153441101 Slamon et al. 2001] |
− | |style="background-color:# | + | |1995-1997 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (E-RT-esc) |
− | |style="background-color:# | + | |1a. [[Breast_cancer,_HER2-positive_-_historical#Cyclophosphamide_.26_Doxorubicin_.28AC.29|AC]]<br>1b. [[Breast_cancer,_HER2-positive_-_historical#Cyclophosphamide_.26_Epirubicin_.28EC.29|EC]] |
+ | |style="background-color:#91cf60"|Seems to have superior OS (secondary endpoint)<br>Median OS: 25.1 vs 20.3 mo<br><br>Superior TTP (co-primary endpoint)<br>Median TTP: 7.4 vs 4.6 mo | ||
|- | |- | ||
|} | |} | ||
− | ''This | + | ''Note: This is not commonly used; here for reference purposes only.'' |
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *Slamon et al. 2001: No previous anthracycline exposure | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[ | + | *[[Doxorubicin (Adriamycin)]] 60 mg/mg<sup>2</sup> IV once on day 1 |
− | + | *[[Cyclophosphamide (Cytoxan)]] 600 mg/mg<sup>2</sup> IV once on day 1 | |
− | * | + | ====Targeted therapy==== |
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle 1: | + | **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15 |
− | **Cycle 2 onwards: | + | **Cycle 2 onwards: 2 mg/kg IV once per day on days 1, 8, 15 |
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001 Mar 15;344(11):783-92. [https://doi.org/10.1056/NEJM200103153441101 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11248153/ PubMed] | ||
− | + | ==Capecitabine, Bevacizumab, Trastuzumab {{#subobject:b68b8e|Regimen=1}}== | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen {{#subobject:d76d98|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 80%; text-align:center;" | |
− | + | !style="width: 25%"|Study | |
− | + | !style="width: 25%"|Dates of enrollment | |
− | + | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
− | ===Regimen | + | !style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]] |
− | {| | ||
− | | | ||
− | |[[Levels_of_Evidence#Evidence| | ||
− | |||
− | |[[Levels_of_Evidence#Efficacy| | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3336828/ Martín et al. 2012 (MO21926)] |
− | |style="background-color:# | + | |2008-2010 |
− | + | |style="background-color:#91cf61"|Phase 2 | |
− | |style="background-color:# | + | |style="background-color:#bababa"|ORR: 73% (95% CI 62-82) |
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | ==== | + | ====Chemotherapy==== |
− | *[[ | + | *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14 |
+ | ====Targeted therapy==== | ||
+ | *[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1 | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle 1: | + | **Cycle 1: 8 mg/kg IV once on day 1 |
− | ** | + | **Cycle 2 onwards: 6 mg/kg IV once on day 1 |
− | + | '''21-day cycles''' | |
− | + | </div></div> | |
− | + | ===References=== | |
− | + | # '''MO21926:''' Martín M, Makhson A, Gligorov J, Lichinitser M, Lluch A, Semiglazov V, Scotto N, Mitchell L, Tjulandin S. Phase II study of bevacizumab in combination with trastuzumab and capecitabine as first-line treatment for HER-2-positive locally recurrent or metastatic breast cancer. Oncologist. 2012;17(4):469-75. Epub 2012 Mar 30. [https://doi.org/10.1634/theoncologist.2011-0344 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3336828/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22467666/ PubMed] [https://clinicaltrials.gov/study/NCT00811135 NCT00811135] | |
− | + | ==Capecitabine & Lapatinib {{#subobject:800fde|Regimen=1}}== | |
− | '''21-day | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | + | ===Regimen {{#subobject:653bef|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | + | !style="width: 20%"|Study | |
− | + | !style="width: 20%"|Dates of enrollment | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
− | + | !style="width: 20%"|Comparator | |
− | ''' | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | + | |- | |
− | ===Regimen | + | |[https://doi.org/10.1200/JCO.2014.57.1794 Pivot et al. 2015 (CEREBEL)] |
− | {| | + | |2009-2012 |
− | | | + | |style="background-color:#1a9851"|Phase 3 (E-switch-ic) |
− | |[[Levels_of_Evidence#Evidence| | + | |[[#Capecitabine_.26_Trastuzumab_.28XH.29|Capecitabine & Trastuzumab]] |
− | | | + | |style="background-color:#ffffbf"|Did not meet primary endpoint of CNS metastases as first site of relapse |
− | |[[Levels_of_Evidence#Efficacy| | ||
|- | |- | ||
− | |[ | + | |} |
− | |style="background-color:# | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | |style=" | + | ====Chemotherapy==== |
− | |style=" | + | *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14 |
+ | ====Targeted therapy==== | ||
+ | *[[Lapatinib (Tykerb)]] 1250 mg PO once per day on days 1 to 21 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''CEREBEL:''' Pivot X, Manikhas A, Żurawski B, Chmielowska E, Karaszewska B, Allerton R, Chan S, Fabi A, Bidoli P, Gori S, Ciruelos E, Dank M, Hornyak L, Margolin S, Nusch A, Parikh R, Nagi F, DeSilvio M, Santillana S, Swaby RF, Semiglazov V. CEREBEL (EGF111438): A phase III, randomized, open-label study of lapatinib plus capecitabine versus trastuzumab plus capecitabine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2015 May 10;33(14):1564-73. Epub 2015 Jan 20. [https://doi.org/10.1200/JCO.2014.57.1794 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25605838/ PubMed] [https://clinicaltrials.gov/study/NCT00820222 NCT00820222] | ||
+ | ==Capecitabine & Trastuzumab (XH) {{#subobject:677608|Regimen=1}}== | ||
+ | XH: '''<u>X</u>'''eloda (Capecitabine) & '''<u>H</u>'''erceptin (Trastuzumab) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:e14cab|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/JCO.2014.57.1794 Pivot et al. 2015 (CEREBEL)] |
− | |style="background-color:# | + | |2009-2012 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |[[#Capecitabine_.26_Lapatinib|Capecitabine & Lapatanib]] |
+ | |style="background-color:#ffffbf"|Did not meet primary endpoint of CNS metastases as first site of relapse | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[ | + | *[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO twice per day on days 1 to 14 |
− | *[[Trastuzumab (Herceptin)]] | + | ====Targeted therapy==== |
− | **Cycle 1: | + | *[[Trastuzumab (Herceptin)]] as follows: |
− | **Cycle 2 onwards: | + | **Cycle 1: 8 mg/kg IV once on day 1 |
− | + | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | |
− | === | + | '''21-day cycles''' |
− | + | </div></div> | |
− | + | ===References=== | |
− | ''' | + | # '''CEREBEL:''' Pivot X, Manikhas A, Żurawski B, Chmielowska E, Karaszewska B, Allerton R, Chan S, Fabi A, Bidoli P, Gori S, Ciruelos E, Dank M, Hornyak L, Margolin S, Nusch A, Parikh R, Nagi F, DeSilvio M, Santillana S, Swaby RF, Semiglazov V. CEREBEL (EGF111438): A phase III, randomized, open-label study of lapatinib plus capecitabine versus trastuzumab plus capecitabine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2015 May 10;33(14):1564-73. Epub 2015 Jan 20. [https://doi.org/10.1200/JCO.2014.57.1794 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25605838/ PubMed] [https://clinicaltrials.gov/study/NCT00820222 NCT00820222] |
− | ===Regimen # | + | ==Carboplatin & Paclitaxel (CP) & Trastuzumab {{#subobject:dc581d|Regimen=1}}== |
− | {| | + | TPC: '''<u>T</u>'''rastuzumab, '''<u>P</u>'''aclitaxel, '''<u>C</u>'''arboplatin |
− | | | + | <br>TCH: '''<u>T</u>'''axol (Paclitaxel), '''<u>C</u>'''arboplatin, '''<u>H</u>'''erceptin (Trastuzumab) |
− | |[[Levels_of_Evidence#Evidence| | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | + | ===Regimen variant #1, weekly {{#subobject:deacc5|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" | |
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.3816/CBC.2005.n.047 Perez et al. 2005 (NCCTG 983252)] |
− | | | + | |1999-04 to 2003-07 |
− | + | | style="background-color:#91cf61" |Phase 2 | |
− | |style="background-color:# | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | ==== | + | ====Targeted therapy==== |
− | |||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
− | **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 | + | **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22 |
− | **Cycles 2 to 6: 2 mg/kg IV once per day on days 1, 8, 15 | + | **Cycles 2 to 6: 2 mg/kg IV once per day on days 1, 8, 15, 22 |
− | + | ====Chemotherapy==== | |
− | ==== | + | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 |
− | * | + | *[[Carboplatin (Paraplatin)]] AUC 2 IV once per day on days 1, 8, 15 |
− | + | '''28-day cycle for 6 cycles''' | |
− | ''' | + | </div> |
− | + | <div class="toccolours" style="background-color:#cbd5e7"> | |
− | + | ====Subsequent treatment==== | |
− | + | *[[#Trastuzumab_monotherapy_4|Trastuzumab]] maintenance (weekly) | |
− | ==== | + | </div></div><br> |
− | *[[Trastuzumab ( | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | + | ===Regimen variant #2, weekly T, q3wk PC {{#subobject:573aed|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | + | !style="width: 20%"|Study | |
− | === | + | !style="width: 20%"|Dates of enrollment |
− | # | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | + | !style="width: 20%"|Comparator | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | |
− | # | + | |- |
− | + | |[https://doi.org/10.1200/jco.2005.04.1764 Robert et al. 2006] | |
− | + | |1998-2002 | |
− | # | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
− | + | |[[#Paclitaxel_.26_Trastuzumab_.28TH.29_3|TP]] | |
− | # | + | | style="background-color:#1a9850" |Superior PFS (secondary endpoint)<br>Median PFS: 10.7 vs 7.1 mo<br>(HR 0.66, 95% CI 0.59-0.73)<br><br>Seems to have superior ORR (primary endpoint) |
− | < | ||
− | |||
− | |||
− | |||
− | |||
|- | |- | ||
− | |||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15 | ||
+ | **Cycle 2 onwards: 2 mg/kg IV once per day on days 1, 8, 15 | ||
+ | ====Chemotherapy==== | ||
+ | *[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 2 | ||
+ | *[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 2 | ||
+ | '''21-day cycle for at least 6 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[#Trastuzumab_monotherapy_4|Trastuzumab]] maintenance (weekly) | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
− | + | ===Regimen variant #3, q3wk {{#subobject:582fae|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" | |
− | ===Regimen {{#subobject: | + | !style="width: 33%"|Study |
− | {| | + | !style="width: 33%"|Dates of enrollment |
− | | | + | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | |[[Levels_of_Evidence#Evidence| | ||
− | |||
− | |||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.3816/CBC.2005.n.047 Perez et al. 2005 (NCCTG 983252)] |
− | | | + | |1999-04 to 2003-07 |
− | + | | style="background-color:#91cf61" |Phase 2 | |
− | |style="background-color:# | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycles 2 to 8: 6 mg/kg IV once on day 1 | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Docetaxel (Taxotere)]] as follows: | + | *[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV once on day 1 |
− | **Cycle 1: | + | *[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1 |
− | **Cycle 2 onwards: | + | '''21-day cycle for 8 cycles''' |
− | *[[Trastuzumab (Herceptin)]] as follows: | + | </div> |
− | **Cycle 1: | + | <div class="toccolours" style="background-color:#cbd5e7"> |
− | **Cycle 2 onwards: 6 mg/ | + | ====Subsequent treatment==== |
− | *[[ | + | *[[#Trastuzumab_monotherapy_4|Trastuzumab]] maintenance (q3wk) |
− | **Cycle 1: | + | </div></div> |
− | **Cycle 2 onwards: | + | ===References=== |
− | + | # '''NCCTG 983252:''' Perez EA, Suman VJ, Rowland KM, Ingle JN, Salim M, Loprinzi CL, Flynn PJ, Mailliard JA, Kardinal CG, Krook JE, Thrower AR, Visscher DW, Jenkins RB. Two concurrent phase II trials of paclitaxel/carboplatin/trastuzumab (weekly or every-3-week schedule) as first-line therapy in women with HER2-overexpressing metastatic breast cancer: NCCTG study 983252. Clin Breast Cancer. 2005 Dec;6(5):425-32. [https://doi.org/10.3816/CBC.2005.n.047 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16381626/ PubMed] | |
− | '''21-day cycle for at least 6 cycles, | + | # Robert N, Leyland-Jones B, Asmar L, Belt R, Ilegbodu D, Loesch D, Raju R, Valentine E, Sayre R, Cobleigh M, Albain K, McCullough C, Fuchs L, Slamon D. Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer. J Clin Oncol. 2006 Jun 20;24(18):2786-92. [https://doi.org/10.1200/jco.2005.04.1764 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16782917/ PubMed] |
+ | ==Docetaxel & Trastuzumab (TH) {{#subobject:c99645|Regimen=1}}== | ||
+ | TH: '''<u>T</u>'''axotere (Docetaxel) & '''<u>H</u>'''erceptin (Trastuzumab) | ||
+ | <br>HT: '''<u>H</u>'''erceptin (Trastuzumab) & '''<u>T</u>'''axotere (Docetaxel) | ||
+ | <br>H+D: '''<u>H</u>'''erceptin (Trastuzumab) & '''<u>D</u>'''ocetaxel | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, 35 mg/m<sup>2</sup> docetaxel, 3 out of 4 weeks {{#subobject:f2e79b|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2002.07.058 Esteva et al. 2002] | ||
+ | |Not reported | ||
+ | |style="background-color:#91cf61"|Phase 2 | ||
+ | |style="background-color:#d3d3d3"| | ||
+ | |style="background-color:#d3d3d3"| | ||
+ | |- | ||
+ | |[https://doi.org/10.1002/cncr.22885 Burstein et al. 2007 (TRAVIOTA)] | ||
+ | |2001-2003 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-switch-ic) | ||
+ | |[[#Vinorelbine_.26_Trastuzumab_.28VH.29_2|VH]] | ||
+ | |style="background-color:#fee08b"|Might have inferior TTP (secondary endpoint)<br>Median TTP: 6 vs 8.5 mo | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: Esteva et al. 2002 described the day before the start of a cycle as "day 0," which is not the typical convention, so day -1 is being used instead.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Docetaxel (Taxotere)]] 35 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15, '''given first''' | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] '''given second''' as follows: | ||
+ | **Cycle 1: 4 mg/kg IV over 90 minutes once on day -1, then 2 mg/kg IV over 30 minutes once per day on days 8 & 15 | ||
+ | **Cycle 2 onwards: 2 mg/kg IV over 30 minutes once per day on days 1, 8, 15 | ||
+ | ====Supportive therapy==== | ||
+ | *[[Dexamethasone (Decadron)]] 4 mg PO every 12 hours x 3 doses on cycles 1 & 2, starting the night prior to docetaxel. Patients who did not have "hypersensitivity reactions and no significant fluid retention during the first 8 weeks" received 4 mg PO twice per day on day 1 for at least the next two cycles. Patients who "remained free of fluid retention after 8 additional weeks" then received 4 mg PO once on day 1 prior to docetaxel in subsequent cycles. | ||
+ | '''28-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, 35 mg/m<sup>2</sup> docetaxel, 7 out of 8 weeks {{#subobject:f7a79b|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1002/cncr.22885 Burstein et al. 2007 (TRAVIOTA)] | ||
+ | |2001-2003 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-switch-ic) | ||
+ | |[[#Vinorelbine_.26_Trastuzumab_.28VH.29_2|VH]] | ||
+ | |style="background-color:#fee08b"|Might have inferior TTP (secondary endpoint)<br>Median TTP: 6 vs 8.5 mo | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Docetaxel (Taxotere)]] 35 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29, 36, 43 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15 | ||
+ | **Cycle 2 onwards: 2 mg/kg IV once per day on days 1, 8, 15 | ||
+ | '''8-week cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #3, 60 mg/m<sup>2</sup> q3wk docetaxel, weekly trastuzumab {{#subobject:8c2fd1|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1007/s10549-009-0498-7 Inoue et al. 2009 (JO17360)] | ||
+ | |2004-2008 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#Trastuzumab_monotherapy_2|H]] | ||
+ | |style="background-color:#91cf60"|Seems to have superior OS (co-primary endpoint)<br>Median OS: NYR vs NYR<br>(HR 0.37, 95% CI 0.14-0.97) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15 | ||
+ | **Cycle 2 onwards: 2 mg/kg IV once per day on days 1, 8, 15 | ||
+ | '''21-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #4, 75 mg/m<sup>2</sup> q3wk docetaxel, q3wk trastuzumab {{#subobject:d6d8da|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2012.44.9694 Hurvitz et al. 2013 (TDM4450g)] | ||
+ | |2008-2009 | ||
+ | |style="background-color:#1a9851"|Randomized Phase 2 (C) | ||
+ | |[[#Trastuzumab_emtansine_monotherapy_3|T-DM1]] | ||
+ | |style="background-color:#fc8d59"|Seems to have inferior PFS | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705202/ Baselga et al. 2011 (CLEOPATRA)] | ||
+ | |2008-2010 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#THP_.28Docetaxel.29_3|THP]] | ||
+ | |style="background-color:#d73027"|Inferior OS<sup>1</sup> | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.2014.56.9590 Gelmon et al. 2015 (NCIC-CTG MA.31)] | ||
+ | |2008-2011 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[Stub#Docetaxel_.26_Lapatinib_.28TL.29|TL (Docetaxel)]]<br>1b. [[#Lapatinib_.26_Paclitaxel_999|Lapatinib & Paclitaxel]] | ||
+ | | style="background-color:#1a9850" |Superior PFS (primary endpoint) | ||
+ | |- | ||
+ | |rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455677/ Perez et al. 2016 (MARIANNE)] | ||
+ | |rowspan=2|2010-2012 | ||
+ | |rowspan=2 style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1. [[#Trastuzumab_emtansine_monotherapy_3|T-DM1]] | ||
+ | |style="background-color:#eeee01"|Non-inferior PFS | ||
+ | |- | ||
+ | |2. [[#Pertuzumab_.26_T-DM1|Pertuzumab & T-DM1]] | ||
+ | |style="background-color:#eeee01"|Non-inferior PFS | ||
+ | |- | ||
+ | |[https://doi.org/10.1001/jama.2016.18305 Hugo et al. 2017 (HERITAGE)] | ||
+ | |2012-12-10 to 2015-08-05 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#Docetaxel_.26_Trastuzumab-dkst_.28TH.29_333|Docetaxel & Trastuzumab-dkst]]<br>1b. [[#Paclitaxel_.26_Trastuzumab-dkst_.28TH.29_333|Paclitaxel & Trastuzumab-dkst]] | ||
+ | |style="background-color:#eeee01"|Equivalent ORR24w (primary endpoint)<br>ORR24w: 64% vs 69.6% | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7320929/ Xu et al. 2020 (PUFFIN)] | ||
+ | |2016-09-13 to 2017-09-28 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#THP_.28Docetaxel.29_2|THP]] | ||
+ | | style="background-color:#d73027" |Inferior PFS<sup>2</sup> | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8084805/ Xu et al. 2021 (HLX02-BC01)] | ||
+ | |2016-11-11 to 2019-07-10 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#Docetaxel_.26_Trastuzumab-strf_.28TH.29_333|Docetaxel & Trastuzumab-strf]] | ||
+ | |style="background-color:#eeee01"|Equivalent ORR24w (primary endpoint)<br>ORR24w: 71.4% vs 71.3% | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10616786/ Ma et al. 2023 (PHILA)] | ||
+ | |2019-05-06 to 2022-01-17 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#Docetaxel_.26_Trastuzumab_.28TH.29_.26_Pyrotinib|TH & Pyrotinib]] | ||
+ | |style="background-color:#d73027"|Inferior PFS | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Reported efficacy for CLEOPATRA is based on the 2020 update.''<br> | ||
+ | ''<sup>2</sup>Reported efficacy for PUFFIN is based on the 2022 update.''<br> | ||
+ | ''Note: Dose of docetaxel in TDM4450g and MARIANNE was per investigator's discretion. CLEOPATRA has an unusual schedule with both medications being given on day 2 of cycle 1, due to this regimen being the control arm, in which patients in one arm received a placebo instead of pertuzumab on day 1. It is reasonable to assume that in practice, drugs in this regimen will be given on day 1 from the beginning.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV over 90 minutes once on day 2 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV over 30 minutes once on day 1 | ||
+ | '''21-day cycle for at least 6 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *CLEOPATRA, if it is decided to no longer administer docetaxel with this regimen: patients could continue to receive [[#Trastuzumab_monotherapy_4|trastuzumab]] maintenance | ||
+ | *NCIC-CTG MA.31: [[#Trastuzumab_monotherapy_4|Trastuzumab]] maintenance, after 8 cycles | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #5, 100 mg/m<sup>2</sup> q3wk docetaxel, weekly trastuzumab {{#subobject:31786c|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2005.04.173 Marty et al. 2005 (M77001)] | ||
+ | |2000-2002 | ||
+ | |style="background-color:#1a9851"|Randomized Phase 2 (E-esc) | ||
+ | |[[Breast_cancer,_HER2-positive_-_historical#Docetaxel_monotherapy|Docetaxel]] | ||
+ | |style="background-color:#91cf60"|Seems to have superior OS (secondary endpoint)<br><br>Superior ORR (primary endpoint) | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2010.28.6450 Valero et al. 2010 (BCIRG 007)] | ||
+ | |2001-2004 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#TCH_.28Docetaxel.29_2|TCH]] | ||
+ | |style="background-color:#ffffbf"|Did not meet primary endpoint of TTP | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 4 mg/kg IV over 90 minutes once on day 1, then 2 mg/kg IV over 30 minutes once per day on days 8 & 15 | ||
+ | **Cycles 2 to 8: 2 mg/kg IV over 30 minutes once per day on days 1, 8, 15 | ||
+ | ====Supportive therapy==== | ||
+ | *[[Dexamethasone (Decadron)]] 8 mg (or equivalent) PO twice per day x 6 doses, starting the night prior to docetaxel | ||
+ | *"Antiemetic premedication was mandatory" (no additional details given). | ||
+ | '''21-day cycle varying durations: 6 cycles (M77001); 8 cycles (BCIRG 007)''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *M77001: Patients could receive docetaxel beyond six cycles at the discretion of the investigator. Otherwise, patients proceeded to [[#Trastuzumab_monotherapy_4|trastuzumab]] maintenance. | ||
+ | *BCIRG 007: [[#Trastuzumab_monotherapy_4|Trastuzumab]] maintenance | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
− | + | ===Regimen variant #6, 100 mg/m<sup>2</sup> q3wk docetaxel, q3wk trastuzumab {{#subobject:a951ac|Variant=1}}=== | |
− | *[[ | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | *[[ | + | !style="width: 20%"|Study |
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.2010.30.8213 Andersson et al. 2010 (HERNATA)] | ||
+ | |2004-2008 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#Vinorelbine_.26_Trastuzumab_.28VH.29_2|VH]] | ||
+ | |style="background-color:#ffffbf"|Did not meet primary endpoint of TTP | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2012.44.7912 Gianni et al. 2013 (AVAREL)] | ||
+ | |2006-2010 | ||
+ | |style="background-color:#1a9851"|Randomized Phase 2 (C) | ||
+ | |[[Stub#BTH_.28Docetaxel.29|BTH]] | ||
+ | |style="background-color:#fee08b"|Might have inferior PFS | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2012.44.9694 Hurvitz et al. 2013 (TDM4450g)] | ||
+ | |2008-2009 | ||
+ | |style="background-color:#1a9851"|Randomized Phase 2 (C) | ||
+ | |[[#Trastuzumab_emtansine_monotherapy_3|T-DM1]] | ||
+ | |style="background-color:#fc8d59"|Seems to have inferior PFS | ||
+ | |- | ||
+ | |rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455677/ Perez et al. 2016 (MARIANNE)] | ||
+ | |rowspan=2|2010-2012 | ||
+ | |rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |1. [[#Trastuzumab_emtansine_monotherapy_3|T-DM1]] | ||
+ | |style="background-color:#eeee01"|Non-inferior PFS (primary endpoint) | ||
+ | |- | ||
+ | |2. [[#Pertuzumab_.26_T-DM1|Pertuzumab & T-DM1]] | ||
+ | |style="background-color:#eeee01"|Non-inferior PFS (primary endpoint) | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: In HERNATA, the day of docetaxel and trastuzumab were reversed in cycle 1. Dose of docetaxel in TDM4450g and MARIANNE was per investigator's discretion.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1 (see note) | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV over 90 minutes once on day 2 (see note) | ||
+ | **Cycle 2 onwards: 6 mg/kg IV over 30 minutes once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
− | '''21-day cycles, | + | ===References=== |
+ | # Esteva FJ, Valero V, Booser D, Guerra LT, Murray JL, Pusztai L, Cristofanilli M, Arun B, Esmaeli B, Fritsche HA, Sneige N, Smith TL, Hortobagyi GN. Phase II study of weekly docetaxel and trastuzumab for patients with HER-2-overexpressing metastatic breast cancer. J Clin Oncol. 2002 Apr 1;20(7):1800-8. [https://doi.org/10.1200/jco.2002.07.058 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11919237/ PubMed] | ||
+ | # '''M77001:''' Marty M, Cognetti F, Maraninchi D, Snyder R, Mauriac L, Tubiana-Hulin M, Chan S, Grimes D, Antón A, Lluch A, Kennedy J, O'Byrne K, Conte P, Green M, Ward C, Mayne K, Extra JM. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol. 2005 Jul 1;23(19):4265-74. Epub 2005 May 23. [https://doi.org/10.1200/jco.2005.04.173 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15911866/ PubMed] | ||
+ | # '''TRAVIOTA:''' Burstein HJ, Keshaviah A, Baron AD, Hart RD, Lambert-Falls R, Marcom PK, Gelman R, Winer EP. Trastuzumab plus vinorelbine or taxane chemotherapy for HER2-overexpressing metastatic breast cancer: the trastuzumab and vinorelbine or taxane study. Cancer. 2007 Sep 1;110(5):965-72. Epub 2007 Aug 20. [https://doi.org/10.1002/cncr.22885 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17614302/ PubMed] [https://clinicaltrials.gov/study/NCT00146549 NCT00146549] | ||
+ | # '''JO17360:''' Inoue K, Nakagami K, Mizutani M, Hozumi Y, Fujiwara Y, Masuda N, Tsukamoto F, Saito M, Miura S, Eguchi K, Shinkai T, Ando M, Watanabe T, Masuda N, Ohashi Y, Sano M, Noguchi S. Randomized phase III trial of trastuzumab monotherapy followed by trastuzumab plus docetaxel versus trastuzumab plus docetaxel as first-line therapy in patients with HER2-positive metastatic breast cancer: the JO17360 Trial Group. Breast Cancer Res Treat. 2010 Jan;119(1):127-36. Epub 2009 Aug 19. [https://doi.org/10.1007/s10549-009-0498-7 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19690954/ PubMed] | ||
+ | # '''BCIRG 007:''' Valero V, Forbes J, Pegram MD, Pienkowski T, Eiermann W, von Minckwitz G, Roche H, Martin M, Crown J, Mackey JR, Fumoleau P, Rolski J, Mrsic-Krmpotic Z, Jagiello-Gruszfeld A, Riva A, Buyse M, Taupin H, Sauter G, Press MF, Slamon DJ. Multicenter phase III randomized trial comparing docetaxel and trastuzumab with docetaxel, carboplatin, and trastuzumab as first-line chemotherapy for patients with HER2-gene-amplified metastatic breast cancer (BCIRG 007 study): two highly active therapeutic regimens. J Clin Oncol. 2011 Jan 10;29(2):149-56. Epub 2010 Nov 29. [https://doi.org/10.1200/jco.2010.28.6450 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21115860/ PubMed] [https://clinicaltrials.gov/study/NCT00047255 NCT00047255] | ||
+ | # '''HERNATA:''' Andersson M, Lidbrink E, Bjerre K, Wist E, Enevoldsen K, Jensen AB, Karlsson P, Tange UB, Sørensen PG, Møller S, Bergh J, Langkjer ST. Phase III randomized study comparing docetaxel plus trastuzumab with vinorelbine plus trastuzumab as first-line therapy of metastatic or locally advanced human epidermal growth factor receptor 2-positive breast cancer: the HERNATA study. J Clin Oncol. 2011 Jan 20;29(3):264-71. Epub 2010 Dec 13. [https://doi.org/10.1200/JCO.2010.30.8213 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21149659/ PubMed] [https://clinicaltrials.gov/study/NCT00430001 NCT00430001] | ||
+ | # '''CLEOPATRA:''' Baselga J, Cortés J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, Clark E, Benyunes MC, Ross G, Swain SM; CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012 Jan 12;366(2):109-19. Epub 2011 Dec 7. [https://doi.org/10.1056/NEJMoa1113216 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705202/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22149875/ PubMed] [https://clinicaltrials.gov/study/NCT00567190 NCT00567190] | ||
+ | ## '''Update:''' Swain SM, Kim SB, Cortés J, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Knott A, Clark E, Ross G, Benyunes MC, Baselga J. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2013 May;14(6):461-71. Epub 2013 Apr 18. [https://doi.org/10.1016/S1470-2045(13)70130-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076842/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23602601/ PubMed] | ||
+ | ##'''HRQoL analysis:''' Cortés J, Baselga J, Im YH, Im SA, Pivot X, Ross G, Clark E, Knott A, Swain SM. Health-related quality-of-life assessment in CLEOPATRA, a phase III study combining pertuzumab with trastuzumab and docetaxel in metastatic breast cancer. Ann Oncol. 2013 Oct;24(10):2630-2635. Epub 2013 Jul 17. [https://doi.org/10.1093/annonc/mdt274 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23868905/ PubMed] | ||
+ | ## '''Update:''' Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S, Clark E, Ross G, Benyunes MC, Cortés J; CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015 Feb 19;372(8):724-34. [https://doi.org/10.1056/NEJMoa1413513 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5584549/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25693012/ PubMed] | ||
+ | ## '''Update:''' Swain SM, Miles D, Kim SB, Im YH, Im SA, Semiglazov V, Ciruelos E, Schneeweiss A, Loi S, Monturus E, Clark E, Knott A, Restuccia E, Benyunes MC, Cortés J; CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020 Apr;21(4):519-530. Epub 2020 Mar 12. [https://doi.org/10.1016/s1470-2045(19)30863-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32171426/ PubMed] | ||
+ | <!-- Presented at the European Multidisciplinary Cancer Congress, Stockholm, Sweden, September 23-27, 2011, and the European Society of Medical Oncology Congress, Milan, Italy, October 8–12, 2010. --> | ||
+ | # '''TDM4450g:''' Hurvitz SA, Dirix L, Kocsis J, Bianchi GV, Lu J, Vinholes J, Guardino E, Song C, Tong B, Ng V, Chu YW, Perez EA. Phase II randomized study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2013 Mar 20;31(9):1157-63. Epub 2013 Feb 4. Erratum in: J Clin Oncol. 2013 Aug 10;31(23):2977. [https://doi.org/10.1200/jco.2012.44.9694 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23382472/ PubMed] [https://clinicaltrials.gov/study/NCT00679341 NCT00679341] | ||
+ | <!-- Presented in part at the San Antonio Breast Cancer Symposium, San Antonio, TX, December 6-11, 2011. --> | ||
+ | # '''AVAREL:''' Gianni L, Romieu GH, Lichinitser M, Serrano SV, Mansutti M, Pivot X, Mariani P, Andre F, Chan A, Lipatov O, Chan S, Wardley A, Greil R, Moore N, Prot S, Pallaud C, Semiglazov V. AVEREL: a randomized phase III trial evaluating bevacizumab in combination with docetaxel and trastuzumab as first-line therapy for HER2-positive locally recurrent/metastatic breast cancer. J Clin Oncol. 2013 May 10;31(14):1719-25. Epub 2013 Apr 8. [https://doi.org/10.1200/jco.2012.44.7912 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23569311/ PubMed] [https://clinicaltrials.gov/study/NCT00391092 NCT00391092] | ||
+ | # '''NCIC-CTG MA.31:''' Gelmon KA, Boyle FM, Kaufman B, Huntsman DG, Manikhas A, Di Leo A, Martin M, Schwartzberg LS, Lemieux J, Aparicio S, Shepherd LE, Dent S, Ellard SL, Tonkin K, Pritchard KI, Whelan TJ, Nomikos D, Nusch A, Coleman RE, Mukai H, Tjulandin S, Khasanov R, Rizel S, Connor AP, Santillana SL, Chapman JA, Parulekar WR. Lapatinib or trastuzumab plus taxane therapy for human epidermal growth factor receptor 2-positive advanced breast cancer: final results of NCIC-CTG MA.31. J Clin Oncol. 2015 May 10;33(14):1574-83. Epub 2015 Mar 16. [https://doi.org/10.1200/JCO.2014.56.9590 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25779558/ PubMed] [https://clinicaltrials.gov/study/NCT00667251 NCT00667251] | ||
+ | #'''HERITAGE:''' Rugo HS, Barve A, Waller CF, Hernandez-Bronchud M, Herson J, Yuan J, Sharma R, Baczkowski M, Kothekar M, Loganathan S, Manikhas A, Bondarenko I, Mukhametshina G, Nemsadze G, Parra JD, Abesamis-Tiambeng ML, Baramidze K, Akewanlop C, Vynnychenko I, Sriuranpong V, Mamillapalli G, Ray S, Yanez Ruiz EP, Pennella E; Heritage Study Investigators. Effect of a Proposed Trastuzumab Biosimilar Compared With Trastuzumab on Overall Response Rate in Patients With ERBB2 (HER2)-Positive Metastatic Breast Cancer: A Randomized Clinical Trial. JAMA. 2017 Jan 3;317(1):37-47. [https://doi.org/10.1001/jama.2016.18305 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27918780/ PubMed] [https://clinicaltrials.gov/study/NCT02472964 NCT02472964] | ||
+ | ##'''Update:''' Rugo HS, Pennella EJ, Gopalakrishnan U, Hernandez-Bronchud M, Herson J, Koch HF, Loganathan S, Deodhar S, Marwah A, Manikhas A, Bondarenko I, Mukhametshina G, Nemsadze G, Parra JD, Abesamis-Tiambeng MLT, Baramidze K, Akewanlop C, Vynnychenko I, Sriuranpong V, Mamillapalli G, Roy S, Yanez Ruiz EP, Barve A, Fuentes-Alburo A, Waller CF. Final overall survival analysis of the phase 3 HERITAGE study demonstrates equivalence of trastuzumab-dkst to trastuzumab in HER2-positive metastatic breast cancer. Breast Cancer Res Treat. 2021 Jul;188(2):369-377. Epub 2021 Jun 14. [https://doi.org/10.1007/s10549-021-06197-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8260531/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34125340/ PubMed] | ||
+ | # '''MARIANNE:''' Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, Martin M, Pienkowski T, Pivot X, Burris H 3rd, Petersen JA, Stanzel S, Strasak A, Patre M, Ellis P. Trastuzumab emtansine with or without pertuzumab versus trastuzumab plus taxane for human epidermal growth factor receptor 2-positive, advanced breast cancer: primary results from the phase III MARIANNE study. J Clin Oncol. 2017 Jan 10;35(2):141-148. Epub 2016 Nov 7. [https://doi.org/10.1200/JCO.2016.67.4887 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455677/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28056202/ PubMed] [https://clinicaltrials.gov/study/NCT01120184 NCT01120184] | ||
+ | ## '''Update:''' Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, Martin M, Pienkowski T, Pivot XB, Burris HA 3rd, Petersen JA, De Haas S, Hoersch S, Patre M, Ellis PA. Trastuzumab emtansine with or without pertuzumab versus trastuzumab with taxane for human epidermal growth factor receptor 2-positive advanced breast cancer: final results from MARIANNE. Cancer. 2019 Nov 15;125(22):3974-3984. Epub 2019 Jul 18. [https://doi.org/10.1002/cncr.32392 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31318460/ PubMed] | ||
+ | # '''PUFFIN:''' Xu B, Li W, Zhang Q, Shao Z, Li Q, Wang X, Li H, Sun T, Yin Y, Zheng H, Feng J, Zhang H, Lei G, Restuccia E. Pertuzumab, trastuzumab, and docetaxel for Chinese patients with previously untreated HER2-positive locally recurrent or metastatic breast cancer (PUFFIN): a phase III, randomized, double-blind, placebo-controlled study. Breast Cancer Res Treat. 2020 Aug;182(3):689-697. Epub 2020 Jun 20. [https://doi.org/10.1007/s10549-020-05728-w link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7320929/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/32564260/ PubMed] [https://clinicaltrials.gov/study/NCT02896855 NCT02896855] | ||
+ | ##'''Update:''' Xu B, Li W, Zhang Q, Li Q, Wang X, Li H, Sun T, Yin Y, Zheng H, Feng J, Zhu H, Siddiqui A, Macharia H, Knott A. Pertuzumab, trastuzumab, and docetaxel for Chinese patients with previously untreated HER2-positive locally recurrent or metastatic breast cancer (PUFFIN): final analysis of a phase III, randomized, double-blind, placebo-controlled study. Breast Cancer Res Treat. 2023 Feb;197(3):503-513. Epub 2022 Dec 4. [https://doi.org/10.1007/s10549-022-06775-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9883304/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36463547/ PubMed] | ||
+ | #'''HLX02-BC01:''' Xu B, Zhang Q, Sun T, Li W, Teng Y, Hu X, Bondarenko I, Adamchuk H, Zhang L, Trukhin D, Wang S, Zheng H, Tong Z, Shparyk Y, Wang Q; HLX02-BC01 Investigators. Efficacy, Safety, and Immunogenicity of HLX02 Compared with Reference Trastuzumab in Patients with Recurrent or Metastatic HER2-Positive Breast Cancer: A Randomized Phase III Equivalence Trial. BioDrugs. 2021 May;35(3):337-350. Epub 2021 Apr 7. [https://doi.org/10.1007/s40259-021-00475-w link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8084805/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33826080/ PubMed] [https://clinicaltrials.gov/study/NCT03084237 NCT03084237] | ||
+ | #'''PHILA:''' Ma F, Yan M, Li W, Ouyang Q, Tong Z, Teng Y, Wang Y, Wang S, Geng C, Luo T, Zhong J, Zhang Q, Liu Q, Zeng X, Sun T, Mo Q, Liu H, Cheng Y, Cheng J, Wang X, Nie J, Yang J, Wu X, Wang X, Li H, Ye C, Dong F, Wu S, Zhu X, Xu B; PHILA Investigators. Pyrotinib versus placebo in combination with trastuzumab and docetaxel as first line treatment in patients with HER2 positive metastatic breast cancer (PHILA): randomised, double blind, multicentre, phase 3 trial. BMJ. 2023 Oct 31;383:e076065. Erratum in: BMJ. 2023 Nov 16;383:p2665. [https://doi.org/10.1136/bmj-2023-076065 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10616786/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/37907210/ PubMed] [https://clinicaltrials.gov/study/NCT03863223 NCT03863223] | ||
+ | |||
+ | ==Docetaxel & Trastuzumab (TH) & Pyrotinib {{#subobject:cpy645|Regimen=1}}== | ||
+ | TH & Pyrotinib: '''<u>T</u>'''axotere (Docetaxel) & '''<u>H</u>'''erceptin (Trastuzumab) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:d6dhcw|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10616786/ Ma et al. 2023 (PHILA)] | ||
+ | |2019-05-06 to 2022-01-17 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |[[#Docetaxel_.26_Trastuzumab_.28TH.29_3|TH]] | ||
+ | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 24.3 vs 10.4 mo<br>(HR 0.41, 95% CI 0.32-0.53) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Pyrotinib (Irene)]] 400 mg PO once per day on days 1 to 21 | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 2 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycle for at least 6 cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''PHILA:''' Ma F, Yan M, Li W, Ouyang Q, Tong Z, Teng Y, Wang Y, Wang S, Geng C, Luo T, Zhong J, Zhang Q, Liu Q, Zeng X, Sun T, Mo Q, Liu H, Cheng Y, Cheng J, Wang X, Nie J, Yang J, Wu X, Wang X, Li H, Ye C, Dong F, Wu S, Zhu X, Xu B; PHILA Investigators. Pyrotinib versus placebo in combination with trastuzumab and docetaxel as first line treatment in patients with HER2 positive metastatic breast cancer (PHILA): randomised, double blind, multicentre, phase 3 trial. BMJ. 2023 Oct 31;383:e076065. Erratum in: BMJ. 2023 Nov 16;383:p2665. [https://doi.org/10.1136/bmj-2023-076065 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10616786/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/37907210/ PubMed] [https://clinicaltrials.gov/study/NCT03863223 NCT03863223] | ||
− | === | + | ==ECH {{#subobject:fd17f7|Regimen=1}}== |
− | + | ECH: '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''erceptin (Trastuzumab) | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen {{#subobject:959eb9|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | == | + | !style="width: 20%"|Study |
− | + | !style="width: 20%"|Dates of enrollment | |
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/NEJM200103153441101 Slamon et al. 2001] | ||
+ | |1995-1997 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-RT-esc) | ||
+ | |1a. [[Breast_cancer,_HER2-positive_-_historical#Cyclophosphamide_.26_Doxorubicin_.28AC.29|AC]]<br>1b. [[Breast_cancer,_HER2-positive_-_historical#Cyclophosphamide_.26_Epirubicin_.28EC.29|EC]] | ||
+ | |style="background-color:#91cf60"|Seems to have superior OS (secondary endpoint)<br>Median OS: 25.1 vs 20.3 mo<br><br>Superior TTP (co-primary endpoint)<br>Median TTP: 7.4 vs 4.6 mo | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: This is not commonly used; here for reference purposes only.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *Slamon et al. 2001: No previous anthracycline exposure | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Epirubicin (Ellence)]] 75 mg/mg<sup>2</sup> IV once on day 1 | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 600 mg/mg<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15 | ||
+ | **Cycle 2 onwards: 2 mg/kg IV once per day on days 1, 8, 15 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001 Mar 15;344(11):783-92. [https://doi.org/10.1056/NEJM200103153441101 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11248153/ PubMed] | ||
+ | |||
+ | ==Lapatinib & Paclitaxel (TL) {{#subobject:af5af0|Regimen=1}}== | ||
+ | TL: '''<u>T</u>'''axol (Paclitaxel) & '''<u>L</u>'''apatinib | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:6dda48|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.2011.40.5241 Guan et al. 2013 (EGF104535)] | ||
+ | |2006-2009 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |[[Breast_cancer,_HER2-positive_-_historical#Paclitaxel_monotherapy.2C_weekly_3|Paclitaxel]] | ||
+ | | style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 27.8 vs 20.5 mo<br>(HR 0.74, 95% CI 0.58-0.94) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Lapatinib (Tykerb)]] 1500 mg PO once per day on days 1 to 28 | ||
+ | '''28-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | <!-- Presented in part at the 33rd Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 8-12, 2010, and at the 36th Annual European Society of Medical Oncology Congress, Stockholm, Sweden, September 23-27, 2011. --> | ||
+ | # '''EGF104535:''' Guan Z, Xu B, DeSilvio ML, Shen Z, Arpornwirat W, Tong Z, Lorvidhaya V, Jiang Z, Yang J, Makhson A, Leung WL, Russo MW, Newstat B, Wang L, Chen G, Oliva C, Gomez H. Randomized trial of lapatinib versus placebo added to paclitaxel in the treatment of human epidermal growth factor receptor 2-overexpressing metastatic breast cancer. J Clin Oncol. 2013 Jun 1;31(16):1947-53. Epub 2013 Mar 18. [https://doi.org/10.1200/JCO.2011.40.5241 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23509322/ PubMed] [https://clinicaltrials.gov/study/NCT00281658 NCT00281658] | ||
+ | # '''NCIC-CTG MA.31:''' Gelmon KA, Boyle FM, Kaufman B, Huntsman DG, Manikhas A, Di Leo A, Martin M, Schwartzberg LS, Lemieux J, Aparicio S, Shepherd LE, Dent S, Ellard SL, Tonkin K, Pritchard KI, Whelan TJ, Nomikos D, Nusch A, Coleman RE, Mukai H, Tjulandin S, Khasanov R, Rizel S, Connor AP, Santillana SL, Chapman JA, Parulekar WR. Lapatinib or trastuzumab plus taxane therapy for human epidermal growth factor receptor 2-positive advanced breast cancer: final results of NCIC-CTG MA.31. J Clin Oncol. 2015 May 10;33(14):1574-83. Epub 2015 Mar 16. [https://doi.org/10.1200/JCO.2014.56.9590 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25779558/ PubMed] [https://clinicaltrials.gov/study/NCT00667251 NCT00667251] | ||
+ | ==Paclitaxel & Trastuzumab (TH) {{#subobject:aa22dd|Regimen=1}}== | ||
+ | TH: '''<u>T</u>'''axol (Paclitaxel), '''<u>H</u>'''erceptin (Trastuzumab) | ||
+ | <br>TP: '''<u>T</u>'''rastuzumab, '''<u>P</u>'''aclitaxel | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, weekly paclitaxel (80 mg/m<sup>2</sup>), weekly trastuzumab {{#subobject:2628d8|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2007.11.6699 Seidman et al. 2008 (CALGB 9840)] | ||
+ | |1998 to not reported | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-switch-ic) | ||
+ | |[[#Paclitaxel_.26_Trastuzumab_.28TH.29_3|TH]]; q3wk paclitaxel | ||
+ | |style="background-color:#1a9850"|Superior ORR (primary endpoint)<br>ORR: 42% vs 29%<br>(OR 1.75)<br><br>Superior OS (secondary endpoint)<br>Median OS: 24 vs 12 mo<br>(HR 0.78, 95% CI 0.65-0.94) | ||
+ | |- | ||
+ | |[https://doi.org/10.1002/cncr.22885 Burstein et al. 2007 (TRAVIOTA)] | ||
+ | |2001-2003 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-switch-ic) | ||
+ | |[[#Vinorelbine_.26_Trastuzumab_.28VH.29_2|VH]] | ||
+ | |style="background-color:#fee08b"|Might have inferior TTP (secondary endpoint) | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433508/ Baselga et al. 2014 (STM01-102)] | ||
+ | |2006-2009 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[Stub#MTP|MTP]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | ||
+ | |- | ||
+ | |rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455677/ Perez et al. 2016 (MARIANNE)] | ||
+ | |rowspan=2|2010-2012 | ||
+ | |rowspan=2 style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1. [[#Trastuzumab_emtansine_monotherapy_3|T-DM1]] | ||
+ | |style="background-color:#eeee01"|Non-inferior PFS | ||
+ | |- | ||
+ | |2. [[#Pertuzumab_.26_T-DM1|Pertuzumab & T-DM1]] | ||
+ | |style="background-color:#eeee01"|Non-inferior PFS | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: Different studies had different cycle lengths; this is the least divisible cycle length.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 4 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 2 mg/kg IV once on day 1 | ||
+ | '''7-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, weekly paclitaxel (80 mg/m<sup>2</sup>), q3wk trastuzumab {{#subobject:2q3kd8|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1001/jama.2016.18305 Hugo et al. 2017 (HERITAGE)] | ||
+ | |2012-12-10 to 2015-08-05 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#Docetaxel_.26_Trastuzumab-dkst_.28TH.29_333|Docetaxel & Trastuzumab-dkst]]<br>1b. [[#Paclitaxel_.26_Trastuzumab-dkst_.28TH.29_333|Paclitaxel & Trastuzumab-dkst]] | ||
+ | |style="background-color:#eeee01"|Equivalent ORR24w (primary endpoint)<br>ORR24w: 64% vs 69.6% | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV over 90 minutes once on day 1 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV over 60 minutes once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #3, weekly paclitaxel (90 mg/m<sup>2</sup>) {{#subobject:2628d8|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2001.19.10.2587 Seidman et al. 2001] | ||
+ | |Not reported | ||
+ | |style="background-color:#91cf61"|Phase 2 | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Paclitaxel (Taxol)]] 90 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 4 mg/kg IV once on day 0, then 2 mg/kg IV once per day on days 8, 15, 22 | ||
+ | **Cycle 2 onwards: 2 mg/kg IV once per day on days 1, 8, 15, 22 | ||
+ | '''28-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #4, paclitaxel 3 weeks out of 4, 6 cycles {{#subobject:812115|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.2014.56.9590 Gelmon et al. 2015 (NCIC-CTG MA.31)] | ||
+ | |2008-2011 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[Stub#Docetaxel_.26_Lapatinib_.28TL.29|TL (Docetaxel)]]<br>1b. [[#Lapatinib_.26_Paclitaxel_999|Lapatinib & Paclitaxel]] | ||
+ | | style="background-color:#1a9850" |Superior PFS (primary endpoint) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22 | ||
+ | **Cycles 2 to 6: 2 mg/kg IV once per day on days 1, 8, 15, 22 | ||
+ | '''28-day cycle for 6 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | |||
+ | ====Subsequent treatment==== | ||
+ | *[[#Trastuzumab_monotherapy_4|Trastuzumab]] maintenance | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #5, paclitaxel 3 weeks out of 4, indefinite {{#subobject:bf7990|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S1470-2045(15)00051-0 Hurvitz et al. 2015 (BOLERO-1)] | ||
+ | |2009-2012 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[Stub#Paclitaxel_.26_Trastuzumab_.28TH.29_.26_Everolimus|TH & Everolimus]] | ||
+ | |style="background-color:#ffffbf"|Did not meet primary endpoint of PFS | ||
+ | |- | ||
+ | |[https://doi.org/10.1001/jamaoncol.2016.0237 Awada et al. 2016 (NEfERT-T)] | ||
+ | |2009-2014 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[Stub#Neratinib_.26_Paclitaxel|Neratinib & Paclitaxel]] | ||
+ | |style="background-color:#ffffbf"|Did not meet primary endpoint of PFS | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6342915/ Pegram et al. 2018 (REFLECTIONS B327-02)] | ||
+ | |2014-04-04 to 2016-01-22 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#Paclitaxel_.26_Trastuzumab-bvzr_.28TH.29_333|Paclitaxel & Trastuzumab-bvzr]] | ||
+ | |style="background-color:#eeee01"|Equivalent ORR (primary endpoint)<br>ORR: 66.5% vs 62.5% | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22 | ||
+ | **Cycle 2 onwards: 2 mg/kg IV once per day on days 1, 8, 15, 22 | ||
+ | '''28-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | |||
+ | ===Regimen variant #6, q3wk paclitaxel, weekly trastuzumab {{#subobject:31e4b6|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/NEJM200103153441101 Slamon et al. 2001] | ||
+ | |1995-1997 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-RT-esc) | ||
+ | |[[Breast_cancer,_HER2-positive_-_historical#Paclitaxel_monotherapy.2C_q3wk|Paclitaxel]] | ||
+ | |style="background-color:#91cf60"|Seems to have superior OS (secondary endpoint)<br>Median OS: 25.1 vs 20.3 mo<br><br>Superior TTP (co-primary endpoint)<br>Median TTP: 7.4 vs 4.6 mo | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2005.04.1764 Robert et al. 2006] | ||
+ | |1998-2002 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Trastuzumab|TPC]] | ||
+ | | style="background-color:#d73027" |Inferior PFS | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2007.11.6699 Seidman et al. 2008 (CALGB 9840)] | ||
+ | |1998 to not reported | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#Paclitaxel_.26_Trastuzumab_.28TH.29_2|TH]]; weekly paclitaxel (80 mg/m<sup>2</sup>) | ||
+ | |style="background-color:#d73027"|Inferior OS | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *Slamon et al. 2001: Previous anthracycline exposure | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Paclitaxel (Taxol)]] as follows: | ||
+ | **Cycles 1 to 6: 175 mg/m<sup>2</sup> IV once on day 2 | ||
+ | **Cycle 7 onwards: continued at investigator's discretion | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15 | ||
+ | **Cycle 2 onwards: 2 mg/kg IV once per day on days 1, 8, 15 | ||
+ | '''21-day cycle for at least 6 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | |||
+ | ===Regimen variant #7, q3wk paclitaxel, q3wk trastuzumab {{#subobject:31q3b6|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7439710/ Alexeev et al. 2020 (BCD-022-02)] | ||
+ | |2012-10 to 2017-12 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#Paclitaxel_.26_Trastuzumab_.28TH.29_.28trastuzumab-hert.29_333|TH (biosimilar trastuzumab)]] | ||
+ | |style="background-color:#eeee01"|Equivalent ORR (primary endpoint)<br>ORR: 43.6% vs 49.6% | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Paclitaxel (Taxol)]] as follows: | ||
+ | **Cycles 1 to 6: 175 mg/m<sup>2</sup> IV once on day 2 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001 Mar 15;344(11):783-92. [https://doi.org/10.1056/NEJM200103153441101 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11248153/ PubMed] | ||
+ | # Seidman AD, Fornier MN, Esteva FJ, Tan L, Kaptain S, Bach A, Panageas KS, Arroyo C, Valero V, Currie V, Gilewski T, Theodoulou M, Moynahan ME, Moasser M, Sklarin N, Dickler M, D'Andrea G, Cristofanilli M, Rivera E, Hortobagyi GN, Norton L, Hudis CA. Weekly trastuzumab and paclitaxel therapy for metastatic breast cancer with analysis of efficacy by HER2 immunophenotype and gene amplification. J Clin Oncol. 2001 May 15;19(10):2587-95. [https://doi.org/10.1200/jco.2001.19.10.2587 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11352950/ PubMed] | ||
+ | # Robert N, Leyland-Jones B, Asmar L, Belt R, Ilegbodu D, Loesch D, Raju R, Valentine E, Sayre R, Cobleigh M, Albain K, McCullough C, Fuchs L, Slamon D. Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer. J Clin Oncol. 2006 Jun 20;24(18):2786-92. [https://doi.org/10.1200/jco.2005.04.1764 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16782917/ PubMed] | ||
+ | # '''TRAVIOTA:''' Burstein HJ, Keshaviah A, Baron AD, Hart RD, Lambert-Falls R, Marcom PK, Gelman R, Winer EP. Trastuzumab plus vinorelbine or taxane chemotherapy for HER2-overexpressing metastatic breast cancer: the trastuzumab and vinorelbine or taxane study. Cancer. 2007 Sep 1;110(5):965-72. Epub 2007 Aug 20. [https://doi.org/10.1002/cncr.22885 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17614302/ PubMed] [https://clinicaltrials.gov/study/NCT00146549 NCT00146549] | ||
+ | <!-- Presented at the 40th Annual Meeting of the American Society of Clinical Oncology, June 5-8, 2004, New Orleans, LA. --> | ||
+ | # '''CALGB 9840:''' Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom PK, Gipson G, Burstein H, Lake D, Shapiro CL, Ungaro P, Norton L, Winer E, Hudis C. Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol. 2008 Apr 1;26(10):1642-9. [https://doi.org/10.1200/jco.2007.11.6699 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18375893/ PubMed] [https://clinicaltrials.gov/study/NCT00003440 NCT00003440] | ||
+ | # '''STM01-102:''' Baselga J, Manikhas A, Cortés J, Llombart A, Roman L, Semiglazov VF, Byakhov M, Lokanatha D, Forenza S, Goldfarb RH, Matera J, Azarnia N, Hudis CA, Rozencweig M. Phase III trial of nonpegylated liposomal doxorubicin in combination with trastuzumab and paclitaxel in HER2-positive metastatic breast cancer. Ann Oncol. 2014 Mar;25(3):592-8. Epub 2014 Jan 8. [https://doi.org/10.1093/annonc/mdt543 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433508/ link to PMC article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24401928/ PubMed] [https://clinicaltrials.gov/study/NCT00294996 NCT00294996] | ||
+ | # '''NCIC-CTG MA.31:''' Gelmon KA, Boyle FM, Kaufman B, Huntsman DG, Manikhas A, Di Leo A, Martin M, Schwartzberg LS, Lemieux J, Aparicio S, Shepherd LE, Dent S, Ellard SL, Tonkin K, Pritchard KI, Whelan TJ, Nomikos D, Nusch A, Coleman RE, Mukai H, Tjulandin S, Khasanov R, Rizel S, Connor AP, Santillana SL, Chapman JA, Parulekar WR. Lapatinib or trastuzumab plus taxane therapy for human epidermal growth factor receptor 2-positive advanced breast cancer: final results of NCIC-CTG MA.31. J Clin Oncol. 2015 May 10;33(14):1574-83. Epub 2015 Mar 16. [https://doi.org/10.1200/JCO.2014.56.9590 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25779558/ PubMed] [https://clinicaltrials.gov/study/NCT00667251 NCT00667251] | ||
+ | # '''BOLERO-1:''' Hurvitz SA, Andre F, Jiang Z, Shao Z, Mano MS, Neciosup SP, Tseng LM, Zhang Q, Shen K, Liu D, Dreosti LM, Burris HA, Toi M, Buyse ME, Cabaribere D, Lindsay MA, Rao S, Pacaud LB, Taran T, Slamon D. Combination of everolimus with trastuzumab plus paclitaxel as first-line treatment for patients with HER2-positive advanced breast cancer (BOLERO-1): a phase 3, randomised, double-blind, multicentre trial. Lancet Oncol. 2015 Jul;16(7):816-29. Epub 2015 Jun 16. [https://doi.org/10.1016/S1470-2045(15)00051-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26092818/ PubMed] [https://clinicaltrials.gov/study/NCT00876395 NCT00876395] | ||
+ | # '''MARIANNE:''' Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, Martin M, Pienkowski T, Pivot X, Burris H 3rd, Petersen JA, Stanzel S, Strasak A, Patre M, Ellis P. Trastuzumab emtansine with or without pertuzumab versus trastuzumab plus taxane for human epidermal growth factor receptor 2-positive, advanced breast cancer: primary results from the phase III MARIANNE study. J Clin Oncol. 2017 Jan 10;35(2):141-148. Epub 2016 Nov 7. [https://doi.org/10.1200/JCO.2016.67.4887 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455677/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28056202/ PubMed] [https://clinicaltrials.gov/study/NCT01120184 NCT01120184] | ||
+ | ## '''Update:''' Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, Martin M, Pienkowski T, Pivot XB, Burris HA 3rd, Petersen JA, De Haas S, Hoersch S, Patre M, Ellis PA. Trastuzumab emtansine with or without pertuzumab versus trastuzumab with taxane for human epidermal growth factor receptor 2-positive advanced breast cancer: final results from MARIANNE. Cancer. 2019 Nov 15;125(22):3974-3984. Epub 2019 Jul 18. [https://doi.org/10.1002/cncr.32392 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31318460/ PubMed] | ||
+ | # '''NEfERT-T:''' Awada A, Colomer R, Inoue K, Bondarenko I, Badwe RA, Demetriou G, Lee SC, Mehta AO, Kim SB, Bachelot T, Goswami C, Deo S, Bose R, Wong A, Xu F, Yao B, Bryce R, Carey LA. neratinib plus paclitaxel vs trastuzumab plus paclitaxel in previously untreated metastatic ERBB2-positive breast cancer: The NEfERT-T randomized clinical trial. JAMA Oncol. 2016 Dec 1;2(12):1557-1564. [https://doi.org/10.1001/jamaoncol.2016.0237 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27078022/ PubMed] [https://clinicaltrials.gov/study/NCT00915018 NCT00915018] | ||
+ | #'''HERITAGE:''' Rugo HS, Barve A, Waller CF, Hernandez-Bronchud M, Herson J, Yuan J, Sharma R, Baczkowski M, Kothekar M, Loganathan S, Manikhas A, Bondarenko I, Mukhametshina G, Nemsadze G, Parra JD, Abesamis-Tiambeng ML, Baramidze K, Akewanlop C, Vynnychenko I, Sriuranpong V, Mamillapalli G, Ray S, Yanez Ruiz EP, Pennella E; Heritage Study Investigators. Effect of a Proposed Trastuzumab Biosimilar Compared With Trastuzumab on Overall Response Rate in Patients With ERBB2 (HER2)-Positive Metastatic Breast Cancer: A Randomized Clinical Trial. JAMA. 2017 Jan 3;317(1):37-47. [https://doi.org/10.1001/jama.2016.18305 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27918780/ PubMed] [https://clinicaltrials.gov/study/NCT02472964 NCT02472964] | ||
+ | ##'''Update:''' Rugo HS, Pennella EJ, Gopalakrishnan U, Hernandez-Bronchud M, Herson J, Koch HF, Loganathan S, Deodhar S, Marwah A, Manikhas A, Bondarenko I, Mukhametshina G, Nemsadze G, Parra JD, Abesamis-Tiambeng MLT, Baramidze K, Akewanlop C, Vynnychenko I, Sriuranpong V, Mamillapalli G, Roy S, Yanez Ruiz EP, Barve A, Fuentes-Alburo A, Waller CF. Final overall survival analysis of the phase 3 HERITAGE study demonstrates equivalence of trastuzumab-dkst to trastuzumab in HER2-positive metastatic breast cancer. Breast Cancer Res Treat. 2021 Jul;188(2):369-377. Epub 2021 Jun 14. [https://doi.org/10.1007/s10549-021-06197-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8260531/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34125340/ PubMed] | ||
+ | #'''REFLECTIONS B327-02:''' Pegram MD, Bondarenko I, Zorzetto MMC, Hingmire S, Iwase H, Krivorotko PV, Lee KS, Li RK, Pikiel J, Aggarwal R, Ewesuedo R, Freyman A, Li R, Vana A, Yin D, Zacharchuk C, Tan-Chiu E. PF-05280014 (a trastuzumab biosimilar) plus paclitaxel compared with reference trastuzumab plus paclitaxel for HER2-positive metastatic breast cancer: a randomised, double-blind study. Br J Cancer. 2019 Jan;120(2):172-182. Epub 2018 Dec 20. [https://doi.org/10.1038/s41416-018-0340-2 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6342915/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/30568294/ PubMed] [https://clinicaltrials.gov/study/NCT01989676 NCT01989676] | ||
+ | ##'''Update:''' Li RK, Tokunaga E, Adamchuk H, Vladimirov V, Yanez E, Lee KS, Bondarenko I, Vana A, Hilton F, Ishikawa T, Tajima K, Lipatov O. Long-Term Safety and Effectiveness of PF-05280014 (a Trastuzumab Biosimilar) Treatment in Patients with HER2-Positive Metastatic Breast Cancer: Updated Results of a Randomized, Double-Blind Study. BioDrugs. 2022 Jan;36(1):55-69. Epub 2022 Feb 8. [https://doi.org/10.1007/s40259-021-00513-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8847243/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35133617/ PubMed] | ||
+ | #'''BCD-022-02:''' Alexeev SM, Khorinko AV, Mukhametshina GZ, Shelepen KG, Burdaeva ON, Kulik SA, Satheesh CT, Srivastava K, Vikranth M, Kryukov F, Paltusova AN, Shustova MS, Ivanov RA. Randomized double-blind clinical trial comparing safety and efficacy of the biosimilar BCD-022 with reference trastuzumab. BMC Cancer. 2020 Aug 20;20(1):783. [https://doi.org/10.1186/s12885-020-07247-9 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7439710/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/32819305/ PubMed] [https://clinicaltrials.gov/study/NCT01764022 NCT01764022] | ||
+ | |||
+ | ==nab-Paclitaxel & Trastuzumab {{#subobject:fgh1bc|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:c8cg38|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/j.clbc.2011.03.007 Mirtsching et al. 2011] | ||
+ | |2005-2006 | ||
+ | | style="background-color:#91cf61" |Phase 2 | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 125 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 4 mg/kg IV over 90 minutes once on day 1, then 2 mg/kg IV over 30 minutes once per day on days 8, 15, 22 | ||
+ | **Cycle 2 onwards: 2 mg/kg IV over 30 minutes once per day on days 1, 8, 15, 22 | ||
+ | '''28-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # Mirtsching B, Cosgriff T, Harker G, Keaton M, Chidiac T, Min M. A phase II study of weekly nanoparticle albumin-bound paclitaxel with or without trastuzumab in metastatic breast cancer. Clin Breast Cancer. 2011 Apr;11(2):121-8. Epub 2011 Apr 11. [https://doi.org/10.1016/j.clbc.2011.03.007 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21569998/ PubMed] | ||
+ | ==Pertuzumab & T-DM1 {{#subobject:ffffbc|Regimen=1}}== | ||
+ | Pertuzumab & T-DM1: Pertuzumab & '''<u>T</u>'''rastuzumab-'''<u>DM1</u>''' (Trastuzumab emtansine) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:c8ce38|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455677/ Perez et al. 2016 (MARIANNE)] | ||
+ | |rowspan=2|2010-2012 | ||
+ | |rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |1. [[#Trastuzumab_emtansine_monotherapy_3|T-DM1]] | ||
+ | |style="background-color:#eeee01"|Non-inferior PFS (primary endpoint)<br>Median PFS: 15.2 vs 14.1 mo | ||
+ | |- | ||
+ | |2a. [[#Docetaxel_.26_Trastuzumab_.28TH.29_3|TH (Docetaxel)]]<br>2b. [[#Paclitaxel_.26_Trastuzumab_.28TH.29_3|TH (Paclitaxel)]] | ||
+ | |style="background-color:#eeee01"|Non-inferior PFS (primary endpoint)<br>Median PFS: 15.2 vs 13.7 mo | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Pertuzumab (Perjeta)]] as follows: | ||
+ | **Cycle 1: 840 mg IV once on day 1 | ||
+ | **Cycle 2 onwards: 420 mg IV once on day 1 | ||
+ | ====Antibody-drug conjugate therapy==== | ||
+ | *[[Trastuzumab emtansine (Kadcyla)]] 3.6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''MARIANNE:''' Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, Martin M, Pienkowski T, Pivot X, Burris H 3rd, Petersen JA, Stanzel S, Strasak A, Patre M, Ellis P. Trastuzumab emtansine with or without pertuzumab versus trastuzumab plus taxane for human epidermal growth factor receptor 2-positive, advanced breast cancer: primary results from the phase III MARIANNE study. J Clin Oncol. 2017 Jan 10;35(2):141-148. Epub 2016 Nov 7. [https://doi.org/10.1200/JCO.2016.67.4887 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455677/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28056202/ PubMed] [https://clinicaltrials.gov/study/NCT01120184 NCT01120184] | ||
+ | ## '''Update:''' Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, Martin M, Pienkowski T, Pivot XB, Burris HA 3rd, Petersen JA, De Haas S, Hoersch S, Patre M, Ellis PA. Trastuzumab emtansine with or without pertuzumab versus trastuzumab with taxane for human epidermal growth factor receptor 2-positive advanced breast cancer: final results from MARIANNE. Cancer. 2019 Nov 15;125(22):3974-3984. Epub 2019 Jul 18. [https://doi.org/10.1002/cncr.32392 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31318460/ PubMed] | ||
+ | ==TCH (Docetaxel) {{#subobject:cb6592|Regimen=1}}== | ||
+ | TCH: '''<u>T</u>'''axotere (Docetaxel), '''<u>C</u>'''arboplatin, '''<u>H</u>'''erceptin (Trastuzumab) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:570bd5|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2010.28.6450 Valero et al. 2011 (BCIRG 007)] | ||
+ | |2001-2004 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |[[#Docetaxel_.26_Trastuzumab_.28TH.29_3|TH]] | ||
+ | |style="background-color:#ffffbf"|Did not meet primary endpoint of TTP<br>Median TTP: 10.4 vs 11.1 mo<br>(HR 1.09, 95% CI 0.83-1.44) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15 | ||
+ | **Cycles 2 to 8: 2 mg/kg IV once per day on days 1, 8, 15 | ||
+ | '''21-day cycle for 8 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[#Trastuzumab_monotherapy_4|Trastuzumab]] maintenance | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''BCIRG 007:''' Valero V, Forbes J, Pegram MD, Pienkowski T, Eiermann W, von Minckwitz G, Roche H, Martin M, Crown J, Mackey JR, Fumoleau P, Rolski J, Mrsic-Krmpotic Z, Jagiello-Gruszfeld A, Riva A, Buyse M, Taupin H, Sauter G, Press MF, Slamon DJ. Multicenter phase III randomized trial comparing docetaxel and trastuzumab with docetaxel, carboplatin, and trastuzumab as first-line chemotherapy for patients with HER2-gene-amplified metastatic breast cancer (BCIRG 007 study): two highly active therapeutic regimens. J Clin Oncol. 2011 Jan 10;29(2):149-56. Epub 2010 Nov 29. [https://doi.org/10.1200/jco.2010.28.6450 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21115860/ PubMed] [https://clinicaltrials.gov/study/NCT00047255 NCT00047255] | ||
+ | |||
+ | |||
+ | |||
+ | ==THP (Docetaxel) {{#subobject:938b69|Regimen=1}}== | ||
+ | THP: '''<u>T</u>'''axotere (Docetaxel), '''<u>H</u>'''erceptin (Trastuzumab), '''<u>P</u>'''ertuzumab | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:37f3dc|Variant=1}}=== | ||
+ | {| class="wikitable" style="color:white; background-color:#404040" | ||
+ | |<small>'''FDA-recommended dose'''</small> | ||
+ | |- | ||
+ | |} | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705202/ Baselga et al. 2011 (CLEOPATRA)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-4-1 <span style="color:white;">ESMO-MCBS (4)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2008-2010 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-RT-esc) | ||
+ | |[[#Docetaxel_.26_Trastuzumab_.28TH.29_3|Docetaxel & Trastuzumab]] | ||
+ | |style="background-color:#1a9850"|Superior PFS (primary endpoint)<br>Median PFS: 18.5 vs 12.4 mo<br>(HR 0.62, 95% CI 0.51-0.75)<br><br>Superior OS<sup>1</sup> (secondary endpoint)<br>Median OS: 57.1 vs 40.8 mo<br>(HR 0.69, 95% CI 0.58-0.82) | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7320929/ Xu et al. 2020 (PUFFIN)] | ||
+ | |2016-09-13 to 2017-09-28 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |[[#Docetaxel_.26_Trastuzumab_.28TH.29_3|Docetaxel & Trastuzumab]] | ||
+ | | style="background-color:#1a9850" |Superior PFS<sup>2</sup> (primary endpoint)<br>Median PFS: 16.5 vs 12.5 mo<br>(HR 0.60, 95% CI 0.45-0.81)<br><br>Might have superior OS<sup>2</sup> (secondary endpoint)<br>Median OS: NYR vs NYR<br>(HR 0.68, 95% CI 0.45-1.03) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Reported efficacy for CLEOPATRA is based on the 2020 update.''<br> | ||
+ | ''<sup>2</sup>Reported efficacy for PUFFIN is based on the 2022 update.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Docetaxel (Taxotere)]] '''given third''' as follows: | ||
+ | **Cycle 1: 75 mg/m<sup>2</sup> IV once on day 2 | ||
+ | **Cycle 2 onwards: 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV over 90 minutes once on day 2 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV over 30 to 90 minutes once on day 1 | ||
+ | *[[Pertuzumab (Perjeta)]] as follows: | ||
+ | **Cycle 1: 840 mg IV over 60 minutes once on day 1 | ||
+ | **Cycle 2 onwards: 420 mg IV over 30 to 60 minutes once on day 1 | ||
+ | '''21-day cycle for at least 6 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *CLEOPATRA, if it is decided to no longer administer docetaxel: patients could continue to receive [[#Pertuzumab_.26_Trastuzumab_2|pertuzumab & trastuzumab]] maintenance. | ||
+ | </div></div> | ||
+ | |||
+ | ===References=== | ||
+ | # '''CLEOPATRA:''' Baselga J, Cortés J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, Clark E, Benyunes MC, Ross G, Swain SM; CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012 Jan 12;366(2):109-19. Epub 2011 Dec 7. [https://doi.org/10.1056/NEJMoa1113216 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705202/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22149875/ PubMed] [https://clinicaltrials.gov/study/NCT00567190 NCT00567190] | ||
+ | ## '''Update:''' Swain SM, Kim SB, Cortés J, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Knott A, Clark E, Ross G, Benyunes MC, Baselga J. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2013 May;14(6):461-71. Epub 2013 Apr 18. [https://doi.org/10.1016/S1470-2045(13)70130-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076842/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23602601/ PubMed] | ||
+ | ##'''HRQoL analysis:''' Cortés J, Baselga J, Im YH, Im SA, Pivot X, Ross G, Clark E, Knott A, Swain SM. Health-related quality-of-life assessment in CLEOPATRA, a phase III study combining pertuzumab with trastuzumab and docetaxel in metastatic breast cancer. Ann Oncol. 2013 Oct;24(10):2630-2635. Epub 2013 Jul 17. [https://doi.org/10.1093/annonc/mdt274 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23868905/ PubMed] | ||
+ | ## '''Update:''' Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S, Clark E, Ross G, Benyunes MC, Cortés J; CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015 Feb 19;372(8):724-34. [https://doi.org/10.1056/NEJMoa1413513 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5584549/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25693012/ PubMed] | ||
+ | ## '''Update:''' Swain SM, Miles D, Kim SB, Im YH, Im SA, Semiglazov V, Ciruelos E, Schneeweiss A, Loi S, Monturus E, Clark E, Knott A, Restuccia E, Benyunes MC, Cortés J; CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020 Apr;21(4):519-530. Epub 2020 Mar 12. [https://doi.org/10.1016/s1470-2045(19)30863-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32171426/ PubMed] | ||
+ | # '''PUFFIN:''' Xu B, Li W, Zhang Q, Shao Z, Li Q, Wang X, Li H, Sun T, Yin Y, Zheng H, Feng J, Zhang H, Lei G, Restuccia E. Pertuzumab, trastuzumab, and docetaxel for Chinese patients with previously untreated HER2-positive locally recurrent or metastatic breast cancer (PUFFIN): a phase III, randomized, double-blind, placebo-controlled study. Breast Cancer Res Treat. 2020 Aug;182(3):689-697. Epub 2020 Jun 20. [https://doi.org/10.1007/s10549-020-05728-w link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7320929/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/32564260/ PubMed] [https://clinicaltrials.gov/study/NCT02896855 NCT02896855] | ||
+ | ##'''Update:''' Xu B, Li W, Zhang Q, Li Q, Wang X, Li H, Sun T, Yin Y, Zheng H, Feng J, Zhu H, Siddiqui A, Macharia H, Knott A. Pertuzumab, trastuzumab, and docetaxel for Chinese patients with previously untreated HER2-positive locally recurrent or metastatic breast cancer (PUFFIN): final analysis of a phase III, randomized, double-blind, placebo-controlled study. Breast Cancer Res Treat. 2023 Feb;197(3):503-513. Epub 2022 Dec 4. [https://doi.org/10.1007/s10549-022-06775-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9883304/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36463547/ PubMed] | ||
+ | # '''HERB TEA:''' UMIN000030783 | ||
+ | |||
+ | ==Trastuzumab monotherapy {{#subobject:9dedb2|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1 {{#subobject:9be86b|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1093/annonc/mdw622 Pagani et al. 2017 (SAKK 22/99)] | ||
+ | |1999-2013 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |Chemotherapy & Trastuzumab | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of TTP | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 4 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 2 mg/kg IV once on day 1 | ||
+ | '''7-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen variant #2, flat dose {{#subobject:1ac22c|Variant=1}}=== | ||
+ | {| class="wikitable" style="color:white; background-color:#f01e2c" | ||
+ | |<small><span style="color:white;">'''Historic variant'''</span></small> | ||
+ | |- | ||
+ | |} | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.1996.14.3.737 Baselga et al. 1996] | ||
+ | |Not reported | ||
+ | | style="background-color:#91cf61" |Phase 2 | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: this variant is of historical interest, only.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 250 mg IV once on day 1 | ||
+ | **Cycles 2 to 11: 100 mg IV once on day 1 | ||
+ | '''7-day cycle for 11 cycles''' | ||
+ | </div></div> | ||
+ | |||
+ | ===References=== | ||
+ | # Baselga J, Tripathy D, Mendelsohn J, Baughman S, Benz CC, Dantis L, Sklarin NT, Seidman AD, Hudis CA, Moore J, Rosen PP, Twaddell T, Henderson IC, Norton L. Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. J Clin Oncol. 1996 Mar;14(3):737-44. [https://doi.org/10.1200/JCO.1996.14.3.737 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8622019/ PubMed] | ||
+ | # '''SAKK 22/99:''' Pagani O, Klingbiel D, Ruhstaller T, Nolè F, Eppenberger S, Oehlschlegel C, Bernhard J, Brauchli P, Hess D, Mamot C, Munzone E, Pestalozzi B, Rabaglio M, Aebi S, Ribi K, Rochlitz C, Rothgiesser K, Thürlimann B, von Moos R, Zaman K, Goldhirsch A; Swiss Group for Clinical Cancer Research. Do all patients with advanced HER2 positive breast cancer need upfront-chemo when receiving trastuzumab? Randomized phase III trial SAKK 22/99. Ann Oncol. 2017 Feb 1;28(2):305-312. [https://doi.org/10.1093/annonc/mdw622 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27998961/ PubMed] [https://clinicaltrials.gov/study/NCT00004935 NCT00004935] | ||
+ | |||
+ | ==Trastuzumab emtansine monotherapy {{#subobject:d320be|Regimen=1}}== | ||
+ | T-DM1: '''<u>T</u>'''rastuzumab-'''<u>DM1</u>''' (Trastuzumab emtansine) | ||
+ | ===Example orders=== | ||
+ | *[[Example orders for trastuzumab emtansine (Kadcyla) in breast cancer]] | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:63b7de|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2012.44.9694 Hurvitz et al. 2013 (TDM4450g)] | ||
+ | |2008-2009 | ||
+ | |style="background-color:#1a9851"|Randomized Phase 2 (E-switch-ooc) | ||
+ | |[[#Docetaxel_.26_Trastuzumab_.28TH.29_3|TH]] | ||
+ | |style="background-color:#91cf60"|Seems to have superior PFS (co-primary endpoint)<br>Median PFS: 14.2 vs 9.2 mo<br>(HR 0.59, 95% CI 0.36-0.97) | ||
+ | |- | ||
+ | |rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455677/ Perez et al. 2016 (MARIANNE)] | ||
+ | |rowspan=2|2010-2012 | ||
+ | |rowspan=2 style="background-color:#1a9851"|Phase 3 (E-de-esc) | ||
+ | |1. [[#T-DM1_.26_Pertuzumab_999|T-DM1 & Pertuzumab]] | ||
+ | |style="background-color:#eeee01"|Non-inferior PFS (primary endpoint) | ||
+ | |- | ||
+ | |2a. [[#Docetaxel_.26_Trastuzumab_.28TH.29_3|TH (Docetaxel)]]<br>2b. [[#Paclitaxel_.26_Trastuzumab_.28TH.29_3|TH (Paclitaxel)]] | ||
+ | |style="background-color:#eeee01"|Non-inferior PFS (primary endpoint) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Antibody-drug conjugate therapy==== | ||
+ | *[[Trastuzumab emtansine (Kadcyla)]] 3.6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | <!-- Presented at the European Multidisciplinary Cancer Congress, Stockholm, Sweden, September 23-27, 2011, and the European Society of Medical Oncology Congress, Milan, Italy, October 8–12, 2010. --> | ||
+ | # '''TDM4450g:''' Hurvitz SA, Dirix L, Kocsis J, Bianchi GV, Lu J, Vinholes J, Guardino E, Song C, Tong B, Ng V, Chu YW, Perez EA. Phase II randomized study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2013 Mar 20;31(9):1157-63. Epub 2013 Feb 4. Erratum in: J Clin Oncol. 2013 Aug 10;31(23):2977. [https://doi.org/10.1200/jco.2012.44.9694 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23382472/ PubMed] [https://clinicaltrials.gov/study/NCT00679341 NCT00679341] | ||
+ | # '''MARIANNE:''' Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, Martin M, Pienkowski T, Pivot X, Burris H 3rd, Petersen JA, Stanzel S, Strasak A, Patre M, Ellis P. Trastuzumab emtansine with or without pertuzumab versus trastuzumab plus taxane for human epidermal growth factor receptor 2-positive, advanced breast cancer: primary results from the phase III MARIANNE study. J Clin Oncol. 2017 Jan 10;35(2):141-148. Epub 2016 Nov 7. [https://doi.org/10.1200/JCO.2016.67.4887 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455677/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28056202/ PubMed] [https://clinicaltrials.gov/study/NCT01120184 NCT01120184] | ||
+ | ## '''Update:''' Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, Martin M, Pienkowski T, Pivot XB, Burris HA 3rd, Petersen JA, De Haas S, Hoersch S, Patre M, Ellis PA. Trastuzumab emtansine with or without pertuzumab versus trastuzumab with taxane for human epidermal growth factor receptor 2-positive advanced breast cancer: final results from MARIANNE. Cancer. 2019 Nov 15;125(22):3974-3984. Epub 2019 Jul 18. [https://doi.org/10.1002/cncr.32392 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31318460/ PubMed] | ||
+ | ==Vinorelbine & Trastuzumab (VH) {{#subobject:59edc1|Regimen=1}}== | ||
+ | VH: '''<u>V</u>'''inorelbine & '''<u>H</u>'''erceptin (Trastuzumab) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, vinorelbine 25 mg/m<sup>2</sup>, weekly {{#subobject:947c3a|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1002/cncr.22885 Burstein et al. 2007 (TRAVIOTA)] | ||
+ | |2001-2003 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-switch-ic) | ||
+ | |1a. [[#Docetaxel_.26_Trastuzumab_.28TH.29_3|TH (Docetaxel)]]<br>1b. [[#Paclitaxel_.26_Trastuzumab_.28TH.29_3|TH (Paclitaxel)]] | ||
+ | |style="background-color:#d9ef8b"|Might have superior TTP (primary endpoint) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 4 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 2 mg/kg IV once on day 1 | ||
+ | '''7-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | |||
+ | ===Regimen variant #2, vinorelbine 30 mg/m<sup>2</sup>, 2 out of 3 weeks {{#subobject:fac964|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.2010.30.8213 Andersson et al. 2010 (HERNATA)] | ||
+ | |2004-2008 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-switch-ic) | ||
+ | |[[#Docetaxel_.26_Trastuzumab_.28TH.29_3|TH (Docetaxel)]] | ||
+ | |style="background-color:#ffffbf"|Did not meet primary endpoint of TTP | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV over 90 minutes once on day 1 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV over 30 minutes once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #3, vinorelbine 35 mg/m<sup>2</sup>, 2 out of 3 weeks {{#subobject:a6dae9|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.2010.30.8213 Andersson et al. 2010 (HERNATA)] | ||
+ | |2004-2008 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-switch-ic) | ||
+ | |[[#Docetaxel_.26_Trastuzumab_.28TH.29_3|TH (Docetaxel)]] | ||
+ | |style="background-color:#ffffbf"|Did not meet primary endpoint of TTP | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Vinorelbine (Navelbine)]] 35 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV over 90 minutes once on day 1 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV over 30 minutes once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''TRAVIOTA:''' Burstein HJ, Keshaviah A, Baron AD, Hart RD, Lambert-Falls R, Marcom PK, Gelman R, Winer EP. Trastuzumab plus vinorelbine or taxane chemotherapy for HER2-overexpressing metastatic breast cancer: the trastuzumab and vinorelbine or taxane study. Cancer. 2007 Sep 1;110(5):965-72. Epub 2007 Aug 20. [https://doi.org/10.1002/cncr.22885 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17614302/ PubMed] [https://clinicaltrials.gov/study/NCT00146549 NCT00146549] | ||
+ | # '''HERNATA:''' Andersson M, Lidbrink E, Bjerre K, Wist E, Enevoldsen K, Jensen AB, Karlsson P, Tange UB, Sørensen PG, Møller S, Bergh J, Langkjer ST. Phase III randomized study comparing docetaxel plus trastuzumab with vinorelbine plus trastuzumab as first-line therapy of metastatic or locally advanced human epidermal growth factor receptor 2-positive breast cancer: the HERNATA study. J Clin Oncol. 2011 Jan 20;29(3):264-71. Epub 2010 Dec 13. [https://doi.org/10.1200/JCO.2010.30.8213 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21149659/ PubMed] [https://clinicaltrials.gov/study/NCT00430001 NCT00430001] | ||
+ | |||
+ | =Metastatic or unresectable disease, subsequent lines= | ||
+ | ==Capecitabine & Lapatinib {{#subobject:5474dd|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:6d0733|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/NEJMoa064320 Geyer et al. 2006 (EGF100151)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-10-1 <span style="color:white;">ESMO-MCBS (3)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2004-03-29 to 2005-11-15 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-RT-esc) | ||
+ | |[[Breast_cancer,_HER2-positive_-_historical#Capecitabine_monotherapy|Capecitabine]] | ||
+ | |style="background-color:#1a9850"|Superior TTP<sup>1</sup> (primary endpoint)<br>(HR 0.57, 95% CI 0.43-0.77)<br><br>Did not meet secondary endpoint of OS<br>Median OS: 75 vs 64.7 weeks<br>(HR 0.87, 95% CI 0.71-1.08) | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125250/ Verma et al. 2012 (EMILIA)] | ||
+ | |2009-2011 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#Trastuzumab_emtansine_monotherapy_4|T-DM1]] | ||
+ | |style="background-color:#d73027"|Inferior OS | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.2014.57.1794 Pivot et al. 2015 (CEREBEL)] | ||
+ | |2009-2012 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-switch-ic) | ||
+ | |[[#Capecitabine_.26_Trastuzumab_.28XH.29_2|Capecitabine & Trastuzumab]] | ||
+ | |style="background-color:#ffffbf"|Did not meet primary endpoint of CNS metastases as first site of relapse | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7499616/ Saura et al. 2020 (NALA)] | ||
+ | |2013-2017 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#Capecitabine_.26_Neratinib|Capecitabine & Neratinib]] | ||
+ | |style="background-color:#d73027"|Inferior PFS | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/s1470-2045(20)30702-6 Xu et al. 2021 (PHOEBE)] | ||
+ | |2017-07-31 to 2018-10-30 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#Capecitabine_.26_Pyrotinib|Capecitabine & Pyrotinib]] | ||
+ | |style="background-color:#d73027"|Inferior PFS | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/s0140-6736(23)00725-0 André et al. 2023 (DESTINY-Breast02)] | ||
+ | |2018-09-06 to 2020-12-31 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Trastuzumab_deruxtecan_monotherapy|T-DXd]] | ||
+ | |style="background-color:#d73027"|Inferior PFS | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Reported efficacy for PFS for EGF100151 is based on the 2008 update.''<br> | ||
+ | ''<sup>2</sup>Reported efficacy for OS for EGF100151 is based on the 2010 update.''<br> | ||
+ | ''Note: the primary endpoint of CEREBEL was incidence of CNS as site of first relapse; this was very low in both arms, with no statistically significant difference.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *EGF100151: an anthracycline, a taxane, and trastuzumab | ||
+ | *EMILIA, PHOEBE, DESTINY-Breast02: trastuzumab and a taxane | ||
+ | *CEREBEL: prior anthracycline and/or taxanes | ||
+ | *NALA: 2 or more previous HER2-directed therapies in the metastatic setting | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Lapatinib (Tykerb)]] 1250 mg PO once per day on days 1 to 21 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | |||
+ | ===References=== | ||
+ | # '''EGF100151:''' Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006 Dec 28;355(26):2733-43. [https://doi.org/10.1056/NEJMoa064320 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17192538/ PubMed] [https://clinicaltrials.gov/study/NCT00078572 NCT00078572] | ||
+ | ## '''Update:''' Cameron D, Casey M, Press M, Lindquist D, Pienkowski T, Romieu CG, Chan S, Jagiello-Gruszfeld A, Kaufman B, Crown J, Chan A, Campone M, Viens P, Davidson N, Gorbounova V, Raats JI, Skarlos D, Newstat B, Roychowdhury D, Paoletti P, Oliva C, Rubin S, Stein S, Geyer CE. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat. 2008 Dec;112(3):533-43. Epub 2008 Jan 11. [https://doi.org/10.1007/s10549-007-9885-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18188694/ PubMed] | ||
+ | ## '''Update:''' Cameron D, Casey M, Oliva C, Newstat B, Imwalle B, Geyer CE. Lapatinib plus capecitabine in women with HER-2-positive advanced breast cancer: final survival analysis of a phase III randomized trial. Oncologist. 2010;15(9):924-34. Epub 2010 Aug 24. [https://doi.org/10.1634/theoncologist.2009-0181 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3228041/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20736298/ PubMed] | ||
+ | # '''EMILIA:''' Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh DY, Diéras V, Guardino E, Fang L, Lu MW, Olsen S, Blackwell K; EMILIA Study Group. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012 Nov 8;367(19):1783-91. Epub 2012 Oct 1. Erratum in: N Engl J Med. 2013 Jun 20;368(25):2442. [https://doi.org/10.1056/NEJMoa1209124 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125250/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23020162/ PubMed] [https://clinicaltrials.gov/study/NCT00829166 NCT00829166] | ||
+ | ## '''PRO analysis:''' Welslau M, Diéras V, Sohn JH, Hurvitz SA, Lalla D, Fang L, Althaus B, Guardino E, Miles D. Patient-reported outcomes from EMILIA, a randomized phase 3 study of trastuzumab emtansine (T-DM1) versus capecitabine and lapatinib in human epidermal growth factor receptor 2-positive locally advanced or metastatic breast cancer. Cancer. 2014 Mar 1;120(5):642-51. Epub 2013 Nov 12. [https://doi.org/10.1002/cncr.28465 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24222194/ PubMed] | ||
+ | ## '''Update:''' Diéras V, Miles D, Verma S, Pegram M, Welslau M, Baselga J, Krop IE, Blackwell K, Hoersch S, Xu J, Green M, Gianni L. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2017 Jun;18(6):732-742. Epub 2017 May 16. [https://doi.org/10.1016/S1470-2045(17)30312-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5531181/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28526536/ PubMed] | ||
+ | # '''CEREBEL:''' Pivot X, Manikhas A, Żurawski B, Chmielowska E, Karaszewska B, Allerton R, Chan S, Fabi A, Bidoli P, Gori S, Ciruelos E, Dank M, Hornyak L, Margolin S, Nusch A, Parikh R, Nagi F, DeSilvio M, Santillana S, Swaby RF, Semiglazov V. CEREBEL (EGF111438): A phase III, randomized, open-label study of lapatinib plus capecitabine versus trastuzumab plus capecitabine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2015 May 10;33(14):1564-73. Epub 2015 Jan 20. [https://doi.org/10.1200/JCO.2014.57.1794 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25605838/ PubMed] [https://clinicaltrials.gov/study/NCT00820222 NCT00820222] | ||
+ | <!-- # '''Abstract:''' Cristina Saura, Mafalda Oliveira, Yin-Hsun Feng, Ming-Shen Dai, Sara A. Hurvitz, Sung-Bae Kim, Beverly Moy, Suzette Delaloge, William John Gradishar, Norikazu Masuda, Marketa Palacova, Maureen E. Trudeau, Johanna Mattson, Yoon Sim Yap, Richard Bryce, Bin Yao, Judith D. Bebchuk, Kiana Keyvanjah, Adam Brufsky, and NALA Investigators. Neratinib + capecitabine versus lapatinib + capecitabine in patients with HER2+ metastatic breast cancer previously treated with ≥ 2 HER2-directed regimens: Findings from the multinational, randomized, phase III NALA trial. Journal of Clinical Oncology 2019 37:15_suppl, 1002-1002 [https://doi.org/10.1200/JCO.2019.37.15_suppl.1002 link to abstract] --> | ||
+ | #'''NALA:''' Saura C, Oliveira M, Feng YH, Dai MS, Chen SW, Hurvitz SA, Kim SB, Moy B, Delaloge S, Gradishar W, Masuda N, Palacova M, Trudeau ME, Mattson J, Yap YS, Hou MF, De Laurentiis M, Yeh YM, Chang HT, Yau T, Wildiers H, Haley B, Fagnani D, Lu YS, Crown J, Lin J, Takahashi M, Takano T, Yamaguchi M, Fujii T, Yao B, Bebchuk J, Keyvanjah K, Bryce R, Brufsky A; NALA Investigators. Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial. J Clin Oncol. 2020 Sep 20;38(27):3138-3149. Epub 2020 Jul 17. [https://doi.org/10.1200/jco.20.00147 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7499616/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32678716/ PubMed] [https://clinicaltrials.gov/study/NCT01808573 NCT01808573] | ||
+ | #'''PHOEBE:''' Xu B, Yan M, Ma F, Hu X, Feng J, Ouyang Q, Tong Z, Li H, Zhang Q, Sun T, Wang X, Yin Y, Cheng Y, Li W, Gu Y, Chen Q, Liu J, Cheng J, Geng C, Qin S, Wang S, Lu J, Shen K, Liu Q, Wang X, Wang H, Luo T, Yang J, Wu Y, Yu Z, Zhu X, Chen C, Zou J; PHOEBE Investigators. Pyrotinib plus capecitabine versus lapatinib plus capecitabine for the treatment of HER2-positive metastatic breast cancer (PHOEBE): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2021 Mar;22(3):351-360. Epub 2021 Feb 11. [https://doi.org/10.1016/s1470-2045(20)30702-6 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33581774/ PubMed] [https://clinicaltrials.gov/study/NCT03080805 NCT03080805] | ||
+ | #'''DESTINY-Breast02:''' André F, Hee Park Y, Kim SB, Takano T, Im SA, Borges G, Lima JP, Aksoy S, Gavila Gregori J, De Laurentiis M, Bianchini G, Roylance R, Miyoshi Y, Armstrong A, Sinha R, Ruiz Borrego M, Lim E, Ettl J, Yerushalmi R, Zagouri F, Duhoux FP, Fehm T, Gambhire D, Cathcart J, Wu C, Chu C, Egorov A, Krop I. Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2023 May 27;401(10390):1773-1785. Epub 2023 Apr 20. [https://doi.org/10.1016/s0140-6736(23)00725-0 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/37086745/ PubMed] [https://clinicaltrials.gov/study/NCT03523585 NCT03523585] | ||
+ | ##'''PRO analysis:''' Fehm T, Cottone F, Dunton K, André F, Krop I, Park YH, De Laurentiis M, Miyoshi Y, Armstrong A, Borrego MR, Yerushalmi R, Duhoux FP, Takano T, Lu W, Egorov A, Kim SB. Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): patient-reported outcomes from a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2024 May;25(5):614-625. [https://doi.org/10.1016/s1470-2045(24)00128-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38697155/ PubMed] | ||
+ | |||
+ | ==Capecitabine & Margetuximab {{#subobject:7mz1hq|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:1de6ad|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7823434/ Rugo et al. 2021 (SOPHIA)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-242-1 <span style="color:white;">ESMO-MCBS (2)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2015-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic) | ||
+ | |1a. [[#Eribulin_.26_Trastuzumab|Eribulin & Trastuzumab]]<br>1b. [[#Gemcitabine_.26_Trastuzumab|Gemcitabine & Trastuzumab]]<br>1c. [[#Vinorelbine_.26_Trastuzumab_.28VH.29|VH]]<br>1d. [[#Capecitabine_.26_Trastuzumab_.28XH.29_2|XH]] | ||
+ | | style="background-color:#91cf60" |Seems to have superior PFS (primary endpoint)<br>Median PFS: 6 vs 5 mo<br>(HR 0.76, 95% CI 0.59-0.98)<br><br>Did not meet secondary endpoint of OS<sup>1</sup><br>Median OS: 21.6 vs 21.9 mo<br>(HR 0.95, 95% CI 0.77-1.17) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the 2022 update.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Margetuximab (Margenza)]] 15 mg/kg IV over 120 minutes once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''SOPHIA:''' Rugo HS, Im SA, Cardoso F, Cortés J, Curigliano G, Musolino A, Pegram MD, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Kaufman B, Yerushalmi R, Fasching PA, Nordstrom JL, Bonvini E, Koenig S, Edlich S, Hong S, Rock EP, Gradishar WJ; SOPHIA Study Group. Efficacy of Margetuximab vs Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Apr 1;7(4):573-584. [https://doi.org/10.1001/jamaoncol.2020.7932 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7823434/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33480963/ PubMed] [https://clinicaltrials.gov/study/NCT02492711 NCT02492711] | ||
+ | ##'''Update:''' Rugo HS, Im SA, Cardoso F, Cortes J, Curigliano G, Musolino A, Pegram MD, Bachelot T, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Schwartz GN, Pluard TJ, Ricci F, Gwin WR 3rd, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Gal-Yam EN, Yerushalmi R, Fasching PA, Kaufman PA, Ashley EJ, Perez-Olle R, Hong S, Rosales MK, Gradishar WJ; SOPHIA Study Group. Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial. J Clin Oncol. 2023 Jan 10;41(2):198-205. Epub 2022 Nov 4. [https://doi.org/10.1200/jco.21.02937 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839304/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36332179/ PubMed] | ||
+ | ==Capecitabine & Neratinib {{#subobject:01baec|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:3a0475|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.2014.56.3809 Saura et al. 2014 (3144A1-2206)] | ||
+ | |2008 to not reported | ||
+ | |style="background-color:#91cf61"|Phase 1/2 | ||
+ | |style="background-color:#d3d3d3"| | ||
+ | | style="background-color:#bfd3e6" |ORR: 64% | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7499616/ Saura et al. 2020 (NALA)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-225-1 <span style="color:white;">ESMO-MCBS (1)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2013-2017 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic) | ||
+ | |[[#Capecitabine_.26_Lapatinib_2|Capecitabine & Lapatinib]] | ||
+ | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 8.8 vs 6.6 mo<br>(HR 0.76, 95% CI 0.63-0.93) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Capecitabine (Xeloda)]] 750 mg/m<sup>2</sup> PO twice per day on days 1 to 14 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Neratinib (Nerlynx)]] 240 mg PO once per day on days 1 to 21 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''3144A1-2206:''' Saura C, Garcia-Saenz JA, Xu B, Harb W, Moroose R, Pluard T, Cortés J, Kiger C, Germa C, Wang K, Martin M, Baselga J, Kim SB. Safety and efficacy of neratinib in combination with capecitabine in patients with metastatic human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2014 Nov 10;32(32):3626-33. Epub 2014 Oct 6. [https://doi.org/10.1200/JCO.2014.56.3809 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25287822/ PubMed] [https://clinicaltrials.gov/study/NCT00741260 NCT00741260] | ||
+ | <!-- # '''Abstract:''' Cristina Saura, Mafalda Oliveira, Yin-Hsun Feng, Ming-Shen Dai, Sara A. Hurvitz, Sung-Bae Kim, Beverly Moy, Suzette Delaloge, William John Gradishar, Norikazu Masuda, Marketa Palacova, Maureen E. Trudeau, Johanna Mattson, Yoon Sim Yap, Richard Bryce, Bin Yao, Judith D. Bebchuk, Kiana Keyvanjah, Adam Brufsky, and NALA Investigators. Neratinib + capecitabine versus lapatinib + capecitabine in patients with HER2+ metastatic breast cancer previously treated with ≥ 2 HER2-directed regimens: Findings from the multinational, randomized, phase III NALA trial. Journal of Clinical Oncology 2019 37:15_suppl, 1002-1002 [https://doi.org/10.1200/JCO.2019.37.15_suppl.1002 link to abstract] --> | ||
+ | #'''NALA:''' Saura C, Oliveira M, Feng YH, Dai MS, Chen SW, Hurvitz SA, Kim SB, Moy B, Delaloge S, Gradishar W, Masuda N, Palacova M, Trudeau ME, Mattson J, Yap YS, Hou MF, De Laurentiis M, Yeh YM, Chang HT, Yau T, Wildiers H, Haley B, Fagnani D, Lu YS, Crown J, Lin J, Takahashi M, Takano T, Yamaguchi M, Fujii T, Yao B, Bebchuk J, Keyvanjah K, Bryce R, Brufsky A; NALA Investigators. Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial. J Clin Oncol. 2020 Sep 20;38(27):3138-3149. Epub 2020 Jul 17. [https://doi.org/10.1200/jco.20.00147 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7499616/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32678716/ PubMed] [https://clinicaltrials.gov/study/NCT01808573 NCT01808573] | ||
+ | |||
+ | ==Capecitabine & Pyrotinib {{#subobject:5ug92dd|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:9ugr33|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/s1470-2045(20)30702-6 Xu et al. 2021 (PHOEBE)] | ||
+ | |2017-07-31 to 2018-10-30 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-switch-ic) | ||
+ | |[[#Capecitabine_.26_Lapatinib_2|Capecitabine & Lapatinib]] | ||
+ | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 12.5 vs 6.8 mo<br>(HR 0.39, 95% CI 0.27-0.56) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Pyrotinib (Irene)]] 400 mg PO once per day on days 1 to 21 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''PHOEBE:''' Xu B, Yan M, Ma F, Hu X, Feng J, Ouyang Q, Tong Z, Li H, Zhang Q, Sun T, Wang X, Yin Y, Cheng Y, Li W, Gu Y, Chen Q, Liu J, Cheng J, Geng C, Qin S, Wang S, Lu J, Shen K, Liu Q, Wang X, Wang H, Luo T, Yang J, Wu Y, Yu Z, Zhu X, Chen C, Zou J; PHOEBE Investigators. Pyrotinib plus capecitabine versus lapatinib plus capecitabine for the treatment of HER2-positive metastatic breast cancer (PHOEBE): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2021 Mar;22(3):351-360. Epub 2021 Feb 11. [https://doi.org/10.1016/s1470-2045(20)30702-6 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33581774/ PubMed] [https://clinicaltrials.gov/study/NCT03080805 NCT03080805] | ||
+ | |||
+ | ==Capecitabine & Trastuzumab (XH) {{#subobject:8d0dd5|Regimen=1}}== | ||
+ | XH: '''<u>X</u>'''eloda (Capecitabine) & '''<u>H</u>'''erceptin (Trastuzumab) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, 2000/6, with loading dose {{#subobject:776bcc|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7823434/ Rugo et al. 2021 (SOPHIA)] | ||
+ | |2015-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#Capecitabine_.26_Margetuximab|Capecitabine & Margetuximab]]<br>1b. [[#Eribulin_.26_Margetuximab|Eribulin & Margetuximab]]<br>1c. [[#Gemcitabine_.26_Margetuximab|Gemcitabine & Margetuximab]]<br>1d. [[#Vinorelbine_.26_Margetuximab|Vinorelbine & Margetuximab]] | ||
+ | | style="background-color:#fc8d59" |Seems to have inferior PFS | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/nejmoa1914609 Murthy et al. 2019 (HER2CLIMB)] | ||
+ | |2016-2019 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#Capecitabine_.26_Trastuzumab_.28XH.29_.26_Tucatinib|XH & Tucatinib]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, 2500/6, with loading dose {{#subobject:663bcc|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2007.11.9776 Bartsch et al. 2007] | ||
+ | |2004-2006 | ||
+ | |style="background-color:#91cf61"|Phase 2 | ||
+ | |style="background-color:#d3d3d3"| | ||
+ | |style="background-color:#d3d3d3"| | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.2014.57.1794 Pivot et al. 2015 (CEREBEL)] | ||
+ | |2009-2012 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#Capecitabine_.26_Lapatinib_2|Capecitabine & Lapatanib]] | ||
+ | |style="background-color:#ffffbf"|Did not meet primary endpoint of CNS metastases as first site of relapse | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.2016.70.6267 Urruticoechea et al. 2017 (PHEREXA)] | ||
+ | |2010-2013 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#XHP|XHP]] | ||
+ | |style="background-color:#fee08b"|Might have inferior PFS | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ Yamamoto et al. 2022 (PRECIOUS)] | ||
+ | |2015-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#THP_.28Docetaxel.29_3|THP (Docetaxel)]]<br>1b. [[#THP_.28Paclitaxel.29|THP (Paclitaxel)]]<br>1c. [[#nab-Paclitaxel.2C_Pertuzumab.2C_Trastuzumab|nab-Paclitaxel, Pertuzumab, Trastuzumab]]<br>1d. [[#VHP|VHP]]<br>1e. [[#EHP|EHP]]<br>1f. [[#XHP|XHP]]<br>1g. [[#GHP|GHP]] | ||
+ | | style="background-color:#fee08b" |Might have inferior OS | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/s0140-6736(23)00725-0 André et al. 2023 (DESTINY-Breast02)] | ||
+ | |2018-09-06 to 2020-12-31 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Trastuzumab_deruxtecan_monotherapy|T-DXd]] | ||
+ | |style="background-color:#d73027"|Inferior PFS | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: the only difference between this and the next variant is the use of a loading dose of trastuzumab. The primary endpoint of CEREBEL was incidence of CNS as site of first relapse; this was very low in both arms, with no statistically significant difference.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *Bartsch et al. 2007: anthracycline and docetaxel or vinorelbine failure and prior trastuzumab exposure | ||
+ | *CEREBEL: prior anthracycline and/or taxanes | ||
+ | *PHEREXA: taxane | ||
+ | *PRECIOUS: History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this. | ||
+ | *DESTINY-Breast02: trastuzumab and a taxane | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO twice per day on days 1 to 14 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #3, 2500/6, no loading dose {{#subobject:e38ff|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2008.19.6618 von Minckwitz et al. 2009 (GBG 26/BIG 3-05)] | ||
+ | |2003 to not reported | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |[[Breast_cancer,_HER2-positive_-_historical#Capecitabine_monotherapy_3|Capecitabine]] | ||
+ | |style="background-color:#91cf60"|Seems to have superior TTP (primary endpoint)<br>Median TTP: 8.2 vs 5.6 mo<br>(HR 0.69, 95% CI 0.48-0.97) | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: This was a continuation of trastuzumab so there is no loading dose.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO twice per day on days 1 to 14 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # Bartsch R, Wenzel C, Altorjai G, Pluschnig U, Rudas M, Mader RM, Gnant M, Zielinski CC, Steger GG. Capecitabine and trastuzumab in heavily pretreated metastatic breast cancer. J Clin Oncol. 2007 Sep 1;25(25):3853-8. Epub 2007 Aug 6. [https://doi.org/10.1200/jco.2007.11.9776 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17679724/ PubMed] | ||
+ | # '''GBG 26/BIG 3-05:''' von Minckwitz G, du Bois A, Schmidt M, Maass N, Cufer T, de Jongh FE, Maartense E, Zielinski C, Kaufmann M, Bauer W, Baumann KH, Clemens MR, Duerr R, Uleer C, Andersson M, Stein RC, Nekljudova V, Loibl S. Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: a German Breast Group 26/Breast International Group 03-05 study. J Clin Oncol. 2009 Apr 20;27(12):1999-2006. Epub 2009 Mar 16. [https://doi.org/10.1200/jco.2008.19.6618 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19289619/ PubMed] [https://clinicaltrials.gov/study/NCT00148876 NCT00148876] | ||
+ | ## '''Update:''' von Minckwitz G, Schwedler K, Schmidt M, Barinoff J, Mundhenke C, Cufer T, Maartense E, de Jongh FE, Baumann KH, Bischoff J, Harbeck N, Lück HJ, Maass N, Zielinski C, Andersson M, Stein RC, Nekljudova V, Loibl S; GBG 26/BIG 03-05 study group and participating investigators. Trastuzumab beyond progression: overall survival analysis of the GBG 26/BIG 3-05 phase III study in HER2-positive breast cancer. Eur J Cancer. 2011 Oct;47(15):2273-81. Epub 2011 Jul 7. [https://doi.org/10.1016/j.ejca.2011.06.021 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21741829/ PubMed] | ||
+ | # '''CEREBEL:''' Pivot X, Manikhas A, Żurawski B, Chmielowska E, Karaszewska B, Allerton R, Chan S, Fabi A, Bidoli P, Gori S, Ciruelos E, Dank M, Hornyak L, Margolin S, Nusch A, Parikh R, Nagi F, DeSilvio M, Santillana S, Swaby RF, Semiglazov V. CEREBEL (EGF111438): A phase III, randomized, open-label study of lapatinib plus capecitabine versus trastuzumab plus capecitabine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2015 May 10;33(14):1564-73. Epub 2015 Jan 20. [https://doi.org/10.1200/JCO.2014.57.1794 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25605838/ PubMed] [https://clinicaltrials.gov/study/NCT00820222 NCT00820222] | ||
+ | # '''PHEREXA:''' Urruticoechea A, Rizwanullah M, Im SA, Ruiz ACS, Láng I, Tomasello G, Douthwaite H, Badovinac Crnjevic T, Heeson S, Eng-Wong J, Muñoz M. Randomized phase III trial of trastuzumab plus capecitabine with or without pertuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who experienced disease progression during or after trastuzumab-based therapy. J Clin Oncol. 2017 Sep 10;35(26):3030-3038. Epub 2017 Apr 24. [https://doi.org/10.1200/JCO.2016.70.6267 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28437161/ PubMed] [https://clinicaltrials.gov/study/NCT01026142 NCT01026142] | ||
+ | # '''HER2CLIMB:''' Murthy RK, Loi S, Okines A, Paplomata E, Hamilton E, Hurvitz SA, Lin NU, Borges V, Abramson V, Anders C, Bedard PL, Oliveira M, Jakobsen E, Bachelot T, Shachar SS, Müller V, Braga S, Duhoux FP, Greil R, Cameron D, Carey LA, Curigliano G, Gelmon K, Hortobagyi G, Krop I, Loibl S, Pegram M, Slamon D, Palanca-Wessels MC, Walker L, Feng W, Winer EP. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. N Engl J Med. 2020 Feb 13;382(7):597-609. Epub 2019 Dec 11. Erratum in: N Engl J Med. 2020 Feb 6;382(6):586. [https://doi.org/10.1056/nejmoa1914609 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31825569/ PubMed] [https://clinicaltrials.gov/study/NCT02614794 NCT02614794] | ||
+ | ## '''Subgroup analysis:''' Lin NU, Borges V, Anders C, Murthy RK, Paplomata E, Hamilton E, Hurvitz S, Loi S, Okines A, Abramson V, Bedard PL, Oliveira M, Mueller V, Zelnak A, DiGiovanna MP, Bachelot T, Chien AJ, O'Regan R, Wardley A, Conlin A, Cameron D, Carey L, Curigliano G, Gelmon K, Loibl S, Mayor J, McGoldrick S, An X, Winer EP. Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial. J Clin Oncol. 2020 Aug 10;38(23):2610-2619. Epub 2020 May 29. [https://doi.org/10.1200/jco.20.00775 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403000/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32468955/ PubMed] | ||
+ | ##'''Update:''' Curigliano G, Mueller V, Borges V, Hamilton E, Hurvitz S, Loi S, Murthy R, Okines A, Paplomata E, Cameron D, Carey LA, Gelmon K, Hortobagyi GN, Krop I, Loibl S, Pegram M, Slamon D, Ramos J, Feng W, Winer E. Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysis. Ann Oncol. 2022 Mar;33(3):321-329. Epub 2021 Dec 23. [https://doi.org/10.1016/j.annonc.2021.12.005 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34954044/ PubMed] | ||
+ | # '''SOPHIA:''' Rugo HS, Im SA, Cardoso F, Cortés J, Curigliano G, Musolino A, Pegram MD, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Kaufman B, Yerushalmi R, Fasching PA, Nordstrom JL, Bonvini E, Koenig S, Edlich S, Hong S, Rock EP, Gradishar WJ; SOPHIA Study Group. Efficacy of Margetuximab vs Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Apr 1;7(4):573-584. [https://doi.org/10.1001/jamaoncol.2020.7932 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7823434/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33480963/ PubMed] [https://clinicaltrials.gov/study/NCT02492711 NCT02492711] | ||
+ | ##'''Update:''' Rugo HS, Im SA, Cardoso F, Cortes J, Curigliano G, Musolino A, Pegram MD, Bachelot T, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Schwartz GN, Pluard TJ, Ricci F, Gwin WR 3rd, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Gal-Yam EN, Yerushalmi R, Fasching PA, Kaufman PA, Ashley EJ, Perez-Olle R, Hong S, Rosales MK, Gradishar WJ; SOPHIA Study Group. Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial. J Clin Oncol. 2023 Jan 10;41(2):198-205. Epub 2022 Nov 4. [https://doi.org/10.1200/jco.21.02937 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839304/ linnk to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36332179/ PubMed] | ||
+ | #'''PRECIOUS:''' Yamamoto Y, Iwata H, Taira N, Masuda N, Takahashi M, Yoshinami T, Ueno T, Toyama T, Yamanaka T, Takano T, Kashiwaba M, Tsugawa K, Hasegawa Y, Tamura K, Tada H, Hara F, Fujisawa T, Niikura N, Saji S, Morita S, Toi M, Ohno S. Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS). Cancer Sci. 2022 Sep;113(9):3169-3179. Epub 2022 Jul 23. [https://doi.org/10.1111/cas.15474 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ link to PMC article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/35754298/ PubMed] UMIN000018202 | ||
+ | #'''DESTINY-Breast02:''' André F, Hee Park Y, Kim SB, Takano T, Im SA, Borges G, Lima JP, Aksoy S, Gavila Gregori J, De Laurentiis M, Bianchini G, Roylance R, Miyoshi Y, Armstrong A, Sinha R, Ruiz Borrego M, Lim E, Ettl J, Yerushalmi R, Zagouri F, Duhoux FP, Fehm T, Gambhire D, Cathcart J, Wu C, Chu C, Egorov A, Krop I. Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2023 May 27;401(10390):1773-1785. Epub 2023 Apr 20. [https://doi.org/10.1016/s0140-6736(23)00725-0 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/37086745/ PubMed] [https://clinicaltrials.gov/study/NCT03523585 NCT03523585] | ||
+ | ##'''PRO analysis:''' Fehm T, Cottone F, Dunton K, André F, Krop I, Park YH, De Laurentiis M, Miyoshi Y, Armstrong A, Borrego MR, Yerushalmi R, Duhoux FP, Takano T, Lu W, Egorov A, Kim SB. Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): patient-reported outcomes from a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2024 May;25(5):614-625. [https://doi.org/10.1016/s1470-2045(24)00128-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38697155/ PubMed] | ||
+ | |||
+ | ==Capecitabine & Trastuzumab (XH) & Tucatinib {{#subobject:8d0gg5|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:771gcc|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/nejmoa1914609 Murthy et al. 2019 (HER2CLIMB)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-167-1 <span style="color:white;">ESMO-MCBS (4)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2016-2019 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-RT-esc) | ||
+ | |[[#Capecitabine_.26_Trastuzumab_.28XH.29_2|XH]] | ||
+ | | style="background-color:#1a9850" |Superior PFS<sup>1</sup> (primary endpoint)<br>Median PFS: 7.6 vs 4.9 mo<br>(HR 0.57, 95% CI 0.47-0.70)<br><br>Superior OS<sup>1</sup> (secondary endpoint)<br>Median OS: 24.7 vs 19.2 mo<br>(HR 0.73, 95% CI 0.59-0.90) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the 2021 update.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Tucatinib (Tukysa)]] 300 mg PO twice per day on days 1 to 21 | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''HER2CLIMB:''' Murthy RK, Loi S, Okines A, Paplomata E, Hamilton E, Hurvitz SA, Lin NU, Borges V, Abramson V, Anders C, Bedard PL, Oliveira M, Jakobsen E, Bachelot T, Shachar SS, Müller V, Braga S, Duhoux FP, Greil R, Cameron D, Carey LA, Curigliano G, Gelmon K, Hortobagyi G, Krop I, Loibl S, Pegram M, Slamon D, Palanca-Wessels MC, Walker L, Feng W, Winer EP. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. N Engl J Med. 2020 Feb 13;382(7):597-609. Epub 2019 Dec 11. Erratum in: N Engl J Med. 2020 Feb 6;382(6):586. [https://doi.org/10.1056/nejmoa1914609 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31825569/ PubMed] [https://clinicaltrials.gov/study/NCT02614794 NCT02614794] | ||
+ | ## '''Subgroup analysis:''' Lin NU, Borges V, Anders C, Murthy RK, Paplomata E, Hamilton E, Hurvitz S, Loi S, Okines A, Abramson V, Bedard PL, Oliveira M, Mueller V, Zelnak A, DiGiovanna MP, Bachelot T, Chien AJ, O'Regan R, Wardley A, Conlin A, Cameron D, Carey L, Curigliano G, Gelmon K, Loibl S, Mayor J, McGoldrick S, An X, Winer EP. Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial. J Clin Oncol. 2020 Aug 10;38(23):2610-2619. Epub 2020 May 29. [https://doi.org/10.1200/jco.20.00775 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403000/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32468955/ PubMed] | ||
+ | ##'''Update:''' Curigliano G, Mueller V, Borges V, Hamilton E, Hurvitz S, Loi S, Murthy R, Okines A, Paplomata E, Cameron D, Carey LA, Gelmon K, Hortobagyi GN, Krop I, Loibl S, Pegram M, Slamon D, Ramos J, Feng W, Winer E. Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysis. Ann Oncol. 2022 Mar;33(3):321-329. Epub 2021 Dec 23. [https://doi.org/10.1016/j.annonc.2021.12.005 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34954044/ PubMed] | ||
+ | |||
+ | ==Docetaxel & Trastuzumab (TH) {{#subobject:h17645|Regimen=1}}== | ||
+ | TH: '''<u>T</u>'''axotere (Docetaxel) & '''<u>H</u>'''erceptin (Trastuzumab) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, 60 mg/m<sup>2</sup> docetaxel {{#subobject:d6djtv|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ Yamamoto et al. 2022 (PRECIOUS)] | ||
+ | |2015-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#THP_.28Docetaxel.29_3|THP (Docetaxel)]]<br>1b. [[#THP_.28Paclitaxel.29|THP (Paclitaxel)]]<br>1c. [[#nab-Paclitaxel.2C_Pertuzumab.2C_Trastuzumab|nab-Paclitaxel, Pertuzumab, Trastuzumab]]<br>1d. [[#VHP|VHP]]<br>1e. [[#EHP|EHP]]<br>1f. [[#XHP|XHP]]<br>1g. [[#GHP|GHP]] | ||
+ | | style="background-color:#fee08b" |Might have inferior OS | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this. | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, 75 mg/m<sup>2</sup> docetaxel {{#subobject:d6jg9v|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ Yamamoto et al. 2022 (PRECIOUS)] | ||
+ | |2015-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#THP_.28Docetaxel.29_3|THP (Docetaxel)]]<br>1b. [[#THP_.28Paclitaxel.29|THP (Paclitaxel)]]<br>1c. [[#nab-Paclitaxel.2C_Pertuzumab.2C_Trastuzumab|nab-Paclitaxel, Pertuzumab, Trastuzumab]]<br>1d. [[#VHP|VHP]]<br>1e. [[#EHP|EHP]]<br>1f. [[#XHP|XHP]]<br>1g. [[#GHP|GHP]] | ||
+ | | style="background-color:#fee08b" |Might have inferior OS | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this. | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''PRECIOUS:''' Yamamoto Y, Iwata H, Taira N, Masuda N, Takahashi M, Yoshinami T, Ueno T, Toyama T, Yamanaka T, Takano T, Kashiwaba M, Tsugawa K, Hasegawa Y, Tamura K, Tada H, Hara F, Fujisawa T, Niikura N, Saji S, Morita S, Toi M, Ohno S. Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS). Cancer Sci. 2022 Sep;113(9):3169-3179. Epub 2022 Jul 23. [https://doi.org/10.1111/cas.15474 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ link to PMC article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/35754298/ PubMed] UMIN000018202 | ||
+ | ==EHP {{#subobject:u818jj|Regimen=1}}== | ||
+ | EHP: '''<u>E</u>'''ribulin, '''<u>H</u>'''erceptin (Trastuzumab), '''<u>P</u>'''ertuzumab | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:1ui521|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ Yamamoto et al. 2022 (PRECIOUS)] | ||
+ | |2015-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |1a. [[#Docetaxel_.26_Trastuzumab_.28TH.29_4|TH (Docetaxel)]]<br>1b. [[#Paclitaxel_.26_Trastuzumab_.28TH.29_4|TH (Paclitaxel)]]<br>1c. [[#nab-Paclitaxel_.26_Trastuzumab_2|nab-Paclitaxel & Trastuzumab]]<br>1d. [[#Vinorelbine_.26_Trastuzumab_.28VH.29_2|VH]]<br>1e. [[#Eribulin_.26_Trastuzumab|EH]]<br>1f. [[#Capecitabine_.26_Trastuzumab_.28XH.29_2|XH]]<br>1g. [[#Gemcitabine_.26_Trastuzumab|GH]] | ||
+ | | style="background-color:#d9ef8b" |Might have superior OS<sup>1</sup> (secondary endpoint)<br>Median OS: 28.8 vs 23.4 mo<br>(HR 0.71, 95% CI NA-1.03)<br><br>Seems to have superior PFS (primary endpoint)<br>Median PFS: 5.3 vs 4.2 mo<br>(sHR 0.76, 95% CI NA-0.97) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Results are based on a one-sided statistical analysis.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *PRECIOUS: History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this. | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Eribulin (Halaven)]] 1.4 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Pertuzumab (Perjeta)]] as follows: | ||
+ | **Cycle 1: 840 mg IV once on day 1 | ||
+ | **Cycle 2 onwards: 420 mg IV once on day 1 | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''PRECIOUS:''' Yamamoto Y, Iwata H, Taira N, Masuda N, Takahashi M, Yoshinami T, Ueno T, Toyama T, Yamanaka T, Takano T, Kashiwaba M, Tsugawa K, Hasegawa Y, Tamura K, Tada H, Hara F, Fujisawa T, Niikura N, Saji S, Morita S, Toi M, Ohno S. Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS). Cancer Sci. 2022 Sep;113(9):3169-3179. Epub 2022 Jul 23. [https://doi.org/10.1111/cas.15474 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ link to PMC article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/35754298/ PubMed] UMIN000018202 | ||
+ | ==Eribulin & Margetuximab {{#subobject:7mz1b7|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:18op1d|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7823434/ Rugo et al. 2021 (SOPHIA)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-242-1 <span style="color:white;">ESMO-MCBS (2)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2015-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic) | ||
+ | |1a. [[#Eribulin_.26_Trastuzumab|Eribulin & Trastuzumab]]<br>1b. [[#Gemcitabine_.26_Trastuzumab|Gemcitabine & Trastuzumab]]<br>1c. [[#Vinorelbine_.26_Trastuzumab_.28VH.29|VH]]<br>1d. [[#Capecitabine_.26_Trastuzumab_.28XH.29_2|XH]] | ||
+ | | style="background-color:#91cf60" |Seems to have superior PFS (primary endpoint)<br>Median PFS: 6 vs 5 mo<br>(HR 0.76, 95% CI 0.59-0.98)<br><br>Did not meet secondary endpoint of OS<sup>1</sup><br>Median OS: 21.6 vs 21.9 mo<br>(HR 0.95, 95% CI 0.77-1.17) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the 2022 update.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Eribulin (Halaven)]] 1.4 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Margetuximab (Margenza)]] 15 mg/kg IV over 120 minutes once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''SOPHIA:''' Rugo HS, Im SA, Cardoso F, Cortés J, Curigliano G, Musolino A, Pegram MD, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Kaufman B, Yerushalmi R, Fasching PA, Nordstrom JL, Bonvini E, Koenig S, Edlich S, Hong S, Rock EP, Gradishar WJ; SOPHIA Study Group. Efficacy of Margetuximab vs Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Apr 1;7(4):573-584. [https://doi.org/10.1001/jamaoncol.2020.7932 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7823434/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33480963/ PubMed] [https://clinicaltrials.gov/study/NCT02492711 NCT02492711] | ||
+ | ##'''Update:''' Rugo HS, Im SA, Cardoso F, Cortes J, Curigliano G, Musolino A, Pegram MD, Bachelot T, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Schwartz GN, Pluard TJ, Ricci F, Gwin WR 3rd, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Gal-Yam EN, Yerushalmi R, Fasching PA, Kaufman PA, Ashley EJ, Perez-Olle R, Hong S, Rosales MK, Gradishar WJ; SOPHIA Study Group. Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial. J Clin Oncol. 2023 Jan 10;41(2):198-205. Epub 2022 Nov 4. [https://doi.org/10.1200/jco.21.02937 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839304/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839304/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36332179/ PubMed] | ||
+ | ==Eribulin & Trastuzumab {{#subobject:98ug71|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:gh10bb|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7823434/ Rugo et al. 2021 (SOPHIA)] | ||
+ | |2015-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#Capecitabine_.26_Margetuximab|Capecitabine & Margetuximab]]<br>1b. [[#Eribulin_.26_Margetuximab|Eribulin & Margetuximab]]<br>1c. [[#Gemcitabine_.26_Margetuximab|Gemcitabine & Margetuximab]]<br>1d. [[#Vinorelbine_.26_Margetuximab|Vinorelbine & Margetuximab]] | ||
+ | | style="background-color:#fc8d59" |Seems to have inferior PFS | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ Yamamoto et al. 2022 (PRECIOUS)] | ||
+ | |2015-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#THP_.28Docetaxel.29_3|THP (Docetaxel)]]<br>1b. [[#THP_.28Paclitaxel.29|THP (Paclitaxel)]]<br>1c. [[#nab-Paclitaxel.2C_Pertuzumab.2C_Trastuzumab|nab-Paclitaxel, Pertuzumab, Trastuzumab]]<br>1d. [[#VHP|VHP]]<br>1e. [[#EHP|EHP]]<br>1f. [[#XHP|XHP]]<br>1g. [[#GHP|GHP]] | ||
+ | | style="background-color:#fee08b" |Might have inferior OS | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *PRECIOUS: History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this. | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Eribulin (Halaven)]] 1.4 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''SOPHIA:''' Rugo HS, Im SA, Cardoso F, Cortés J, Curigliano G, Musolino A, Pegram MD, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Kaufman B, Yerushalmi R, Fasching PA, Nordstrom JL, Bonvini E, Koenig S, Edlich S, Hong S, Rock EP, Gradishar WJ; SOPHIA Study Group. Efficacy of Margetuximab vs Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Apr 1;7(4):573-584. [https://doi.org/10.1001/jamaoncol.2020.7932 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7823434/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33480963/ PubMed] [https://clinicaltrials.gov/study/NCT02492711 NCT02492711] | ||
+ | ##'''Update:''' Rugo HS, Im SA, Cardoso F, Cortes J, Curigliano G, Musolino A, Pegram MD, Bachelot T, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Schwartz GN, Pluard TJ, Ricci F, Gwin WR 3rd, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Gal-Yam EN, Yerushalmi R, Fasching PA, Kaufman PA, Ashley EJ, Perez-Olle R, Hong S, Rosales MK, Gradishar WJ; SOPHIA Study Group. Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial. J Clin Oncol. 2023 Jan 10;41(2):198-205. Epub 2022 Nov 4. [https://doi.org/10.1200/jco.21.02937 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839304/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36332179/ PubMed] | ||
+ | #'''PRECIOUS:''' Yamamoto Y, Iwata H, Taira N, Masuda N, Takahashi M, Yoshinami T, Ueno T, Toyama T, Yamanaka T, Takano T, Kashiwaba M, Tsugawa K, Hasegawa Y, Tamura K, Tada H, Hara F, Fujisawa T, Niikura N, Saji S, Morita S, Toi M, Ohno S. Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS). Cancer Sci. 2022 Sep;113(9):3169-3179. Epub 2022 Jul 23. [https://doi.org/10.1111/cas.15474 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ link to PMC article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/35754298/ PubMed] UMIN000018202 | ||
+ | ==Gemcitabine & Margetuximab {{#subobject:ugn1b7|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:158gua|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7823434/ Rugo et al. 2021 (SOPHIA)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-242-1 <span style="color:white;">ESMO-MCBS (2)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2015-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic) | ||
+ | |1a. [[#Eribulin_.26_Trastuzumab|Eribulin & Trastuzumab]]<br>1b. [[#Gemcitabine_.26_Trastuzumab|Gemcitabine & Trastuzumab]]<br>1c. [[#Vinorelbine_.26_Trastuzumab_.28VH.29|VH]]<br>1d. [[#Capecitabine_.26_Trastuzumab_.28XH.29_2|XH]] | ||
+ | | style="background-color:#91cf60" |Seems to have superior PFS (primary endpoint)<br>Median PFS: 6 vs 5 mo<br>(HR 0.76, 95% CI 0.59-0.98)<br><br>Did not meet secondary endpoint of OS<sup>1</sup><br>Median OS: 21.6 vs 21.9 mo<br>(HR 0.95, 95% CI 0.77-1.17) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the 2022 update.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Margetuximab (Margenza)]] 15 mg/kg IV over 120 minutes once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''SOPHIA:''' Rugo HS, Im SA, Cardoso F, Cortés J, Curigliano G, Musolino A, Pegram MD, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Kaufman B, Yerushalmi R, Fasching PA, Nordstrom JL, Bonvini E, Koenig S, Edlich S, Hong S, Rock EP, Gradishar WJ; SOPHIA Study Group. Efficacy of Margetuximab vs Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Apr 1;7(4):573-584. [https://doi.org/10.1001/jamaoncol.2020.7932 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7823434/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33480963/ PubMed] [https://clinicaltrials.gov/study/NCT02492711 NCT02492711] | ||
+ | ##'''Update:''' Rugo HS, Im SA, Cardoso F, Cortes J, Curigliano G, Musolino A, Pegram MD, Bachelot T, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Schwartz GN, Pluard TJ, Ricci F, Gwin WR 3rd, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Gal-Yam EN, Yerushalmi R, Fasching PA, Kaufman PA, Ashley EJ, Perez-Olle R, Hong S, Rosales MK, Gradishar WJ; SOPHIA Study Group. Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial. J Clin Oncol. 2023 Jan 10;41(2):198-205. Epub 2022 Nov 4. [https://doi.org/10.1200/jco.21.02937 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839304/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36332179/ PubMed] | ||
+ | ==Gemcitabine & Trastuzumab {{#subobject:981yy2|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, 1000/q3wk trastuzumab {{#subobject:ehgy1b|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7823434/ Rugo et al. 2021 (SOPHIA)] | ||
+ | |2015-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#Capecitabine_.26_Margetuximab|Capecitabine & Margetuximab]]<br>1b. [[#Eribulin_.26_Margetuximab|Eribulin & Margetuximab]]<br>1c. [[#Gemcitabine_.26_Margetuximab|Gemcitabine & Margetuximab]]<br>1d. [[#Vinorelbine_.26_Margetuximab|Vinorelbine & Margetuximab]] | ||
+ | | style="background-color:#fc8d59" |Seems to have inferior PFS | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, 1200/q3wk trastuzumab {{#subobject:ehuigb|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ Yamamoto et al. 2022 (PRECIOUS)] | ||
+ | |2015-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#THP_.28Docetaxel.29_3|THP (Docetaxel)]]<br>1b. [[#THP_.28Paclitaxel.29|THP (Paclitaxel)]]<br>1c. [[#nab-Paclitaxel.2C_Pertuzumab.2C_Trastuzumab|nab-Paclitaxel, Pertuzumab, Trastuzumab]]<br>1d. [[#VHP|VHP]]<br>1e. [[#EHP|EHP]]<br>1f. [[#XHP|XHP]]<br>1g. [[#GHP|GHP]] | ||
+ | | style="background-color:#fee08b" |Might have inferior OS | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *PRECIOUS: History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this. | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Gemcitabine (Gemzar)]] 1200 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #3, weekly trastuzumab {{#subobject:e320bb|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.3816/cbc.2004.n.019 O'Shaughnessy et al. 2004] | ||
+ | |1999-04 to 2001-07 | ||
+ | | style="background-color:#91cf61" |Phase 2 | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Gemcitabine (Gemzar)]] 1200 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15 | ||
+ | **Cycle 2 onwards: 2 mg/kg IV once per day on days 1, 8, 15 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | |||
+ | ===References=== | ||
+ | # O'Shaughnessy JA, Vukelja S, Marsland T, Kimmel G, Ratnam S, Pippen JE. Phase II study of trastuzumab plus gemcitabine in chemotherapy-pretreated patients with metastatic breast cancer. Clin Breast Cancer. 2004 Jun;5(2):142-7. [https://doi.org/10.3816/cbc.2004.n.019 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15245619/ PubMed] | ||
+ | # '''SOPHIA:''' Rugo HS, Im SA, Cardoso F, Cortés J, Curigliano G, Musolino A, Pegram MD, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Kaufman B, Yerushalmi R, Fasching PA, Nordstrom JL, Bonvini E, Koenig S, Edlich S, Hong S, Rock EP, Gradishar WJ; SOPHIA Study Group. Efficacy of Margetuximab vs Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Apr 1;7(4):573-584. [https://doi.org/10.1001/jamaoncol.2020.7932 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7823434/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33480963/ PubMed] [https://clinicaltrials.gov/study/NCT02492711 NCT02492711] | ||
+ | ##'''Update:''' Rugo HS, Im SA, Cardoso F, Cortes J, Curigliano G, Musolino A, Pegram MD, Bachelot T, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Schwartz GN, Pluard TJ, Ricci F, Gwin WR 3rd, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Gal-Yam EN, Yerushalmi R, Fasching PA, Kaufman PA, Ashley EJ, Perez-Olle R, Hong S, Rosales MK, Gradishar WJ; SOPHIA Study Group. Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial. J Clin Oncol. 2023 Jan 10;41(2):198-205. Epub 2022 Nov 4. [https://doi.org/10.1200/jco.21.02937 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839304/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36332179/ PubMed] | ||
+ | #'''PRECIOUS:''' Yamamoto Y, Iwata H, Taira N, Masuda N, Takahashi M, Yoshinami T, Ueno T, Toyama T, Yamanaka T, Takano T, Kashiwaba M, Tsugawa K, Hasegawa Y, Tamura K, Tada H, Hara F, Fujisawa T, Niikura N, Saji S, Morita S, Toi M, Ohno S. Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS). Cancer Sci. 2022 Sep;113(9):3169-3179. Epub 2022 Jul 23. [https://doi.org/10.1111/cas.15474 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ link to PMC article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/35754298/ PubMed] UMIN000018202 | ||
+ | ==GHP {{#subobject:8uve4d|Regimen=1}}== | ||
+ | GHP: '''<u>G</u>'''emcitabine, '''<u>H</u>'''erceptin (Trastuzumab), '''<u>P</u>'''ertuzumab | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:b7d240|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ Yamamoto et al. 2022 (PRECIOUS)] | ||
+ | |2015-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |1a. [[#Docetaxel_.26_Trastuzumab_.28TH.29_4|TH (Docetaxel)]]<br>1b. [[#Paclitaxel_.26_Trastuzumab_.28TH.29_4|TH (Paclitaxel)]]<br>1c. [[#nab-Paclitaxel_.26_Trastuzumab_2|nab-Paclitaxel & Trastuzumab]]<br>1d. [[#Vinorelbine_.26_Trastuzumab_.28VH.29_2|VH]]<br>1e. [[#Eribulin_.26_Trastuzumab|EH]]<br>1f. [[#Capecitabine_.26_Trastuzumab_.28XH.29_2|XH]]<br>1g. [[#Gemcitabine_.26_Trastuzumab|GH]] | ||
+ | | style="background-color:#d9ef8b" |Might have superior OS<sup>1</sup> (secondary endpoint)<br>Median OS: 28.8 vs 23.4 mo<br>(HR 0.71, 95% CI NA-1.03)<br><br>Seems to have superior PFS (primary endpoint)<br>Median PFS: 5.3 vs 4.2 mo<br>(sHR 0.76, 95% CI NA-0.97) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Results are based on a one-sided statistical analysis.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *PRECIOUS: History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this. | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Pertuzumab (Perjeta)]] as follows: | ||
+ | **Cycle 1: 840 mg IV once on day 1 | ||
+ | **Cycle 2 onwards: 420 mg IV once on day 1 | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''PRECIOUS:''' Yamamoto Y, Iwata H, Taira N, Masuda N, Takahashi M, Yoshinami T, Ueno T, Toyama T, Yamanaka T, Takano T, Kashiwaba M, Tsugawa K, Hasegawa Y, Tamura K, Tada H, Hara F, Fujisawa T, Niikura N, Saji S, Morita S, Toi M, Ohno S. Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS). Cancer Sci. 2022 Sep;113(9):3169-3179. Epub 2022 Jul 23. [https://doi.org/10.1111/cas.15474 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ link to PMC article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/35754298/ PubMed] UMIN000018202 | ||
+ | ==Lapatinib & Trastuzumab {{#subobject:9be4d2|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:e892bb|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2008.21.4437 Blackwell et al. 2010 (EGF104900)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-5-1 <span style="color:white;">ESMO-MCBS (4)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2005-11 to 2006-11 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |[[Breast_cancer,_HER2-positive_-_historical#Lapatinib_monotherapy|Lapatinib]] | ||
+ | | style="background-color:#1a9850" |Superior PFS<sup>1</sup> (primary endpoint)<br>Median PFS: 11.1 vs 8.1 weeks<br>(HR 0.74, 95% CI 0.58-0.94)<br><br>Seems to have superior OS<sup>1</sup> (secondary endpoint)<br>Median OS: 14 vs 9.5 mo<br>(HR 0.74, 95% CI 0.57-0.97) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the 2012 update.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Lapatinib (Tykerb)]] 1000 mg PO once per day on days 1 to 7 | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 4 mg/kg IV once on day 1, | ||
+ | **Cycle 2 onwards: 2 mg/kg IV once on day 1 | ||
+ | '''7-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | <!-- Presented in part at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL, and the 33rd Annual Meeting of the European Society for Medical Oncology, September 12-16, 2008, Stockholm, Sweden. --> | ||
+ | # '''EGF104900:''' Blackwell KL, Burstein HJ, Storniolo AM, Rugo H, Sledge G, Koehler M, Ellis C, Casey M, Vukelja S, Bischoff J, Baselga J, O'Shaughnessy J. Randomized study of Lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol. 2010 Mar 1;28(7):1124-30. Epub 2010 Feb 1. [https://doi.org/10.1200/jco.2008.21.4437 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20124187/ PubMed] [https://clinicaltrials.gov/study/NCT00320385 NCT00320385] | ||
+ | ## '''Update:''' Blackwell KL, Burstein HJ, Storniolo AM, Rugo HS, Sledge G, Aktan G, Ellis C, Florance A, Vukelja S, Bischoff J, Baselga J, O'Shaughnessy J. Overall survival benefit with lapatinib in combination with trastuzumab for patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: final results from the EGF104900 Study. J Clin Oncol. 2012 Jul 20;30(21):2585-92. Epub 2012 Jun 11. [https://doi.org/10.1200/jco.2011.35.6725 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22689807/ PubMed] | ||
+ | |||
+ | ==Paclitaxel & Trastuzumab (TH) {{#subobject:aahu8e|Regimen=1}}== | ||
+ | TH: '''<u>T</u>'''axol (Paclitaxel), '''<u>H</u>'''erceptin (Trastuzumab) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:d7ugbv|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ Yamamoto et al. 2022 (PRECIOUS)] | ||
+ | |2015-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#THP_.28Docetaxel.29_3|THP (Docetaxel)]]<br>1b. [[#THP_.28Paclitaxel.29|THP (Paclitaxel)]]<br>1c. [[#nab-Paclitaxel.2C_Pertuzumab.2C_Trastuzumab|nab-Paclitaxel, Pertuzumab, Trastuzumab]]<br>1d. [[#VHP|VHP]]<br>1e. [[#EHP|EHP]]<br>1f. [[#XHP|XHP]]<br>1g. [[#GHP|GHP]] | ||
+ | | style="background-color:#fee08b" |Might have inferior OS | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''PRECIOUS:''' Yamamoto Y, Iwata H, Taira N, Masuda N, Takahashi M, Yoshinami T, Ueno T, Toyama T, Yamanaka T, Takano T, Kashiwaba M, Tsugawa K, Hasegawa Y, Tamura K, Tada H, Hara F, Fujisawa T, Niikura N, Saji S, Morita S, Toi M, Ohno S. Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS). Cancer Sci. 2022 Sep;113(9):3169-3179. Epub 2022 Jul 23. [https://doi.org/10.1111/cas.15474 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ link to PMC article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/35754298/ PubMed] UMIN000018202 | ||
+ | ==Paclitaxel, Pertuzumab, Trastuzumab emtansine {{#subobject:bjc7e1|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, q3wk T-DM1 {{#subobject:18ba4d|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791863/ Krop et al. 2016 (TDM4652g)] | ||
+ | |2009 to not reported | ||
+ | |style="background-color:#91cf61"|Phase 1b/2a | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: this is the MTD.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Pertuzumab (Perjeta)]] as follows: | ||
+ | **Cycle 1: 840 mg IV once on day 1 | ||
+ | **Cycle 2 onwards: 420 mg IV once on day 1 | ||
+ | ====Antibody-drug conjugate therapy==== | ||
+ | *[[Trastuzumab emtansine (Kadcyla)]] 3.6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, weekly T-DM1 {{#subobject:18hb4d|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791863/ Krop et al. 2016 (TDM4652g)] | ||
+ | |2009 to not reported | ||
+ | |style="background-color:#91cf61"|Phase 1b/2a | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: this is the MTD.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Pertuzumab (Perjeta)]] as follows: | ||
+ | **Cycle 1: 840 mg IV once on day 1 | ||
+ | **Cycle 2 onwards: 420 mg IV once on day 1 | ||
+ | ====Antibody-drug conjugate therapy==== | ||
+ | *[[Trastuzumab emtansine (Kadcyla)]] 2.4 mg/kg IV once per day on days 1, 8, 15 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''TDM4652g:''' Krop IE, Modi S, LoRusso PM, Pegram M, Guardino E, Althaus B, Lu D, Strasak A, Elias A. Phase 1b/2a study of trastuzumab emtansine (T-DM1), paclitaxel, and pertuzumab in HER2-positive metastatic breast cancer. Breast Cancer Res. 2016 Mar 15;18(1):34. [https://doi.org/10.1186/s13058-016-0691-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791863/ link to PMC article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26979312/ PubMed] | ||
+ | ==nab-Paclitaxel & Trastuzumab {{#subobject:au1u8e|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1 {{#subobject:jg9bzv|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ Yamamoto et al. 2022 (PRECIOUS)] | ||
+ | |2015-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#THP_.28Docetaxel.29_3|THP (Docetaxel)]]<br>1b. [[#THP_.28Paclitaxel.29|THP (Paclitaxel)]]<br>1c. [[#nab-Paclitaxel.2C_Pertuzumab.2C_Trastuzumab|nab-Paclitaxel, Pertuzumab, Trastuzumab]]<br>1d. [[#VHP|VHP]]<br>1e. [[#EHP|EHP]]<br>1f. [[#XHP|XHP]]<br>1g. [[#GHP|GHP]] | ||
+ | | style="background-color:#fee08b" |Might have inferior OS | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 220 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2 {{#subobject:jgkssv|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ Yamamoto et al. 2022 (PRECIOUS)] | ||
+ | |2015-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#THP_.28Docetaxel.29_3|THP (Docetaxel)]]<br>1b. [[#THP_.28Paclitaxel.29|THP (Paclitaxel)]]<br>1c. [[#nab-Paclitaxel.2C_Pertuzumab.2C_Trastuzumab|nab-Paclitaxel, Pertuzumab, Trastuzumab]]<br>1d. [[#VHP|VHP]]<br>1e. [[#EHP|EHP]]<br>1f. [[#XHP|XHP]]<br>1g. [[#GHP|GHP]] | ||
+ | | style="background-color:#fee08b" |Might have inferior OS | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 260 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''PRECIOUS:''' Yamamoto Y, Iwata H, Taira N, Masuda N, Takahashi M, Yoshinami T, Ueno T, Toyama T, Yamanaka T, Takano T, Kashiwaba M, Tsugawa K, Hasegawa Y, Tamura K, Tada H, Hara F, Fujisawa T, Niikura N, Saji S, Morita S, Toi M, Ohno S. Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS). Cancer Sci. 2022 Sep;113(9):3169-3179. Epub 2022 Jul 23. [https://doi.org/10.1111/cas.15474 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ link to PMC article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/35754298/ PubMed] UMIN000018202 | ||
+ | ==nab-Paclitaxel, Pertuzumab, Trastuzumab {{#subobject:ajbxr9|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1 {{#subobject:1utgxq|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ Yamamoto et al. 2022 (PRECIOUS)] | ||
+ | |2015-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |1a. [[#Docetaxel_.26_Trastuzumab_.28TH.29_4|TH (Docetaxel)]]<br>1b. [[#Paclitaxel_.26_Trastuzumab_.28TH.29_4|TH (Paclitaxel)]]<br>1c. [[#nab-Paclitaxel_.26_Trastuzumab_2|nab-Paclitaxel & Trastuzumab]]<br>1d. [[#Vinorelbine_.26_Trastuzumab_.28VH.29_2|VH]]<br>1e. [[#Eribulin_.26_Trastuzumab|EH]]<br>1f. [[#Capecitabine_.26_Trastuzumab_.28XH.29_2|XH]]<br>1g. [[#Gemcitabine_.26_Trastuzumab|GH]] | ||
+ | | style="background-color:#d9ef8b" |Might have superior OS<sup>1</sup> (secondary endpoint)<br>Median OS: 28.8 vs 23.4 mo<br>(HR 0.71, 95% CI NA-1.03)<br><br>Seems to have superior PFS (primary endpoint)<br>Median PFS: 5.3 vs 4.2 mo<br>(sHR 0.76, 95% CI NA-0.97) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Results are based on a one-sided statistical analysis.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *PRECIOUS: History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this. | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 220 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Pertuzumab (Perjeta)]] as follows: | ||
+ | **Cycle 1: 840 mg IV once on day 1 | ||
+ | **Cycle 2 onwards: 420 mg IV once on day 1 | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2 {{#subobject:1ut854|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ Yamamoto et al. 2022 (PRECIOUS)] | ||
+ | |2015-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |1a. [[#Docetaxel_.26_Trastuzumab_.28TH.29_4|TH (Docetaxel)]]<br>1b. [[#Paclitaxel_.26_Trastuzumab_.28TH.29_4|TH (Paclitaxel)]]<br>1c. [[#nab-Paclitaxel_.26_Trastuzumab_2|nab-Paclitaxel & Trastuzumab]]<br>1d. [[#Vinorelbine_.26_Trastuzumab_.28VH.29_2|VH]]<br>1e. [[#Eribulin_.26_Trastuzumab|EH]]<br>1f. [[#Capecitabine_.26_Trastuzumab_.28XH.29_2|XH]]<br>1g. [[#Gemcitabine_.26_Trastuzumab|GH]] | ||
+ | | style="background-color:#d9ef8b" |Might have superior OS<sup>1</sup> (secondary endpoint)<br>Median OS: 28.8 vs 23.4 mo<br>(HR 0.71, 95% CI NA-1.03)<br><br>Seems to have superior PFS (primary endpoint)<br>Median PFS: 5.3 vs 4.2 mo<br>(sHR 0.76, 95% CI NA-0.97) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Results are based on a one-sided statistical analysis.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *PRECIOUS: History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this. | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 260 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Pertuzumab (Perjeta)]] as follows: | ||
+ | **Cycle 1: 840 mg IV once on day 1 | ||
+ | **Cycle 2 onwards: 420 mg IV once on day 1 | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''PRECIOUS:''' Yamamoto Y, Iwata H, Taira N, Masuda N, Takahashi M, Yoshinami T, Ueno T, Toyama T, Yamanaka T, Takano T, Kashiwaba M, Tsugawa K, Hasegawa Y, Tamura K, Tada H, Hara F, Fujisawa T, Niikura N, Saji S, Morita S, Toi M, Ohno S. Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS). Cancer Sci. 2022 Sep;113(9):3169-3179. Epub 2022 Jul 23. [https://doi.org/10.1111/cas.15474 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ link to PMC article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/35754298/ PubMed] UMIN000018202 | ||
+ | ==Pertuzumab & Trastuzumab {{#subobject:b1d7b1|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, q3wk trastuzumab {{#subobject:4f5a4d|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979216/ Baselga et al. 2010 (NCI-P6660)] | ||
+ | |2005 to not reported | ||
+ | |style="background-color:#91cf61"|Phase 2 | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Pertuzumab (Perjeta)]] as follows, '''given second''': | ||
+ | **Cycle 1: 840 mg IV once on day 2 | ||
+ | **Cycle 2 onwards: 420 mg IV once on day 1 | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Loading dose: 8 mg/kg IV once on day -28 (that is, 28 days before the start of cycle 1) | ||
+ | **Cycle 1 onwards: 6 mg/kg IV once on day 1, '''given first''' | ||
+ | '''21-day cycle for 8 cycles''' | ||
+ | ''Treatment can be continued if there is no progressive disease.'' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, weekly trastuzumab {{#subobject:ecb953|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979216/ Baselga et al. 2010 (NCI-P6660)] | ||
+ | |2005 to not reported | ||
+ | |style="background-color:#91cf61"|Phase 2 | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Pertuzumab (Perjeta)]] '''given second''' as follows: | ||
+ | **Cycle 1: 840 mg IV once on day 2 | ||
+ | **Cycles 2 to 8: 420 mg IV once on day 1 | ||
+ | *[[Trastuzumab (Herceptin)]] '''given first''' as follows: | ||
+ | **Cycle 0: 4 mg/kg IV once on day -28 (that is, 28 days before the start of cycle 1) | ||
+ | **Cycles 1 to 8: 2 mg/kg IV once per day on days 1, 8, 15 | ||
+ | '''21-day cycle for 8 cycles'''; treatment can be continued if there is no progressive disease | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''NCI-P6660:''' Baselga J, Gelmon KA, Verma S, Wardley A, Conte P, Miles D, Bianchi G, Cortes J, McNally VA, Ross GA, Fumoleau P, Gianni L. Phase II trial of pertuzumab and trastuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer that progressed during prior trastuzumab therapy. J Clin Oncol. 2010 Mar 1;28(7):1138-44. Epub 2010 Feb 1. [https://doi.org/10.1200/jco.2009.24.2024 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979216/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20124182/ PubMed] [https://clinicaltrials.gov/study/NCT00301899 NCT00301899] | ||
+ | ==THP (Docetaxel) {{#subobject:agcb69|Regimen=1}}== | ||
+ | THP: '''<u>T</u>'''axotere (Docetaxel), '''<u>H</u>'''erceptin (Trastuzumab), '''<u>P</u>'''ertuzumab | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1 {{#subobject:1ub3dc|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ Yamamoto et al. 2022 (PRECIOUS)] | ||
+ | |2015-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |1a. [[#Docetaxel_.26_Trastuzumab_.28TH.29_4|TH (Docetaxel)]]<br>1b. [[#Paclitaxel_.26_Trastuzumab_.28TH.29_4|TH (Paclitaxel)]]<br>1c. [[#nab-Paclitaxel_.26_Trastuzumab_2|nab-Paclitaxel & Trastuzumab]]<br>1d. [[#Vinorelbine_.26_Trastuzumab_.28VH.29_2|VH]]<br>1e. [[#Eribulin_.26_Trastuzumab|EH]]<br>1f. [[#Capecitabine_.26_Trastuzumab_.28XH.29_2|XH]]<br>1g. [[#Gemcitabine_.26_Trastuzumab|GH]] | ||
+ | | style="background-color:#d9ef8b" |Might have superior OS<sup>1</sup> (secondary endpoint)<br>Median OS: 28.8 vs 23.4 mo<br>(HR 0.71, 95% CI NA-1.03)<br><br>Seems to have superior PFS (primary endpoint)<br>Median PFS: 5.3 vs 4.2 mo<br>(sHR 0.76, 95% CI NA-0.97) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Results are based on a one-sided statistical analysis.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *PRECIOUS: History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this. | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Pertuzumab (Perjeta)]] as follows: | ||
+ | **Cycle 1: 840 mg IV once on day 1 | ||
+ | **Cycle 2 onwards: 420 mg IV once on day 1 | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2 {{#subobject:jhrrsv|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ Yamamoto et al. 2022 (PRECIOUS)] | ||
+ | |2015-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |1a. [[#Docetaxel_.26_Trastuzumab_.28TH.29_4|TH (Docetaxel)]]<br>1b. [[#Paclitaxel_.26_Trastuzumab_.28TH.29_4|TH (Paclitaxel)]]<br>1c. [[#nab-Paclitaxel_.26_Trastuzumab_2|nab-Paclitaxel & Trastuzumab]]<br>1d. [[#Vinorelbine_.26_Trastuzumab_.28VH.29_2|VH]]<br>1e. [[#Eribulin_.26_Trastuzumab|EH]]<br>1f. [[#Capecitabine_.26_Trastuzumab_.28XH.29_2|XH]]<br>1g. [[#Gemcitabine_.26_Trastuzumab|GH]] | ||
+ | | style="background-color:#d9ef8b" |Might have superior OS<sup>1</sup> (secondary endpoint)<br>Median OS: 28.8 vs 23.4 mo<br>(HR 0.71, 95% CI NA-1.03)<br><br>Seems to have superior PFS (primary endpoint)<br>Median PFS: 5.3 vs 4.2 mo<br>(sHR 0.76, 95% CI NA-0.97) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Results are based on a one-sided statistical analysis.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *PRECIOUS: History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this. | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Pertuzumab (Perjeta)]] as follows: | ||
+ | **Cycle 1: 840 mg IV once on day 1 | ||
+ | **Cycle 2 onwards: 420 mg IV once on day 1 | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''PRECIOUS:''' Yamamoto Y, Iwata H, Taira N, Masuda N, Takahashi M, Yoshinami T, Ueno T, Toyama T, Yamanaka T, Takano T, Kashiwaba M, Tsugawa K, Hasegawa Y, Tamura K, Tada H, Hara F, Fujisawa T, Niikura N, Saji S, Morita S, Toi M, Ohno S. Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS). Cancer Sci. 2022 Sep;113(9):3169-3179. Epub 2022 Jul 23. [https://doi.org/10.1111/cas.15474 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ link to PMC article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/35754298/ PubMed] UMIN000018202 | ||
+ | ==THP (Paclitaxel) {{#subobject:aggcc9|Regimen=1}}== | ||
+ | THP: '''<u>T</u>'''axol (Paclitaxel), '''<u>H</u>'''erceptin (Trastuzumab), '''<u>P</u>'''ertuzumab | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:1uioqq|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ Yamamoto et al. 2022 (PRECIOUS)] | ||
+ | |2015-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |1a. [[#Docetaxel_.26_Trastuzumab_.28TH.29_4|TH (Docetaxel)]]<br>1b. [[#Paclitaxel_.26_Trastuzumab_.28TH.29_4|TH (Paclitaxel)]]<br>1c. [[#nab-Paclitaxel_.26_Trastuzumab_2|nab-Paclitaxel & Trastuzumab]]<br>1d. [[#Vinorelbine_.26_Trastuzumab_.28VH.29_2|VH]]<br>1e. [[#Eribulin_.26_Trastuzumab|EH]]<br>1f. [[#Capecitabine_.26_Trastuzumab_.28XH.29_2|XH]]<br>1g. [[#Gemcitabine_.26_Trastuzumab|GH]] | ||
+ | | style="background-color:#d9ef8b" |Might have superior OS<sup>1</sup> (secondary endpoint)<br>Median OS: 28.8 vs 23.4 mo<br>(HR 0.71, 95% CI NA-1.03)<br><br>Seems to have superior PFS (primary endpoint)<br>Median PFS: 5.3 vs 4.2 mo<br>(sHR 0.76, 95% CI NA-0.97) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Results are based on a one-sided statistical analysis.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *PRECIOUS: History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this. | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Pertuzumab (Perjeta)]] as follows: | ||
+ | **Cycle 1: 840 mg IV once on day 1 | ||
+ | **Cycle 2 onwards: 420 mg IV once on day 1 | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''PRECIOUS:''' Yamamoto Y, Iwata H, Taira N, Masuda N, Takahashi M, Yoshinami T, Ueno T, Toyama T, Yamanaka T, Takano T, Kashiwaba M, Tsugawa K, Hasegawa Y, Tamura K, Tada H, Hara F, Fujisawa T, Niikura N, Saji S, Morita S, Toi M, Ohno S. Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS). Cancer Sci. 2022 Sep;113(9):3169-3179. Epub 2022 Jul 23. [https://doi.org/10.1111/cas.15474 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ link to PMC article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/35754298/ PubMed] UMIN000018202 | ||
+ | ==Trastuzumab monotherapy {{#subobject:9ugha2|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:1ac44u|Variant=1}}=== | ||
+ | {| class="wikitable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.1999.17.9.2639 Cobleigh et al. 1999] | ||
+ | |1995-04 to 1996-09 | ||
+ | | style="background-color:#91cf61" |Phase 2 (RT) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 4 mg/kg IV over 90 minutes once on day 1 | ||
+ | **Cycle 2 onwards: 2 mg/kg IV over 30 minutes once on day 1 | ||
+ | '''7-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # Cobleigh MA, Vogel CL, Tripathy D, Robert NJ, Scholl S, Fehrenbacher L, Wolter JM, Paton V, Shak S, Lieberman G, Slamon DJ. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol. 1999 Sep;17(9):2639-48. [https://doi.org/10.1200/JCO.1999.17.9.2639 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10561337/ PubMed] | ||
+ | |||
+ | ==Trastuzumab deruxtecan monotherapy {{#subobject:d2616v|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:d4fac1|Variant=1}}=== | ||
+ | {| class="wikitable" style="color:white; background-color:#404040" | ||
+ | |<small>'''FDA-recommended dose'''</small> | ||
+ | |- | ||
+ | |} | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7458671/ Modi et al. 2019 (DESTINY-Breast01)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-164-1 <span style="color:white;">ESMO-MCBS (2)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2017-2018 | ||
+ | | style="background-color:#91cf61" |Phase 2 (RT) | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/nejmoa2115022 Cortés et al. 2022 (DESTINY-Breast03)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-342-1 <span style="color:white;">ESMO-MCBS (3)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2018-2020 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-RT-switch-ic) | ||
+ | |[[#Trastuzumab_emtansine_monotherapy_3|T-DM1]] | ||
+ | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>PFS12: 75.8% vs 34.1%<br>(HR 0.28, 95% CI 0.22-0.37)<br><br>Superior OS<sup>1</sup> (secondary endpoint)<br>Median OS: NYR vs NYR<br>(HR 0.64, 95% CI 0.47-0.87) | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/s0140-6736(23)00725-0 André et al. 2023 (DESTINY-Breast02)] | ||
+ | |2018-09-06 to 2020-12-31 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | ||
+ | |Investigator's choice of:<br>1a. [[#Capecitabine_.26_Lapatinib_2|Capecitabine & Lapatinib]]<br>1b. [[#Capecitabine_.26_Trastuzumab_.28XH.29_2|XH]] | ||
+ | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 17.8 vs 6.9 mo<br>(HR 0.36, 95% CI 0.28-0.45) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the 2022 update.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *DESTINY-Breast01 & DESTINY-Breast02: Refractory to trastuzumab emtansine | ||
+ | *DESTINY-Breast03: Trastuzumab and taxane | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Antibody-drug conjugate therapy==== | ||
+ | *[[Trastuzumab deruxtecan (Enhertu)]] 5.4 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''DESTINY-Breast01:''' Modi S, Saura C, Yamashita T, Park YH, Kim SB, Tamura K, Andre F, Iwata H, Ito Y, Tsurutani J, Sohn J, Denduluri N, Perrin C, Aogi K, Tokunaga E, Im SA, Lee KS, Hurvitz SA, Cortes J, Lee C, Chen S, Zhang L, Shahidi J, Yver A, Krop I; DESTINY-Breast01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. N Engl J Med. 2020 Feb 13;382(7):610-621. Epub 2019 Dec 11. [https://doi.org/10.1056/NEJMoa1914510 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7458671/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31825192/ PubMed] [https://clinicaltrials.gov/study/NCT03248492 NCT03248492] | ||
+ | ##'''Update:''' Saura C, Modi S, Krop I, Park YH, Kim SB, Tamura K, Iwata H, Tsurutani J, Sohn J, Mathias E, Liu Y, Cathcart J, Singh J, Yamashita T. Trastuzumab deruxtecan in previously treated patients with HER2-positive metastatic breast cancer: updated survival results from a phase II trial (DESTINY-Breast01). Ann Oncol. 2024 Mar;35(3):302-307. Epub 2023 Dec 11. [https://doi.org/10.1016/j.annonc.2023.12.001 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38092229/ PubMed] | ||
+ | # '''DESTINY-Breast03:''' Cortés J, Kim SB, Chung WP, Im SA, Park YH, Hegg R, Kim MH, Tseng LM, Petry V, Chung CF, Iwata H, Hamilton E, Curigliano G, Xu B, Huang CS, Kim JH, Chiu JWY, Pedrini JL, Lee C, Liu Y, Cathcart J, Bako E, Verma S, Hurvitz SA; DESTINY-Breast03 Trial Investigators. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med. 2022 Mar 24;386(12):1143-1154. [https://doi.org/10.1056/nejmoa2115022 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/35320644/ PubMed] [https://clinicaltrials.gov/study/NCT03529110 NCT03529110] | ||
+ | ##'''Update:''' Hurvitz SA, Hegg R, Chung WP, Im SA, Jacot W, Ganju V, Chiu JWY, Xu B, Hamilton E, Madhusudan S, Iwata H, Altintas S, Henning JW, Curigliano G, Perez-Garcia JM, Kim SB, Petry V, Huang CS, Li W, Frenel JS, Antolin S, Yeo W, Bianchini G, Loi S, Tsurutani J, Egorov A, Liu Y, Cathcart J, Ashfaque S, Cortés J. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. Lancet. 2023 Jan 14;401(10371):105-117. Epub 2022 Dec 7. [https://doi.org/10.1016/s0140-6736(22)02420-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36495879/ PubMed] | ||
+ | ##'''PRO analysis:''' Curigliano G, Dunton K, Rosenlund M, Janek M, Cathcart J, Liu Y, Fasching PA, Iwata H. Patient-reported outcomes and hospitalization data in patients with HER2-positive metastatic breast cancer receiving trastuzumab deruxtecan or trastuzumab emtansine in the phase III DESTINY-Breast03 study. Ann Oncol. 2023 Jul;34(7):569-577. Epub 2023 May 12. [https://doi.org/10.1016/j.annonc.2023.04.516 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37179020/ PubMed] | ||
+ | ##'''Subgroup analysis:''' Hurvitz SA, Kim SB, Chung WP, Im SA, Park YH, Hegg R, Kim MH, Tseng LM, Petry V, Chung CF, Iwata H, Hamilton E, Curigliano G, Xu B, Egorov A, Liu Y, Cathcart J, Bako E, Tecson K, Verma S, Cortés J. Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer patients with brain metastases from the randomized DESTINY-Breast03 trial. ESMO Open. 2024 May;9(5):102924. Epub 2024 Apr 24. [https://doi.org/10.1016/j.esmoop.2024.102924 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11145752/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/38796287/ PubMed] | ||
+ | #'''DESTINY-Breast02:''' André F, Hee Park Y, Kim SB, Takano T, Im SA, Borges G, Lima JP, Aksoy S, Gavila Gregori J, De Laurentiis M, Bianchini G, Roylance R, Miyoshi Y, Armstrong A, Sinha R, Ruiz Borrego M, Lim E, Ettl J, Yerushalmi R, Zagouri F, Duhoux FP, Fehm T, Gambhire D, Cathcart J, Wu C, Chu C, Egorov A, Krop I. Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2023 May 27;401(10390):1773-1785. Epub 2023 Apr 20. [https://doi.org/10.1016/s0140-6736(23)00725-0 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/37086745/ PubMed] [https://clinicaltrials.gov/study/NCT03523585 NCT03523585] | ||
+ | ##'''PRO analysis:''' Fehm T, Cottone F, Dunton K, André F, Krop I, Park YH, De Laurentiis M, Miyoshi Y, Armstrong A, Borrego MR, Yerushalmi R, Duhoux FP, Takano T, Lu W, Egorov A, Kim SB. Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): patient-reported outcomes from a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2024 May;25(5):614-625. [https://doi.org/10.1016/s1470-2045(24)00128-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38697155/ PubMed] | ||
+ | |||
+ | ==Trastuzumab emtansine monotherapy {{#subobject:d260e0|Regimen=1}}== | ||
+ | T-DM1: '''<u>T</u>'''rastuzumab-'''<u>DM1</u>''' (Trastuzumab emtansine) | ||
+ | ===Example orders=== | ||
+ | *[[Example orders for trastuzumab emtansine (Kadcyla) in breast cancer]] | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:d42e82|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125250/ Verma et al. 2012 (EMILIA)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-3-1 <span style="color:white;">ESMO-MCBS (4)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2009-2011 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-RT-switch-ooc) | ||
+ | |[[#Capecitabine_.26_Lapatinib_2|Capecitabine & Lapatinib]] | ||
+ | |style="background-color:#1a9850"|Superior OS<sup>1</sup> (co-primary endpoint)<br>Median OS: 29.9 vs 25.9 mo<br>(HR 0.75, 95% CI 0.64-0.88) | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S1470-2045(14)70178-0 Krop et al. 2014 (TH3RESA)] | ||
+ | |2011-09-14 to 2012-11-19 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-switch-ooc) | ||
+ | |Physician's choice | ||
+ | |style="background-color:#1a9850"|Superior OS<sup>2</sup> (co-primary endpoint)<br>Median OS: 22.7 vs 15.8 mo<br>(HR 0.68, 95% CI 0.54-0.85) | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/nejmoa2115022 Cortés et al. 2022 (DESTINY-Breast03)] | ||
+ | |2018-2020 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#Trastuzumab_deruxtecan_monotherapy|Trastuzumab deruxtecan]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Reported efficacy for EMILIA is based on the 2017 update.''<br> | ||
+ | ''<sup>2</sup>Reported efficacy for TH3RESA is based on the 2017 update.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Antibody-drug conjugate therapy==== | ||
+ | *[[Trastuzumab emtansine (Kadcyla)]] 3.6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''EMILIA:''' Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh DY, Diéras V, Guardino E, Fang L, Lu MW, Olsen S, Blackwell K; EMILIA Study Group. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012 Nov 8;367(19):1783-91. Epub 2012 Oct 1. Erratum in: N Engl J Med. 2013 Jun 20;368(25):2442. [https://doi.org/10.1056/NEJMoa1209124 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125250/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23020162/ PubMed] [https://clinicaltrials.gov/study/NCT00829166 NCT00829166] | ||
+ | ## '''PRO analysis:''' Welslau M, Diéras V, Sohn JH, Hurvitz SA, Lalla D, Fang L, Althaus B, Guardino E, Miles D. Patient-reported outcomes from EMILIA, a randomized phase 3 study of trastuzumab emtansine (T-DM1) versus capecitabine and lapatinib in human epidermal growth factor receptor 2-positive locally advanced or metastatic breast cancer. Cancer. 2014 Mar 1;120(5):642-51. Epub 2013 Nov 12. [https://doi.org/10.1002/cncr.28465 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24222194/ PubMed] | ||
+ | ## '''Update:''' Diéras V, Miles D, Verma S, Pegram M, Welslau M, Baselga J, Krop IE, Blackwell K, Hoersch S, Xu J, Green M, Gianni L. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2017 Jun;18(6):732-742. Epub 2017 May 16. [https://doi.org/10.1016/S1470-2045(17)30312-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5531181/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28526536/ PubMed] | ||
+ | # '''TH3RESA:''' Krop IE, Kim SB, González-Martín A, LoRusso PM, Ferrero JM, Smitt M, Yu R, Leung AC, Wildiers H; TH3RESA study collaborators. Trastuzumab emtansine versus treatment of physician's choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014 Jun;15(7):689-99. Epub 2014 May 2. [https://doi.org/10.1016/S1470-2045(14)70178-0 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24793816/ PubMed] [https://clinicaltrials.gov/study/NCT01419197 NCT01419197] | ||
+ | ## '''Update:''' Krop IE, Kim SB, Martin AG, LoRusso PM, Ferrero JM, Badovinac-Crnjevic T, Hoersch S, Smitt M, Wildiers H. Trastuzumab emtansine versus treatment of physician's choice in patients with previously treated HER2-positive metastatic breast cancer (TH3RESA): final overall survival results from a randomised open-label phase 3 trial. Lancet Oncol. 2017 Jun;18(6):743-754. Epub 2017 May 16. [https://doi.org/10.1016/S1470-2045(17)30313-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28526538/ PubMed] | ||
+ | # '''DESTINY-Breast03:''' Cortés J, Kim SB, Chung WP, Im SA, Park YH, Hegg R, Kim MH, Tseng LM, Petry V, Chung CF, Iwata H, Hamilton E, Curigliano G, Xu B, Huang CS, Kim JH, Chiu JWY, Pedrini JL, Lee C, Liu Y, Cathcart J, Bako E, Verma S, Hurvitz SA; DESTINY-Breast03 Trial Investigators. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med. 2022 Mar 24;386(12):1143-1154. [https://doi.org/10.1056/nejmoa2115022 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/35320644/ PubMed] [https://clinicaltrials.gov/study/NCT03529110 NCT03529110] | ||
+ | ##'''Update:''' Hurvitz SA, Hegg R, Chung WP, Im SA, Jacot W, Ganju V, Chiu JWY, Xu B, Hamilton E, Madhusudan S, Iwata H, Altintas S, Henning JW, Curigliano G, Perez-Garcia JM, Kim SB, Petry V, Huang CS, Li W, Frenel JS, Antolin S, Yeo W, Bianchini G, Loi S, Tsurutani J, Egorov A, Liu Y, Cathcart J, Ashfaque S, Cortés J. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. Lancet. 2023 Jan 14;401(10371):105-117. Epub 2022 Dec 7. [https://doi.org/10.1016/s0140-6736(22)02420-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36495879/ PubMed] | ||
+ | ##'''PRO analysis:''' Curigliano G, Dunton K, Rosenlund M, Janek M, Cathcart J, Liu Y, Fasching PA, Iwata H. Patient-reported outcomes and hospitalization data in patients with HER2-positive metastatic breast cancer receiving trastuzumab deruxtecan or trastuzumab emtansine in the phase III DESTINY-Breast03 study. Ann Oncol. 2023 Jul;34(7):569-577. Epub 2023 May 12. [https://doi.org/10.1016/j.annonc.2023.04.516 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37179020/ PubMed] | ||
+ | ##'''Subgroup analysis:''' Hurvitz SA, Kim SB, Chung WP, Im SA, Park YH, Hegg R, Kim MH, Tseng LM, Petry V, Chung CF, Iwata H, Hamilton E, Curigliano G, Xu B, Egorov A, Liu Y, Cathcart J, Bako E, Tecson K, Verma S, Cortés J. Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer patients with brain metastases from the randomized DESTINY-Breast03 trial. ESMO Open. 2024 May;9(5):102924. Epub 2024 Apr 24. [https://doi.org/10.1016/j.esmoop.2024.102924 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11145752/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/38796287/ PubMed] | ||
+ | ==Vinorelbine & Margetuximab {{#subobject:96tyn7|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:15dbhj|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7823434/ Rugo et al. 2021 (SOPHIA)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-242-1 <span style="color:white;">ESMO-MCBS (2)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2015-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic) | ||
+ | |1a. [[#Eribulin_.26_Trastuzumab|Eribulin & Trastuzumab]]<br>1b. [[#Gemcitabine_.26_Trastuzumab|Gemcitabine & Trastuzumab]]<br>1c. [[#Vinorelbine_.26_Trastuzumab_.28VH.29|VH]]<br>1d. [[#Capecitabine_.26_Trastuzumab_.28XH.29_2|XH]] | ||
+ | | style="background-color:#91cf60" |Seems to have superior PFS (primary endpoint)<br>Median PFS: 6 vs 5 mo<br>(HR 0.76, 95% CI 0.59-0.98)<br><br>Did not meet secondary endpoint of OS<sup>1</sup><br>Median OS: 21.6 vs 21.9 mo<br>(HR 0.95, 95% CI 0.77-1.17) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the 2022 update.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Vinorelbine (Navelbine)]] 25 to 30 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Margetuximab (Margenza)]] 15 mg/kg IV over 120 minutes once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''SOPHIA:''' Rugo HS, Im SA, Cardoso F, Cortés J, Curigliano G, Musolino A, Pegram MD, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Kaufman B, Yerushalmi R, Fasching PA, Nordstrom JL, Bonvini E, Koenig S, Edlich S, Hong S, Rock EP, Gradishar WJ; SOPHIA Study Group. Efficacy of Margetuximab vs Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Apr 1;7(4):573-584. [https://doi.org/10.1001/jamaoncol.2020.7932 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7823434/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33480963/ PubMed] [https://clinicaltrials.gov/study/NCT02492711 NCT02492711] | ||
+ | ##'''Update:''' Rugo HS, Im SA, Cardoso F, Cortes J, Curigliano G, Musolino A, Pegram MD, Bachelot T, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Schwartz GN, Pluard TJ, Ricci F, Gwin WR 3rd, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Gal-Yam EN, Yerushalmi R, Fasching PA, Kaufman PA, Ashley EJ, Perez-Olle R, Hong S, Rosales MK, Gradishar WJ; SOPHIA Study Group. Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial. J Clin Oncol. 2023 Jan 10;41(2):198-205. Epub 2022 Nov 4. [https://doi.org/10.1200/jco.21.02937 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839304/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36332179/ PubMed] | ||
+ | ==Vinorelbine & Trastuzumab (VH) {{#subobject:932de7|Regimen=1}}== | ||
+ | VH: '''<u>V</u>'''inorelbine & '''<u>H</u>'''erceptin (Trastuzumab) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, 2 out of 3 weeks {{#subobject:gh10hj|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7823434/ Rugo et al. 2021 (SOPHIA)] | ||
+ | |2015-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#Capecitabine_.26_Margetuximab|Capecitabine & Margetuximab]]<br>1b. [[#Eribulin_.26_Margetuximab|Eribulin & Margetuximab]]<br>1c. [[#Gemcitabine_.26_Margetuximab|Gemcitabine & Margetuximab]]<br>1d. [[#Vinorelbine_.26_Margetuximab|Vinorelbine & Margetuximab]] | ||
+ | | style="background-color:#fc8d59" |Seems to have inferior PFS | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ Yamamoto et al. 2022 (PRECIOUS)] | ||
+ | |2015-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#THP_.28Docetaxel.29_3|THP (Docetaxel)]]<br>1b. [[#THP_.28Paclitaxel.29|THP (Paclitaxel)]]<br>1c. [[#nab-Paclitaxel.2C_Pertuzumab.2C_Trastuzumab|nab-Paclitaxel, Pertuzumab, Trastuzumab]]<br>1d. [[#VHP|VHP]]<br>1e. [[#EHP|EHP]]<br>1f. [[#XHP|XHP]]<br>1g. [[#GHP|GHP]] | ||
+ | | style="background-color:#fee08b" |Might have inferior OS | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: this is the lower bound of vinorelbine dosing specified in SOPHIA.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *PRECIOUS: History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this. | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, 2 out of 3 weeks {{#subobject:gh30hj|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7823434/ Rugo et al. 2021 (SOPHIA)] | ||
+ | |2015-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#Capecitabine_.26_Margetuximab|Capecitabine & Margetuximab]]<br>1b. [[#Eribulin_.26_Margetuximab|Eribulin & Margetuximab]]<br>1c. [[#Gemcitabine_.26_Margetuximab|Gemcitabine & Margetuximab]]<br>1d. [[#Vinorelbine_.26_Margetuximab|Vinorelbine & Margetuximab]] | ||
+ | | style="background-color:#fc8d59" |Seems to have inferior PFS | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: this is the upper bound of vinorelbine dosing specified in SOPHIA.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #3, weekly {{#subobject:55cd14|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S1470-2045(14)70138-X André et al. 2014 (BOLERO-3)] | ||
+ | |2009-2012 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#Vinorelbine_.26_Trastuzumab_.28VH.29_.26_Everolimus|VH & Everolimus]] | ||
+ | |style="background-color:#d73027"|Inferior PFS | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S1470-2045(15)00540-9 Harbeck et al. 2016 (LUX-Breast 1)] | ||
+ | |2010-2013 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[Stub#Afatinib_.26_Vinorelbine|Afatinib & Vinorelbine]] | ||
+ | |style="background-color:#ffffbf"|Did not meet primary endpoint of PFS<br>Median PFS: 5.6 vs 5.5 mo<br>(HR 0.91, 95% CI 0.71-1.16) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 4 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 2 mg/kg IV once on day 1 | ||
+ | '''7-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''BOLERO-3:''' André F, O'Regan R, Ozguroglu M, Toi M, Xu B, Jerusalem G, Masuda N, Wilks S, Arena F, Isaacs C, Yap YS, Papai Z, Lang I, Armstrong A, Lerzo G, White M, Shen K, Litton J, Chen D, Zhang Y, Ali S, Taran T, Gianni L. Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2014 May;15(6):580-91. Epub 2014 Apr 14. [https://doi.org/10.1016/S1470-2045(14)70138-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24742739/ PubMed] [https://clinicaltrials.gov/study/NCT01007942 NCT01007942] | ||
+ | # '''LUX-Breast 1:''' Harbeck N, Huang CS, Hurvitz S, Yeh DC, Shao Z, Im SA, Jung KH, Shen K, Ro J, Jassem J, Zhang Q, Im YH, Wojtukiewicz M, Sun Q, Chen SC, Goeldner RG, Uttenreuther-Fischer M, Xu B, Piccart-Gebhart M; LUX-Breast 1 study group. Afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one previous trastuzumab treatment (LUX-Breast 1): an open-label, randomised, phase 3 trial. Lancet Oncol. 2016 Mar;17(3):357-66. Epub 2016 Jan 26. [https://doi.org/10.1016/S1470-2045(15)00540-9 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26822398/ PubMed] [https://clinicaltrials.gov/study/NCT01125566 NCT01125566] | ||
+ | # '''SOPHIA:''' Rugo HS, Im SA, Cardoso F, Cortés J, Curigliano G, Musolino A, Pegram MD, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Kaufman B, Yerushalmi R, Fasching PA, Nordstrom JL, Bonvini E, Koenig S, Edlich S, Hong S, Rock EP, Gradishar WJ; SOPHIA Study Group. Efficacy of Margetuximab vs Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Apr 1;7(4):573-584. [https://doi.org/10.1001/jamaoncol.2020.7932 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7823434/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33480963/ PubMed] [https://clinicaltrials.gov/study/NCT02492711 NCT02492711] | ||
+ | ##'''Update:''' Rugo HS, Im SA, Cardoso F, Cortes J, Curigliano G, Musolino A, Pegram MD, Bachelot T, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Schwartz GN, Pluard TJ, Ricci F, Gwin WR 3rd, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Gal-Yam EN, Yerushalmi R, Fasching PA, Kaufman PA, Ashley EJ, Perez-Olle R, Hong S, Rosales MK, Gradishar WJ; SOPHIA Study Group. Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial. J Clin Oncol. 2023 Jan 10;41(2):198-205. Epub 2022 Nov 4. [https://doi.org/10.1200/jco.21.02937 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839304/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36332179/ PubMed] | ||
+ | #'''PRECIOUS:''' Yamamoto Y, Iwata H, Taira N, Masuda N, Takahashi M, Yoshinami T, Ueno T, Toyama T, Yamanaka T, Takano T, Kashiwaba M, Tsugawa K, Hasegawa Y, Tamura K, Tada H, Hara F, Fujisawa T, Niikura N, Saji S, Morita S, Toi M, Ohno S. Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS). Cancer Sci. 2022 Sep;113(9):3169-3179. Epub 2022 Jul 23. [https://doi.org/10.1111/cas.15474 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ link to PMC article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/35754298/ PubMed] UMIN000018202 | ||
+ | # '''SWOG-S0347:''' [https://clinicaltrials.gov/study/NCT00103233 NCT00103233] | ||
+ | |||
+ | ==Vinorelbine & Trastuzumab (VH) & Everolimus {{#subobject:8hude7|Regimen=1}}== | ||
+ | VH & Everolimus: '''<u>V</u>'''inorelbine, '''<u>H</u>'''erceptin (Trastuzumab), Everolimus | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:5jha14|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S1470-2045(14)70138-X André et al. 2014 (BOLERO-3)] | ||
+ | |2009-2012 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |[[#Vinorelbine_.26_Trastuzumab_.28VH.29_3|VH]] | ||
+ | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 7 vs 5.8 mo<br>(HR 0.78, 95% CI 0.65-0.95) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 4 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 2 mg/kg IV once on day 1 | ||
+ | *[[Everolimus (Afinitor)]] 5 mg PO once per day on days 1 to 7 | ||
+ | '''7-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''BOLERO-3:''' André F, O'Regan R, Ozguroglu M, Toi M, Xu B, Jerusalem G, Masuda N, Wilks S, Arena F, Isaacs C, Yap YS, Papai Z, Lang I, Armstrong A, Lerzo G, White M, Shen K, Litton J, Chen D, Zhang Y, Ali S, Taran T, Gianni L. Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2014 May;15(6):580-91. Epub 2014 Apr 14. [https://doi.org/10.1016/S1470-2045(14)70138-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24742739/ PubMed] [https://clinicaltrials.gov/study/NCT01007942 NCT01007942] | ||
+ | ==VHP {{#subobject:u81hc9|Regimen=1}}== | ||
+ | VHP: '''<u>V</u>'''inorelbine, '''<u>H</u>'''erceptin (Trastuzumab), '''<u>P</u>'''ertuzumab | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:1uioqq|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ Yamamoto et al. 2022 (PRECIOUS)] | ||
+ | |2015-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |1a. [[#Docetaxel_.26_Trastuzumab_.28TH.29_4|TH (Docetaxel)]]<br>1b. [[#Paclitaxel_.26_Trastuzumab_.28TH.29_4|TH (Paclitaxel)]]<br>1c. [[#nab-Paclitaxel_.26_Trastuzumab_2|nab-Paclitaxel & Trastuzumab]]<br>1d. [[#Vinorelbine_.26_Trastuzumab_.28VH.29_2|VH]]<br>1e. [[#Eribulin_.26_Trastuzumab|EH]]<br>1f. [[#Capecitabine_.26_Trastuzumab_.28XH.29_2|XH]]<br>1g. [[#Gemcitabine_.26_Trastuzumab|GH]] | ||
+ | | style="background-color:#d9ef8b" |Might have superior OS<sup>1</sup> (secondary endpoint)<br>Median OS: 28.8 vs 23.4 mo<br>(HR 0.71, 95% CI NA-1.03)<br><br>Seems to have superior PFS (primary endpoint)<br>Median PFS: 5.3 vs 4.2 mo<br>(sHR 0.76, 95% CI NA-0.97) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Results are based on a one-sided statistical analysis.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *PRECIOUS: History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this. | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Pertuzumab (Perjeta)]] as follows: | ||
+ | **Cycle 1: 840 mg IV once on day 1 | ||
+ | **Cycle 2 onwards: 420 mg IV once on day 1 | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''PRECIOUS:''' Yamamoto Y, Iwata H, Taira N, Masuda N, Takahashi M, Yoshinami T, Ueno T, Toyama T, Yamanaka T, Takano T, Kashiwaba M, Tsugawa K, Hasegawa Y, Tamura K, Tada H, Hara F, Fujisawa T, Niikura N, Saji S, Morita S, Toi M, Ohno S. Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS). Cancer Sci. 2022 Sep;113(9):3169-3179. Epub 2022 Jul 23. [https://doi.org/10.1111/cas.15474 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ link to PMC article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/35754298/ PubMed] UMIN000018202 | ||
+ | ==XHP {{#subobject:fa074d|Regimen=1}}== | ||
+ | XHP: '''<u>X</u>'''eloda (Capecitabine), '''<u>H</u>'''erceptin (Trastuzumab), '''<u>P</u>'''ertuzumab | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:b7d240|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/JCO.2016.70.6267 Urruticoechea et al. 2017 (PHEREXA)] | ||
+ | |2010-2013 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |[[#Capecitabine_.26_Trastuzumab_.28XH.29_2|Capecitabine & Trastuzumab]] | ||
+ | |style="background-color:#d9ef8b"|Might have superior PFS (primary endpoint)<br>Median PFS: 11.1 vs 9 mo<br>(HR 0.82, 95% CI 0.65-1.02) | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ Yamamoto et al. 2022 (PRECIOUS)] | ||
+ | |2015-2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |1a. [[#Docetaxel_.26_Trastuzumab_.28TH.29_4|TH (Docetaxel)]]<br>1b. [[#Paclitaxel_.26_Trastuzumab_.28TH.29_4|TH (Paclitaxel)]]<br>1c. [[#nab-Paclitaxel_.26_Trastuzumab_2|nab-Paclitaxel & Trastuzumab]]<br>1d. [[#Vinorelbine_.26_Trastuzumab_.28VH.29_2|VH]]<br>1e. [[#Eribulin_.26_Trastuzumab|EH]]<br>1f. [[#Capecitabine_.26_Trastuzumab_.28XH.29_2|XH]]<br>1g. [[#Gemcitabine_.26_Trastuzumab|GH]] | ||
+ | | style="background-color:#d9ef8b" |Might have superior OS<sup>1</sup> (secondary endpoint)<br>Median OS: 28.8 vs 23.4 mo<br>(HR 0.71, 95% CI NA-1.03)<br><br>Seems to have superior PFS (primary endpoint)<br>Median PFS: 5.3 vs 4.2 mo<br>(sHR 0.76, 95% CI NA-0.97) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Results are based on a one-sided statistical analysis.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *PRECIOUS: History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this. | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Pertuzumab (Perjeta)]] as follows: | ||
+ | **Cycle 1: 840 mg IV once on day 1 | ||
+ | **Cycle 2 onwards: 420 mg IV once on day 1 | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''PHEREXA:''' Urruticoechea A, Rizwanullah M, Im SA, Ruiz ACS, Láng I, Tomasello G, Douthwaite H, Badovinac Crnjevic T, Heeson S, Eng-Wong J, Muñoz M. Randomized phase III trial of trastuzumab plus capecitabine with or without pertuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who experienced disease progression during or after trastuzumab-based therapy. J Clin Oncol. 2017 Sep 10;35(26):3030-3038. Epub 2017 Apr 24. [https://doi.org/10.1200/JCO.2016.70.6267 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28437161/ PubMed] [https://clinicaltrials.gov/study/NCT01026142 NCT01026142] | ||
+ | #'''PRECIOUS:''' Yamamoto Y, Iwata H, Taira N, Masuda N, Takahashi M, Yoshinami T, Ueno T, Toyama T, Yamanaka T, Takano T, Kashiwaba M, Tsugawa K, Hasegawa Y, Tamura K, Tada H, Hara F, Fujisawa T, Niikura N, Saji S, Morita S, Toi M, Ohno S. Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS). Cancer Sci. 2022 Sep;113(9):3169-3179. Epub 2022 Jul 23. [https://doi.org/10.1111/cas.15474 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9459345/ link to PMC article] '''dosing details in supplement have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/35754298/ PubMed] UMIN000018202 | ||
+ | |||
+ | =Maintenance for metastatic or unresectable disease= | ||
+ | ==Pertuzumab & Trastuzumab {{#subobject:75e894|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:ecd17f|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705202/ Baselga et al. 2011 (CLEOPATRA)] | ||
+ | |2008-2010 | ||
+ | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *First-line [[#THP_.28Docetaxel.29_3|THP (Docetaxel)]] for at least 6 cycles | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Pertuzumab (Perjeta)]] 420 mg IV once on day 1 | ||
+ | *[[Trastuzumab (Herceptin)]] 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''CLEOPATRA:''' Baselga J, Cortés J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, Clark E, Benyunes MC, Ross G, Swain SM; CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012 Jan 12;366(2):109-19. Epub 2011 Dec 7. [https://doi.org/10.1056/NEJMoa1113216 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705202/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22149875/ PubMed] [https://clinicaltrials.gov/study/NCT00567190 NCT00567190] | ||
+ | ## '''Update:''' Swain SM, Kim SB, Cortés J, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Knott A, Clark E, Ross G, Benyunes MC, Baselga J. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2013 May;14(6):461-71. Epub 2013 Apr 18. [https://doi.org/10.1016/S1470-2045(13)70130-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076842/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23602601/ PubMed] | ||
+ | ##'''HRQoL analysis:''' Cortés J, Baselga J, Im YH, Im SA, Pivot X, Ross G, Clark E, Knott A, Swain SM. Health-related quality-of-life assessment in CLEOPATRA, a phase III study combining pertuzumab with trastuzumab and docetaxel in metastatic breast cancer. Ann Oncol. 2013 Oct;24(10):2630-2635. Epub 2013 Jul 17. [https://doi.org/10.1093/annonc/mdt274 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23868905/ PubMed] | ||
+ | ## '''Update:''' Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S, Clark E, Ross G, Benyunes MC, Cortés J; CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015 Feb 19;372(8):724-34. [https://doi.org/10.1056/NEJMoa1413513 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5584549/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25693012/ PubMed] | ||
+ | ## '''Update:''' Swain SM, Miles D, Kim SB, Im YH, Im SA, Semiglazov V, Ciruelos E, Schneeweiss A, Loi S, Monturus E, Clark E, Knott A, Restuccia E, Benyunes MC, Cortés J; CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020 Apr;21(4):519-530. Epub 2020 Mar 12. [https://doi.org/10.1016/s1470-2045(19)30863-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32171426/ PubMed] | ||
+ | ==Trastuzumab monotherapy {{#subobject:c88145|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, q3wk dosing {{#subobject:da43ac|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.3816/CBC.2005.n.047 Perez et al. 2005 (NCCTG 983252)] | ||
+ | |1999-04 to 2003-07 | ||
+ | | style="background-color:#91cf61" |Phase 2 | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2010.28.6450 Valero et al. 2010 (BCIRG 007)] | ||
+ | |2001-2004 | ||
+ | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705202/ Baselga et al. 2011 (CLEOPATRA)] |
− | + | |2008-2010 | |
− | + | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT | |
− | |||
− | |||
− | |||
− | | | ||
− | |||
− | |||
− | |||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/JCO.2014.56.9590 Gelmon et al. 2015 (NCIC-CTG MA.31)] |
− | | | + | |2008-2011 |
− | + | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT | |
− | |style="background-color:# | ||
|- | |- | ||
|} | |} | ||
− | ==== | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | *[[ | + | ====Preceding treatment==== |
+ | *NCCTG 983252: First-line [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Trastuzumab|TPC (q3wk)]] x 8 | ||
+ | *BCIRG 007: First-line [[#Docetaxel_.26_Trastuzumab_.28TH.29_3|TH (Docetaxel)]] x 8 versus [[#TCH_.28Docetaxel.29_2|TCH (Taxotere)]] x 8 | ||
+ | *CLEOPATRA: First-line [[#Docetaxel_.26_Trastuzumab_.28TH.29_3|TH (Docetaxel)]] | ||
+ | *NCIC-CTG MA.31: First-line [[#Paclitaxel_.26_Trastuzumab_.28TH.29_3|TH (Paclitaxel)]] x 6 or [[#Docetaxel_.26_Trastuzumab_.28TH.29_3|TH (Docetaxel)]] x 8 | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
*[[Trastuzumab (Herceptin)]] 6 mg/kg IV once on day 1 | *[[Trastuzumab (Herceptin)]] 6 mg/kg IV once on day 1 | ||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div><br> | |
− | === | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | + | ===Regimen variant #2, weekly dosing {{#subobject:1ac92c|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" | |
− | + | !style="width: 33%"|Study | |
− | {| class="wikitable" style=" | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2005.04.1764 Robert et al. 2006] |
− | + | |1998-2002 | |
− | + | |style="background-color:#91cf61"|Non-randomized part of phase 3 RCT | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | | | ||
− | |||
− | |style="background-color:# | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.3816/CBC.2005.n.047 Perez et al. 2005 (NCCTG 983252)] |
− | | | + | |1999-04 to 2003-07 |
− | + | | style="background-color:#91cf61" |Phase 2 | |
− | |style="background-color:# | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2005.04.173 Marty et al. 2005 (M77001)] |
− | | | + | |2000-2002 |
− | + | |style="background-color:#91cf61"|Non-randomized part of phase 2 RCT | |
− | |style="background-color:# | ||
|- | |- | ||
|} | |} | ||
− | ==== | + | <div class="toccolours" style="background-color:#cbd5e8"> |
− | *[[ | + | ====Preceding treatment==== |
− | *[[Trastuzumab (Herceptin)]] | + | *M77001: First-line [[#Docetaxel_.26_Trastuzumab_.28TH.29_3|TH (Docetaxel)]] for at least 6 cycles |
− | + | *NCCTG 983252: First-line [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Trastuzumab|TPC (weekly)]] x 6 | |
− | ''' | + | *Robert et al. 2006: First-line [[#Paclitaxel_.26_Trastuzumab_.28TH.29_3|TP]] x 6 versus [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Trastuzumab|TPC]] x 6 |
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] 2 mg/kg IV once per day on days 1, 8, 15, 22 | ||
+ | '''28-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # | + | # '''M77001:''' Marty M, Cognetti F, Maraninchi D, Snyder R, Mauriac L, Tubiana-Hulin M, Chan S, Grimes D, Antón A, Lluch A, Kennedy J, O'Byrne K, Conte P, Green M, Ward C, Mayne K, Extra JM. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol. 2005 Jul 1;23(19):4265-74. Epub 2005 May 23. [https://doi.org/10.1200/jco.2005.04.173 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15911866/ PubMed] |
− | # | + | # '''NCCTG 983252:''' Perez EA, Suman VJ, Rowland KM, Ingle JN, Salim M, Loprinzi CL, Flynn PJ, Mailliard JA, Kardinal CG, Krook JE, Thrower AR, Visscher DW, Jenkins RB. Two concurrent phase II trials of paclitaxel/carboplatin/trastuzumab (weekly or every-3-week schedule) as first-line therapy in women with HER2-overexpressing metastatic breast cancer: NCCTG study 983252. Clin Breast Cancer. 2005 Dec;6(5):425-32. [https://doi.org/10.3816/CBC.2005.n.047 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16381626/ PubMed] |
− | # | + | # Robert N, Leyland-Jones B, Asmar L, Belt R, Ilegbodu D, Loesch D, Raju R, Valentine E, Sayre R, Cobleigh M, Albain K, McCullough C, Fuchs L, Slamon D. Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer. J Clin Oncol. 2006 Jun 20;24(18):2786-92. [https://doi.org/10.1200/jco.2005.04.1764 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16782917/ PubMed] |
+ | # '''BCIRG 007:''' Valero V, Forbes J, Pegram MD, Pienkowski T, Eiermann W, von Minckwitz G, Roche H, Martin M, Crown J, Mackey JR, Fumoleau P, Rolski J, Mrsic-Krmpotic Z, Jagiello-Gruszfeld A, Riva A, Buyse M, Taupin H, Sauter G, Press MF, Slamon DJ. Multicenter phase III randomized trial comparing docetaxel and trastuzumab with docetaxel, carboplatin, and trastuzumab as first-line chemotherapy for patients with HER2-gene-amplified metastatic breast cancer (BCIRG 007 study): two highly active therapeutic regimens. J Clin Oncol. 2011 Jan 10;29(2):149-56. Epub 2010 Nov 29. [https://doi.org/10.1200/jco.2010.28.6450 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21115860/ PubMed] [https://clinicaltrials.gov/study/NCT00047255 NCT00047255] | ||
+ | # '''CLEOPATRA:''' Baselga J, Cortés J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, Clark E, Benyunes MC, Ross G, Swain SM; CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012 Jan 12;366(2):109-19. Epub 2011 Dec 7. [https://doi.org/10.1056/NEJMoa1113216 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705202/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22149875/ PubMed] [https://clinicaltrials.gov/study/NCT00567190 NCT00567190] | ||
+ | ## '''Update:''' Swain SM, Kim SB, Cortés J, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Knott A, Clark E, Ross G, Benyunes MC, Baselga J. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2013 May;14(6):461-71. Epub 2013 Apr 18. [https://doi.org/10.1016/S1470-2045(13)70130-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076842/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23602601/ PubMed] | ||
+ | ##'''HRQoL analysis:''' Cortés J, Baselga J, Im YH, Im SA, Pivot X, Ross G, Clark E, Knott A, Swain SM. Health-related quality-of-life assessment in CLEOPATRA, a phase III study combining pertuzumab with trastuzumab and docetaxel in metastatic breast cancer. Ann Oncol. 2013 Oct;24(10):2630-2635. Epub 2013 Jul 17. [https://doi.org/10.1093/annonc/mdt274 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23868905/ PubMed] | ||
+ | ## '''Update:''' Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S, Clark E, Ross G, Benyunes MC, Cortés J; CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015 Feb 19;372(8):724-34. [https://doi.org/10.1056/NEJMoa1413513 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5584549/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25693012/ PubMed] | ||
+ | ## '''Update:''' Swain SM, Miles D, Kim SB, Im YH, Im SA, Semiglazov V, Ciruelos E, Schneeweiss A, Loi S, Monturus E, Clark E, Knott A, Restuccia E, Benyunes MC, Cortés J; CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020 Apr;21(4):519-530. Epub 2020 Mar 12. [https://doi.org/10.1016/s1470-2045(19)30863-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32171426/ PubMed] | ||
+ | # '''NCIC-CTG MA.31:''' Gelmon KA, Boyle FM, Kaufman B, Huntsman DG, Manikhas A, Di Leo A, Martin M, Schwartzberg LS, Lemieux J, Aparicio S, Shepherd LE, Dent S, Ellard SL, Tonkin K, Pritchard KI, Whelan TJ, Nomikos D, Nusch A, Coleman RE, Mukai H, Tjulandin S, Khasanov R, Rizel S, Connor AP, Santillana SL, Chapman JA, Parulekar WR. Lapatinib or trastuzumab plus taxane therapy for human epidermal growth factor receptor 2-positive advanced breast cancer: final results of NCIC-CTG MA.31. J Clin Oncol. 2015 May 10;33(14):1574-83. Epub 2015 Mar 16. [https://doi.org/10.1200/JCO.2014.56.9590 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25779558/ PubMed] [https://clinicaltrials.gov/study/NCT00667251 NCT00667251] | ||
=Additional resources= | =Additional resources= | ||
− | *[ | + | *[https://www.cancer.gov/bcrisktool/ Gail model Breast Cancer Risk Assessment Tool] |
**[[Gail model breast cancer risk factors]] | **[[Gail model breast cancer risk factors]] | ||
− | *[[Breast cancer BRCA1 | + | *[[Breast cancer BRCA1 & BRCA2 genetic testing]] |
− | *[ | + | *[https://www.mycancergenome.org/content/disease/breast-carcinoma/ My Cancer Genome] |
− | + | [[Category:Breast cancer regimens]] | |
− | + | [[Category:Biomarker-specific pages]] | |
− | + | [[Category:Malignant breast neoplasm]] | |
− | |||
− | |||
− | [[Category:Breast cancer | ||
− | [[Category: | ||
− | [[Category: |
Latest revision as of 12:09, 20 July 2024
Section editor | |
---|---|
Gayathri Nagaraj, MD Loma Linda University Loma Linda, CA, USA |
Are you looking for a regimen, but can't find it here? It is possible that we've moved it to the historical regimens page. For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!
Note: these are regimens tested in biomarker-specific populations, please see the main breast cancer page for other regimens.
- Regimens for ER/HER2 co-expressing ("double positive") breast cancer are here.
- Regimens for CNS metastases are here.
123 regimens on this page
203 variants on this page
|
Guidelines
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
ASCO
- 2022: Ramakrishna et al. Management of Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases PubMed
- 2018: Ramakrishna et al. Recommendations on disease management for patients with advanced human epidermal growth factor receptor 2-positive breast cancer and brain metastases: American Society of Clinical Oncology clinical practice guideline update PubMed
- 2014: Ramakrishna et al. Recommendations on disease management for patients with advanced human epidermal growth factor receptor 2-positive breast cancer and brain metastases: American Society of Clinical Oncology clinical practice guideline link to PMC article PubMed
- 2022: Giordano et al. Systemic Therapy for Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer PubMed
- 2018: Giordano et al. Systemic therapy for patients with advanced human epidermal growth factor receptor 2–positive breast cancer: ASCO Clinical Practice Guideline update PubMed
- 2014: Giordano et al. Systemic therapy for patients with advanced human epidermal growth factor receptor 2-positive breast cancer: American Society of Clinical Oncology clinical practice guideline link to PMC article PubMed
- 2021: Korde et al. Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer: ASCO Guideline link to PMC article PubMed
- 2020: Denduluri et al. Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer: ASCO Guideline Update PubMed
- 2018: Denduluri et al. Selection of optimal adjuvant chemotherapy and targeted therapy for early breast cancer: ASCO clinical practice guideline focused update PubMed
- 2016: Harris et al. Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: American Society of Clinical Oncology Clinical Practice Guideline PubMed
- 2015: Van Poznak et al. Use of biomarkers to guide decisions on systemic therapy for women with metastatic breast cancer: American Society of Clinical Oncology Clinical Practice Guideline PubMed
ASCO/CAP
- 2023: Wolff et al. Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: ASCO–College of American Pathologists Guideline Update PubMed
- 2014: Wolff et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update PubMed
- 2013: Wolff et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update PubMed
- 2007: Wolff et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer PubMed
ESMO
- 2023: Tarantino et al. ESMO expert consensus statements (ECS) on the definition, diagnosis, and management of HER2-low breast cancer PubMed
- 2017: Cardoso et al. 3rd ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3). PubMed
- 2015: Senkus et al. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. PubMed
NCCN
- NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Breast Cancer.
St Gallen Breast Guidelines
- 2019: Burstein et al. Estimating the benefits of therapy for early-stage breast cancer: the St. Gallen International Consensus Guidelines for the primary therapy of early breast cancer 2019 PubMed
- 2017: Curigliano et al. St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2017 link to PMC article PubMed
- 2015: Coates et al. Tailoring therapies—improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015 link to PMC article PubMed
Neoadjuvant therapy, sequential regimens
AC-TH (Paclitaxel)
AC-TH: Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxol (Paclitaxel) & Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Robidoux et al. 2013 (NSABP B-41) | 2007-2011 | Phase 3 (C) | 1. AC-THL | Might have inferior pCR rate |
2. AC-TL | Did not meet primary endpoint of pCR rate |
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, TH portion (cycles 5 to 8)
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22
- Cycles 6 to 8: 2 mg/kg IV once per day on days 1, 8, 15, 22
21-day cycle for 4 cycles, then 28-day cycle for 4 cycles (AC x 4; TH x 4)
Subsequent treatment
- Surgery, then adjuvant trastuzumab for a total of 52 weeks of therapy.
References
- NSABP B-41: Robidoux A, Tang G, Rastogi P, Geyer CE Jr, Azar CA, Atkins JN, Fehrenbacher L, Bear HD, Baez-Diaz L, Sarwar S, Margolese RG, Farrar WB, Brufsky AM, Shibata HR, Bandos H, Paik S, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1183-92. Epub 2013 Oct 4. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00486668
AC-THL (Paclitaxel)
AC-THL: Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxol (Paclitaxel), Herceptin (Trastuzumab), Lapatinib
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Robidoux et al. 2013 (NSABP B-41) | 2007-2011 | Phase 3 (E-esc) | 1. AC-TH | Might have superior pCR rate (primary endpoint) |
2. AC-TL | Might have superior pCR rate (primary endpoint) |
Note: This lapatinib dosing was based on a mid-protocol amendment due to excess diarrhea reported in other trials.
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Chemotherapy, THL portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, THL portion (cycles 5 to 8)
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22
- Cycles 6 to 8: 2 mg/kg IV once per day on days 1, 8, 15, 22
- Lapatinib (Tykerb) as follows:
- Cycles 5 to 8: 750 mg PO once per day
21-day cycle for 4 cycles, then 28-day cycle for 4 cycles (AC x 4; THL x 4)
Subsequent treatment
- Surgery, then adjuvant trastuzumab for a total of 52 weeks of therapy
References
- NSABP B-41: Robidoux A, Tang G, Rastogi P, Geyer CE Jr, Azar CA, Atkins JN, Fehrenbacher L, Bear HD, Baez-Diaz L, Sarwar S, Margolese RG, Farrar WB, Brufsky AM, Shibata HR, Bandos H, Paik S, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1183-92. Epub 2013 Oct 4. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00486668
AC-THP (Docetaxel)
AC-THP: Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxotere (Docetaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tan et al. 2021 (FeDeriCa) | 2018-06-14 to 2018-12-24 | Phase 3 (C) | 1a. ddAC-THP (Paclitaxel, Phesgo) 1b. AC-THP (Docetaxel, Phesgo) |
Non-inferior serum trough |
Note: Docetaxel dose was esclated in cycles 6 to 8 if tolerated.
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Chemotherapy, THP portion (cycles 5 to 8)
- Docetaxel (Taxotere) as follows:
- Cycle 5: 75 mg/m2 IV once on day 1
- Cycles 6 to 8: 100 mg/m2 IV once on day 1
Targeted therapy, THP portion (cycles 5 to 8)
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 8: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 8: 420 mg IV once on day 1
21-day cycle for 8 cycles (AC x 4; THP x 4)
References
- FeDeriCa: Tan AR, Im SA, Mattar A, Colomer R, Stroyakovskii D, Nowecki Z, De Laurentiis M, Pierga JY, Jung KH, Schem C, Hogea A, Badovinac Crnjevic T, Heeson S, Shivhare M, Kirschbrown WP, Restuccia E, Jackisch C; FeDeriCa study group. Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection plus chemotherapy in HER2-positive early breast cancer (FeDeriCa): a randomised, open-label, multicentre, non-inferiority, phase 3 study. Lancet Oncol. 2021 Jan;22(1):85-97. Epub 2020 Dec 21. Erratum in: Lancet Oncol. 2021 Feb;22(2):e42. link to original article dosing details in supplement have been reviewed by our editors PubMed NCT03493854
AC-THP (Docetaxel, Phesgo)
AC-THP (Phesgo): Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxotere (Docetaxel) and Phesgo
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tan et al. 2021 (FeDeriCa) | 2018-06-14 to 2018-12-24 | Phase 3 (E-RT-switch-ic) | 1a. ddAC-THP 1b. AC-THP |
Non-inferior serum trough (primary endpoint) |
Note: Docetaxel dose was esclated in cycles 6 to 8 if tolerated.
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Chemotherapy, THP (Phesgo) portion (cycles 5 to 8)
- Docetaxel (Taxotere) as follows:
- Cycle 5: 75 mg/m2 IV once on day 1
- Cycles 6 to 8: 100 mg/m2 IV once on day 1
Targeted therapy, THP (Phesgo) portion (cycles 5 to 8)
- Pertuzumab and Trastuzumab hyaluronidase (Phesgo) as follows:
- Cycle 5: 1200/600 SC once on day 1
- Cycles 6 to 8: 600/600 SC once on day 1
21-day cycle for 8 cycles (AC x 4; THP (Phesgo) x 4)
References
- FeDeriCa: Tan AR, Im SA, Mattar A, Colomer R, Stroyakovskii D, Nowecki Z, De Laurentiis M, Pierga JY, Jung KH, Schem C, Hogea A, Badovinac Crnjevic T, Heeson S, Shivhare M, Kirschbrown WP, Restuccia E, Jackisch C; FeDeriCa study group. Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection plus chemotherapy in HER2-positive early breast cancer (FeDeriCa): a randomised, open-label, multicentre, non-inferiority, phase 3 study. Lancet Oncol. 2021 Jan;22(1):85-97. Epub 2020 Dec 21. Erratum in: Lancet Oncol. 2021 Feb;22(2):e42. link to original article dosing details in supplement have been reviewed by our editors PubMed NCT03493854
ddAC-THP (Paclitaxel)
ddAC-THP: dose-dense Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxol (Paclitaxel), Herceptin (Trastuzumab), Pertuzumab
ddAC-PacPH: dose-dense Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Paclitaxel, Pertuzumab, Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Swain et al. 2018 (BERENICE) | 2014-2015 | Phase 2 (RT) | ||
Tan et al. 2021 (FeDeriCa) | 2018-06-14 to 2018-12-24 | Phase 3 (C) | 1a. ddAC-THP (Paclitaxel, Phesgo) 1b. AC-THP (Docetaxel, Phesgo) |
Non-inferior serum trough |
Huober et al. 2022 (IMpassion050) | 2019-01 to 2020-08 | Phase 3 (C) | ddAC-THP & Atezolizumab | Did not meet primary endpoint of pCR rate |
Chemotherapy, ddAC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Supportive therapy, ddAC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, THP portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, THP portion (cycles 5 to 8)
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 8: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 8: 420 mg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 4 cycles (ddAC x 4; THP x 4)
References
- BERENICE: Swain SM, Ewer MS, Viale G, Delaloge S, Ferrero JM, Verrill M, Colomer R, Vieira C, Werner TL, Douthwaite H, Bradley D, Waldron-Lynch M, Kiermaier A, Eng-Wong J, Dang C; BERENICE Study Group. Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): a phase II, open-label, multicenter, multinational cardiac safety study. Ann Oncol. 2018 Mar 1;29(3):646-653. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT02132949
- Update: Dang C, Ewer MS, Delaloge S, Ferrero JM, Colomer R, de la Cruz-Merino L, Werner TL, Dadswell K, Verrill M, Eiger D, Sarkar S, de Haas SL, Restuccia E, Swain SM. BERENICE Final Analysis: Cardiac Safety Study of Neoadjuvant Pertuzumab, Trastuzumab, and Chemotherapy Followed by Adjuvant Pertuzumab and Trastuzumab in HER2-Positive Early Breast Cancer. Cancers (Basel). 2022 May 24;14(11):2596. link to original article link to PMC article PubMed
- FeDeriCa: Tan AR, Im SA, Mattar A, Colomer R, Stroyakovskii D, Nowecki Z, De Laurentiis M, Pierga JY, Jung KH, Schem C, Hogea A, Badovinac Crnjevic T, Heeson S, Shivhare M, Kirschbrown WP, Restuccia E, Jackisch C; FeDeriCa study group. Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection plus chemotherapy in HER2-positive early breast cancer (FeDeriCa): a randomised, open-label, multicentre, non-inferiority, phase 3 study. Lancet Oncol. 2021 Jan;22(1):85-97. Epub 2020 Dec 21. Erratum in: Lancet Oncol. 2021 Feb;22(2):e42. link to original article dosing details in supplement have been reviewed by our editors PubMed NCT03493854
- IMpassion050: Huober J, Barrios CH, Niikura N, Jarząb M, Chang YC, Huggins-Puhalla SL, Pedrini J, Zhukova L, Graupner V, Eiger D, Henschel V, Gochitashvili N, Lambertini C, Restuccia E, Zhang H; IMpassion050 Trial Investigators. Atezolizumab With Neoadjuvant Anti-Human Epidermal Growth Factor Receptor 2 Therapy and Chemotherapy in Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: Primary Results of the Randomized Phase III IMpassion050 Trial. J Clin Oncol. 2022 Sep 1;40(25):2946-2956. Epub 2022 Jun 28. link to original article link to PMC article PubMed NCT03726879
ddAC-THP (Paclitaxel, Phesgo)
ddAC-THP (Phesgo): dose-dense Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxol (Paclitaxel) and Phesgo
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tan et al. 2021 (FeDeriCa) | 2018-06-14 to 2018-12-24 | Phase 3 (E-RT-switch-ic) | 1a. ddAC-THP 1b. AC-THP |
Non-inferior serum trough (primary endpoint) |
Chemotherapy, ddAC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Supportive therapy, ddAC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, THP (Phesgo) portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, THP (Phesgo) portion (cycles 5 to 8)
- Pertuzumab and Trastuzumab hyaluronidase (Phesgo) as follows:
- Cycle 5: 1200/600 SC once on day 1
- Cycles 6 to 8: 600/600 SC once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 4 cycles (ddAC x 4; THP (Phesgo) x 4)
References
- FeDeriCa: Tan AR, Im SA, Mattar A, Colomer R, Stroyakovskii D, Nowecki Z, De Laurentiis M, Pierga JY, Jung KH, Schem C, Hogea A, Badovinac Crnjevic T, Heeson S, Shivhare M, Kirschbrown WP, Restuccia E, Jackisch C; FeDeriCa study group. Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection plus chemotherapy in HER2-positive early breast cancer (FeDeriCa): a randomised, open-label, multicentre, non-inferiority, phase 3 study. Lancet Oncol. 2021 Jan;22(1):85-97. Epub 2020 Dec 21. Erratum in: Lancet Oncol. 2021 Feb;22(2):e42. link to original article dosing details in supplement have been reviewed by our editors PubMed NCT03493854
AC-TL (Paclitaxel)
AC-TL: Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxol (Paclitaxel) & Lapatinib
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Robidoux et al. 2013 (NSABP B-41) | 2007-2011 | Phase 3 (E-switch-ic) | 1. AC-TH | Did not meet primary endpoint of pCR rate |
2. AC-THL | Might have inferior pCR rate (primary endpoint) |
Note: This lapatinib dosing was based on a mid-protocol amendment due to excess diarrhea reported in other trials.
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Chemotherapy, TL portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, TL portion (cycles 5 to 8)
- Lapatinib (Tykerb) 1250 mg PO once per day on days 1 to 28
21-day cycle for 4 cycles, then 28-day cycle for 4 cycles (AC x 4; TL x 4)
Subsequent treatment
- Surgery, then adjuvant trastuzumab for a total of 52 weeks of therapy
References
- NSABP B-41: Robidoux A, Tang G, Rastogi P, Geyer CE Jr, Azar CA, Atkins JN, Fehrenbacher L, Bear HD, Baez-Diaz L, Sarwar S, Margolese RG, Farrar WB, Brufsky AM, Shibata HR, Bandos H, Paik S, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1183-92. Epub 2013 Oct 4. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00486668
EC-TH (Docetaxel)
EC-TH: Epirubicin & Cyclophosphamide, followed by Taxotere (Docetaxel) & Herceptin (Trastuzumab)
EC-DT: Epirubicin & Cyclophosphamide, followed by Docetaxel & Trastuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Alba et al. 2014 (GEICAM 2006-14) | 2009-02 to 2010-10 | Phase 3 (C) | EC-TL | Superior pCR rate (primary endpoint) |
Chemotherapy, EC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 5 to 8)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, TH portion (cycles 5 to 8)
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 8: 6 mg/kg IV once on day 1
21-day cycle for 8 cycles (EC x 4; TH x 4)
Subsequent treatment
References
- GEICAM 2006-14: Alba E, Albanell J, de la Haba J, Barnadas A, Calvo L, Sánchez-Rovira P, Ramos M, Rojo F, Burgués O, Carrasco E, Caballero R, Porras I, Tibau A, Cámara MC, Lluch A. Trastuzumab or lapatinib with standard chemotherapy for HER2-positive breast cancer: results from the GEICAM/2006-14 trial. Br J Cancer. 2014 Mar 4;110(5):1139-47. Epub 2014 Jan 23. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00841828
ECH-TH (Docetaxel)
ECH-TH: Epirubicin, Cyclophosphamide, Herceptin (Trastuzumab), followed by Taxotere (Docetaxel) & Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Untch et al. 2012 (GeparQuintoHER2) | 2007-2010 | Phase 3 (C) | ECL-TL | Seems to have superior pCR rate (primary endpoint) |
Chemotherapy, ECH portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Targeted therapy, ECH portion (cycles 1 to 4)
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 4: 6 mg/kg IV once on day 1
Chemotherapy, TH portion (cycles 5 to 8)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, TH portion (cycles 5 to 8)
- Trastuzumab (Herceptin) 6 mg/kg IV once on day 1
21-day cycle for 8 cycles (ECH x 4; TH x 4)
Subsequent treatment
- Surgery, then adjuvant trastuzumab for 1 year total
References
- GeparQuintoHER2: Untch M, Loibl S, Bischoff J, Eidtmann H, Kaufmann M, Blohmer JU, Hilfrich J, Strumberg D, Fasching PA, Kreienberg R, Tesch H, Hanusch C, Gerber B, Rezai M, Jackisch C, Huober J, Kühn T, Nekljudova V, von Minckwitz G; German Breast Group; Arbeitsgemeinschaft Gynäkologische Onkologie-Breast Study Group. Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial. Lancet Oncol. 2012 Feb;13(2):135-44. Epub 2012 Jan 17. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00567554
- Update: Untch M, von Minckwitz G, Gerber B, Schem C, Rezai M, Fasching PA, Tesch H, Eggemann H, Hanusch C, Huober J, Solbach C, Jackisch C, Kunz G, Blohmer JU, Hauschild M, Fehm T, Nekljudova V, Loibl S; GBG; AGO-B Study Group. Survival analysis after neoadjuvant chemotherapy with trastuzumab or lapatinib in patients with human epidermal growth factor receptor 2-positive breast cancer in the GeparQuinto (G5) study (GBG 44). J Clin Oncol. 2018 May 1;36(13):1308-1316. Epub 2018 Mar 15. link to original article PubMed
FEC-TH (Paclitaxel)
FEC-TH: Fluorouracil, Epirubicin, Cyclophosphamide, followed by Taxol (Paclitaxel) & Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Buzdar et al. 2013 (ACOSOG Z1041) | 2007-2011 | Phase 3 (C) | TH-FEC & H | Did not meet primary endpoint of pCR |
Chemotherapy, FEC portion (cycles 1 to 4)
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 6 to 8: 2 mg/kg IV once per day on days 1, 8, 15
'21-day cycle for 8 cycles (FEC x 4; TH x 4)
Subsequent treatment
References
- ACOSOG Z1041: Buzdar AU, Suman VJ, Meric-Bernstam F, Leitch AM, Ellis MJ, Boughey JC, Unzeitig G, Royce M, McCall LM, Ewer MS, Hunt KK; American College of Surgeons Oncology Group. Fluorouracil, epirubicin, and cyclophosphamide (FEC-75) followed by paclitaxel plus trastuzumab versus paclitaxel plus trastuzumab followed by FEC-75 plus trastuzumab as neoadjuvant treatment for patients with HER2-positive breast cancer (Z1041): a randomised, controlled, phase 3 trial. Lancet Oncol. 2013 Dec;14(13):1317-25. Epub 2013 Nov 13. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00513292
- Update: Buzdar AU, Suman VJ, Meric-Bernstam F, Leitch AM, Ellis MJ, Boughey JC, Unzeitig GW, Royce ME, Hunt KK. Disease-Free and Overall Survival Among Patients With Operable HER2-Positive Breast Cancer Treated With Sequential vs Concurrent Chemotherapy: The ACOSOG Z1041 (Alliance) Randomized Clinical Trial. JAMA Oncol. 2019 Jan 1;5(1):45-50. link to original article link to PMC article PubMed
FEC-THP (Docetaxel)
FEC-THP: Fluorouracil, Epirubicin, Cyclophosphamide, followed by Taxotere (Docetaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen variant #1, 3 x 3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Schneeweiss et al. 2013 (TRYPHAENA) | 2009-2011 | Randomized Phase 2 (E-RT-switch-ic) | 1. FEC & HP-THP 2. TCHP |
Not reported | Similar rates of LVSD (co-primary endpoint) |
Chemotherapy, FEC portion (cycles 1 to 3)
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Chemotherapy, THP portion (cycles 4 to 6)
- Docetaxel (Taxotere) as follows:
- Cycle 4: 75 mg/m2 IV once on day 1
- Cycles 5 & 6; if no toxic effects occurred: 100 mg/m2 IV once on day 1
Targeted therapy, THP portion (cycles 4 to 6)
- Trastuzumab (Herceptin) as follows:
- Cycle 4: 8 mg/kg IV once on day 1
- Cycles 5 & 6: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 4: 840 mg IV once on day 1
- Cycles 5 & 6: 420 mg IV once on day 1
21-day cycle for 6 cycles (FEC x 3; THP x 3)
Subsequent treatment
- Surgery, then further adjuvant treatment (radiotherapy, chemotherapy, hormonal treatment) according to local guidelines (a total of 1 year of trastuzumab was given)
Regimen variant #2, 4 x 4
Study | Dates of enrollment | Evidence |
---|---|---|
Swain et al. 2018 (BERENICE) | 2014-2015 | Phase 2 (RT) |
Chemotherapy, FEC portion (cycles 1 to 4)
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Chemotherapy, THP portion (cycles 5 to 8)
- Docetaxel (Taxotere) as follows:
- Cycle 5: 75 mg/m2 IV once on day 1
- Cycles 6 to 8; if no toxic effects occurred: 100 mg/m2 IV once on day 1
Targeted therapy, THP portion (cycles 5 to 8)
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 8: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 8: 420 mg IV once on day 1
21-day cycle for 8 cycles (FEC x 4; THP x 4)
References
- TRYPHAENA: Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, Tausch C, Seo JH, Tsai YF, Ratnayake J, McNally V, Ross G, Cortés J. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013 Sep;24(9):2278-84. Epub 2013 May 22. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00976989
- Update: Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Waldron-Lynch M, Eng-Wong J, Kirk S, Cortés J. Long-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: Evaluating pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer. Eur J Cancer. 2018 Jan;89:27-35. Epub 2017 Dec 8. link to original article PubMed
- BERENICE: Swain SM, Ewer MS, Viale G, Delaloge S, Ferrero JM, Verrill M, Colomer R, Vieira C, Werner TL, Douthwaite H, Bradley D, Waldron-Lynch M, Kiermaier A, Eng-Wong J, Dang C; BERENICE Study Group. Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): a phase II, open-label, multicenter, multinational cardiac safety study. Ann Oncol. 2018 Mar 1;29(3):646-653. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT02132949
- Update: Dang C, Ewer MS, Delaloge S, Ferrero JM, Colomer R, de la Cruz-Merino L, Werner TL, Dadswell K, Verrill M, Eiger D, Sarkar S, de Haas SL, Restuccia E, Swain SM. BERENICE Final Analysis: Cardiac Safety Study of Neoadjuvant Pertuzumab, Trastuzumab, and Chemotherapy Followed by Adjuvant Pertuzumab and Trastuzumab in HER2-Positive Early Breast Cancer. Cancers (Basel). 2022 May 24;14(11):2596. link to original article link to PMC article PubMed
Neratinib & Paclitaxel, then AC
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Park et al. 2016 (I-SPY 2 neratinib) | 2010-2013 | Adaptively Randomized Phase 2 (E-switch-ic) | 1a. TH-AC 1b. TH-ddAC |
Seems to have superior pCR rate (primary endpoint) |
Targeted therapy, neratinib & paclitaxel portion (cycles 1 to 4)
- Neratinib (Nerlynx) 240 mg PO once per day
Chemotherapy, neratinib & paclitaxel portion (cycles 1 to 4)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Supportive therapy, neratinib & paclitaxel portion (cycles 1 to 4)
- Loperamide (Imodium) 4 mg PO once on day 1, then 2 mg PO once 8 hours later, then 2 mg PO twice per day for two weeks, then decreased per patient choice, started on day 1 of neratinib
Chemotherapy, AC portion (cycles 5 to 8)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 8 cycles (neratinib & paclitaxel x 4; AC x 4)
Subsequent treatment
References
- I-SPY 2 neratinib: Park JW, Liu MC, Yee D, Yau C, van 't Veer LJ, Symmans WF, Paoloni M, Perlmutter J, Hylton NM, Hogarth M, DeMichele A, Buxton MB, Chien AJ, Wallace AM, Boughey JC, Haddad TC, Chui SY, Kemmer KA, Kaplan HG, Isaacs C, Nanda R, Tripathy D, Albain KS, Edmiston KK, Elias AD, Northfelt DW, Pusztai L, Moulder SL, Lang JE, Viscusi RK, Euhus DM, Haley BB, Khan QJ, Wood WC, Melisko M, Schwab R, Helsten T, Lyandres J, Davis SE, Hirst GL, Sanil A, Esserman LJ, Berry DA; I-SPY 2 Investigators. Adaptive randomization of neratinib in early breast cancer. N Engl J Med. 2016 Jul 7;375(1):11-22. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01042379
Neratinib & Paclitaxel, then ddAC
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Park et al. 2016 (I-SPY 2 neratinib) | 2010-2013 | Adaptively Randomized Phase 2 (E-switch-ic) | 1a. TH-AC 1b. TH-ddAC |
Seems to have superior pCR rate (primary endpoint) |
Targeted therapy, neratinib & paclitaxel portion (cycles 1 to 4)
- Neratinib (Nerlynx) 240 mg PO once per day
Chemotherapy, neratinib & paclitaxel portion (cycles 1 to 4)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Supportive therapy, neratinib & paclitaxel portion (cycles 1 to 4)
- Loperamide (Imodium) 4 mg PO once on day 1, then 2 mg PO once 8 hours later, then 2 mg PO twice per day for two weeks, then decreased per patient choice, started on day 1 of neratinib
Chemotherapy, ddAC portion (cycles 5 to 8)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Supportive therapy, ddAC portion (cycles 5 to 8)
- Pegfilgrastim (Neulasta) 6 mg SC once on day 2, given 24 hours after chemotherapy
21-day cycle for 4 cycles, then 14-day cycle for 4 cycles (neratinib & paclitaxel x 4; ddAC x 4)
Subsequent treatment
References
- I-SPY 2 neratinib: Park JW, Liu MC, Yee D, Yau C, van 't Veer LJ, Symmans WF, Paoloni M, Perlmutter J, Hylton NM, Hogarth M, DeMichele A, Buxton MB, Chien AJ, Wallace AM, Boughey JC, Haddad TC, Chui SY, Kemmer KA, Kaplan HG, Isaacs C, Nanda R, Tripathy D, Albain KS, Edmiston KK, Elias AD, Northfelt DW, Pusztai L, Moulder SL, Lang JE, Viscusi RK, Euhus DM, Haley BB, Khan QJ, Wood WC, Melisko M, Schwab R, Helsten T, Lyandres J, Davis SE, Hirst GL, Sanil A, Esserman LJ, Berry DA; I-SPY 2 Investigators. Adaptive randomization of neratinib in early breast cancer. N Engl J Med. 2016 Jul 7;375(1):11-22. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01042379
TH-AC (Paclitaxel)
TH-AC: Taxol (Paclitaxel) & Herceptin (Trastuzumab), followed by Adriamycin (Doxorubicin) & Cyclophosphamide
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Park et al. 2016 (I-SPY 2 neratinib) | 2010-2013 | Adaptively Randomized Phase 2 (C) | 1a. Neratinib & Paclitaxel, then AC 1b. Neratinib & Paclitaxel, then ddAC |
Seems to have inferior pCR rate |
Chemotherapy, TH portion (cycles 1 to 4)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 2 to 4: 2 mg/kg IV once per day on days 1, 8, 15
Chemotherapy, AC portion (cycles 5 to 8)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 8 cycles (TH x 4; AC x 4)
Subsequent treatment
References
- I-SPY 2 neratinib: Park JW, Liu MC, Yee D, Yau C, van 't Veer LJ, Symmans WF, Paoloni M, Perlmutter J, Hylton NM, Hogarth M, DeMichele A, Buxton MB, Chien AJ, Wallace AM, Boughey JC, Haddad TC, Chui SY, Kemmer KA, Kaplan HG, Isaacs C, Nanda R, Tripathy D, Albain KS, Edmiston KK, Elias AD, Northfelt DW, Pusztai L, Moulder SL, Lang JE, Viscusi RK, Euhus DM, Haley BB, Khan QJ, Wood WC, Melisko M, Schwab R, Helsten T, Lyandres J, Davis SE, Hirst GL, Sanil A, Esserman LJ, Berry DA; I-SPY 2 Investigators. Adaptive randomization of neratinib in early breast cancer. N Engl J Med. 2016 Jul 7;375(1):11-22. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01042379
TH-ddAC (Paclitaxel)
TH-ddAC: Taxol (Paclitaxel) & Herceptin (Trastuzumab), followed by dose-dense Adriamycin (Doxorubicin) & Cyclophosphamide
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Park et al. 2016 (I-SPY 2 neratinib) | 2010-2013 | Adaptively Randomized Phase 2 (C) | 1a. Neratinib & Paclitaxel, then AC 1b. Neratinib & Paclitaxel, then ddAC |
Seems to have inferior pCR rate |
Chemotherapy, TH portion (cycles 1 to 4)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 2 to 4: 2 mg/kg IV once per day on days 1, 8, 15
Chemotherapy, ddAC portion (cycles 5 to 8)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Supportive therapy, ddAC portion (cycles 5 to 8)
- Pegfilgrastim (Neulasta) 6 mg SC once on day 2, given 24 hours after chemotherapy
21-day cycle for 4 cycles, then 14-day cycle for 4 cycles (TH x 4; ddAC x 4)
Subsequent treatment
References
- I-SPY 2 neratinib: Park JW, Liu MC, Yee D, Yau C, van 't Veer LJ, Symmans WF, Paoloni M, Perlmutter J, Hylton NM, Hogarth M, DeMichele A, Buxton MB, Chien AJ, Wallace AM, Boughey JC, Haddad TC, Chui SY, Kemmer KA, Kaplan HG, Isaacs C, Nanda R, Tripathy D, Albain KS, Edmiston KK, Elias AD, Northfelt DW, Pusztai L, Moulder SL, Lang JE, Viscusi RK, Euhus DM, Haley BB, Khan QJ, Wood WC, Melisko M, Schwab R, Helsten T, Lyandres J, Davis SE, Hirst GL, Sanil A, Esserman LJ, Berry DA; I-SPY 2 Investigators. Adaptive randomization of neratinib in early breast cancer. N Engl J Med. 2016 Jul 7;375(1):11-22. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01042379
TH-FEC & H (Docetaxel)
TH-FEC & H: Taxotere (Docetaxel) & Herceptin (Trastuzumab), followed by Fluorouracil, Epirubicin, Cyclophosphamide, Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ismael et al. 2012 (HannaH) | 2009-10-19 to 2010-12-01 | Phase 3 (C) | TH-FEC & H (SC) | Non-inferior pCR rate |
Pivot et al. 2018 (SB3-G31-BC) | 2014-04 to 2015-08 | Phase 3 (C) | TH-FEC & H (trastuzumab-dttb) | Equivalent bpCR rate (primary endpoint) bpCR rate: 42% vs 51.7% |
Stebbing et al. 2017 (CT-P6 3.2) | 2014-08-07 to 2016-05-06 | Phase 3 (C) | TH-FEC & H (trastuzumab-pkrb) | Equivalent pCR rate (primary endpoint) pCR rate: 50.4% vs 46.8% |
Chemotherapy, T portion (cycles 1 to 4)
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Chemotherapy, FEC portion (cycles 5 to 8)
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
Targeted therapy, both portions
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 8: 6 mg/kg IV once on day 1
21-day cycle for 8 cycles (TH x 4; FEC & H x 4)
Subsequent treatment
- HannaH: Surgery
- SB3-G31-BC: Surgery, then adjuvant trastuzumab x 30 wk
References
- HannaH: Ismael G, Hegg R, Muehlbauer S, Heinzmann D, Lum B, Kim SB, Pienkowski T, Lichinitser M, Semiglazov V, Melichar B, Jackisch C. Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I-III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial. Lancet Oncol. 2012 Sep;13(9):869-78. Epub 2012 Aug 9. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00950300
- Update: Jackisch C, Kim SB, Semiglazov V, Melichar B, Pivot X, Hillenbach C, Stroyakovskiy D, Lum BL, Elliott R, Weber HA, Ismael G. Subcutaneous versus intravenous formulation of trastuzumab for HER2-positive early breast cancer: updated results from the phase III HannaH study. Ann Oncol. 2015 Feb;26(2):320-5. Epub 2014 Nov 17. link to original article PubMed
- Update: Jackisch C, Stroyakovskiy D, Pivot X, Ahn JS, Melichar B, Chen SC, Meyenberg C, Al-Sakaff N, Heinzmann D, Hegg R. Subcutaneous vs intravenous trastuzumab for patients with ERBB2-positive early breast cancer: final analysis of the HannaH phase 3 randomized clinical trial. JAMA Oncol. 2019 May 1;5(5):e190339. Epub 2019 May 9. link to original article link to PMC article PubMed
- CT-P6 3.2: Stebbing J, Baranau Y, Baryash V, Manikhas A, Moiseyenko V, Dzagnidze G, Zhavrid E, Boliukh D, Stroyakovskii D, Pikiel J, Eniu A, Komov D, Morar-Bolba G, Li RK, Rusyn A, Lee SJ, Lee SY, Esteva FJ. CT-P6 compared with reference trastuzumab for HER2-positive breast cancer: a randomised, double-blind, active-controlled, phase 3 equivalence trial. Lancet Oncol. 2017 Jul;18(7):917-928. Epub 2017 Jun 4. Erratum in: Lancet Oncol. 2017 Aug;18(8):e433. Erratum in: Lancet Oncol. 2017 Sep;18(9):e510. link to original article PubMed NCT02162667
- Update: Esteva FJ, Baranau YV, Baryash V, Manikhas A, Moiseyenko V, Dzagnidze G, Zhavrid E, Boliukh D, Stroyakovskiy D, Pikiel J, Eniu AE, Li RK, Rusyn AV, Tiangco B, Lee SJ, Lee SY, Yu SY, Stebbing J. Efficacy and safety of CT-P6 versus reference trastuzumab in HER2-positive early breast cancer: updated results of a randomised phase 3 trial. Cancer Chemother Pharmacol. 2019 Oct;84(4):839-847. Epub 2019 Aug 19. link to original article link to PMC article PubMed
- Update: Stebbing J, Baranau YV, Baryash V, Manikhas A, Moiseyenko V, Dzagnidze G, Zhavrid E, Boliukh D, Pikiel J, Eniu AE, Li RK, Tiangco B, Lee SJ, Kim S. Long-term efficacy and safety of CT-P6 versus trastuzumab in patients with HER2-positive early breast cancer: final results from a randomized phase III trial. Breast Cancer Res Treat. 2021 Aug;188(3):631-640. Epub 2021 Jun 20. link to original article link to PMC article PubMed
- SB3-G31-BC: Pivot X, Bondarenko I, Nowecki Z, Dvorkin M, Trishkina E, Ahn JH, Vinnyk Y, Im SA, Sarosiek T, Chatterjee S, Wojtukiewicz MZ, Moiseyenko V, Shparyk Y, Bello M 3rd, Semiglazov V, Song S, Lim J. Phase III, randomized, double-blind study comparing the efficacy, safety, and immunogenicity of SB3 (trastuzumab biosimilar) and reference trastuzumab in patients treated with neoadjuvant therapy for human epidermal growth factor receptor 2-positive early breast cancer. J Clin Oncol. 2018 Apr 1;36(10):968-974. Epub 2018 Jan 26. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02149524
TH-FEC & H (Docetaxel, SC Trastuzumab)
TH-FEC & H: Taxotere (Docetaxel) & Herceptin Hylecta (Trastuzumab and hyaluronidase), followed by Fluorouracil, Epirubicin, Cyclophosphamide, Herceptin Hylecta (Trastuzumab and hyaluronidase)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ismael et al. 2012 (HannaH) | 2009-10-19 to 2010-12-01 | Phase 3 (E-RT-switch-ic) | TH-FEC & H (IV) | Non-inferior pCR rate (co-primary endpoint) |
Chemotherapy, T portion (cycles 1 to 4)
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Chemotherapy, FEC portion (cycles 5 to 8)
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
Targeted therapy, both portions (cycles 1 to 8)
- Trastuzumab and hyaluronidase (Herceptin Hylecta) 600 mg/10,000 units SC once on day 1
21-day cycle for 8 cycles (TH x 4; FEC & H x 4)
Subsequent treatment
References
- HannaH: Ismael G, Hegg R, Muehlbauer S, Heinzmann D, Lum B, Kim SB, Pienkowski T, Lichinitser M, Semiglazov V, Melichar B, Jackisch C. Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I-III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial. Lancet Oncol. 2012 Sep;13(9):869-78. Epub 2012 Aug 9. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00950300
- Update: Jackisch C, Kim SB, Semiglazov V, Melichar B, Pivot X, Hillenbach C, Stroyakovskiy D, Lum BL, Elliott R, Weber HA, Ismael G. Subcutaneous versus intravenous formulation of trastuzumab for HER2-positive early breast cancer: updated results from the phase III HannaH study. Ann Oncol. 2015 Feb;26(2):320-5. Epub 2014 Nov 17. link to original article PubMed
- Update: Jackisch C, Stroyakovskiy D, Pivot X, Ahn JS, Melichar B, Chen SC, Meyenberg C, Al-Sakaff N, Heinzmann D, Hegg R. Subcutaneous vs intravenous trastuzumab for patients with ERBB2-positive early breast cancer: final analysis of the HannaH phase 3 randomized clinical trial. JAMA Oncol. 2019 May 1;5(5):e190339. Epub 2019 May 9. link to original article link to PMC article PubMed
TH-FEC & H (Paclitaxel)
TH-FEC & H: Taxol (Paclitaxel) & Herceptin (Trastuzumab), followed by Fluorouracil, Epirubicin, Cyclophosphamide, Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Buzdar et al. 2005 | 2001-2003 | Phase 3 (E-esc) | T-FEC | Seems to have superior pCR rate (primary endpoint) |
Chemotherapy, T portion (cycles 1 to 4)
- Paclitaxel (Taxol) 225 mg/m2 IV continuous infusion over 24 hours, started on day 1
Chemotherapy, FEC portion (cycles 5 to 8)
- Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 & 4
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
Targeted therapy, both portions
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, given prior to first dose of paclitaxel, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 2 to 8: 2 mg/kg IV once per day on days 1, 8, 15
21-day cycle for 8 cycles (TH x 4; FEC & H x 4)
Subsequent treatment
References
- Buzdar AU, Ibrahim NK, Francis D, Booser DJ, Thomas ES, Theriault RL, Pusztai L, Green MC, Arun BK, Giordano SH, Cristofanilli M, Frye DK, Smith TL, Hunt KK, Singletary SE, Sahin AA, Ewer MS, Buchholz TA, Berry D, Hortobagyi GN. Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol. 2005 Jun 1;23(16):3676-85. Epub 2005 Feb 28. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Update: Buzdar AU, Valero V, Ibrahim NK, Francis D, Broglio KR, Theriault RL, Pusztai L, Green MC, Singletary SE, Hunt KK, Sahin AA, Esteva F, Symmans WF, Ewer MS, Buchholz TA, Hortobagyi GN. Neoadjuvant therapy with paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide chemotherapy and concurrent trastuzumab in human epidermal growth factor receptor 2-positive operable breast cancer: an update of the initial randomized study population and data of additional patients treated with the same regimen. Clin Cancer Res. 2007 Jan 1;13(1):228-33. link to original article PubMed
Neoadjuvant therapy
Docetaxel & Trastuzumab (TH)
TH: Taxotere (Docetaxel) & Herceptin (Trastuzumab)
DH: Docetaxel & Herceptin (Trastuzumab)
Regimen variant #1, 75 mg/m2 q3wk docetaxel, q3wk trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Shao et al. 2020 (PEONY) | 2016-03-14 to 2017-03-13 | Phase 3 (C) | THP | Inferior pCR rate |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 4: 6 mg/kg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- Surgery, then adjuvant FEC, then adjuvant trastuzumab
Regimen variant #2, 75->100 mg/m2 q3wk docetaxel, q3wk trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gianni et al. 2011 (NeoSphere) | 2007-2009 | Randomized Phase 2 (C) | 1. Docetaxel & Pertuzumab | Not reported |
2. Pertuzumab & Trastuzumab | Not reported | |||
3. THP | Seems to have inferior pCR rate |
Note: Docetaxel dose was only escalated if tolerated.
Chemotherapy
- Docetaxel (Taxotere) as follows:
- Cycle 1: 75 mg/m2 IV once on day 1
- Cycles 2 to 4: 100 mg/m2 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 4: 6 mg/kg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
Regimen variant #3, 100 mg/m2 q3wk docetaxel, q3wk trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wu et al. 2022 (PHEDRA) | 2018-2021 | Phase 3 (C) | TH & Pyrotinib | Inferior tpCR rate |
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 4: 6 mg/kg IV once on day 1
21-day cycle for 4 cycles
Regimen variant #4, 100 mg/m2 q3wk docetaxel, weekly trastuzumab
Study | Dates of enrollment | Evidence | Efficacy |
---|---|---|---|
Van Pelt et al. 2003 | 2000-2002 | Phase 2 | OCR: 77% |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Chemotherapy
- Docetaxel (Taxotere) as follows:
- Cycles 2 to 5: 100 mg/m2 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 2 to 5: 2 mg/kg IV once per day on days 1, 8, 15
21-day cycle for 5 cycles
References
- Van Pelt AE, Mohsin S, Elledge RM, Hilsenbeck SG, Gutierrez MC, Lucci A Jr, Kalidas M, Granchi T, Scott BG, Allred DC, Chang JC. Neoadjuvant trastuzumab and docetaxel in breast cancer: preliminary results. Clin Breast Cancer. 2003 Dec;4(5):348-53. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- NeoSphere: Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, Lluch A, Staroslawska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi G, Szado T, Ratnayake J, Ross G, Valagussa P. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012 Jan;13(1):25-32. Epub 2011 Dec 6. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00545688
- Update: Gianni L, Pienkowski T, Im YH, Tseng LM, Liu MC, Lluch A, Starosławska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi GV, Magazzù D, McNally V, Douthwaite H, Ross G, Valagussa P. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 2016 Jun;17(6):791-800. Epub 2016 May 11. link to original article PubMed
- PEONY: Shao Z, Pang D, Yang H, Li W, Wang S, Cui S, Liao N, Wang Y, Wang C, Chang YC, Wang H, Kang SY, Seo JH, Shen K, Laohawiriyakamol S, Jiang Z, Li J, Zhou J, Althaus B, Mao Y, Eng-Wong J. Efficacy, Safety, and Tolerability of Pertuzumab, Trastuzumab, and Docetaxel for Patients With Early or Locally Advanced ERBB2-Positive Breast Cancer in Asia: The PEONY Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Mar 1;6(3):e193692. Epub 2020 Mar 12. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT02586025
- Update: Huang L, Pang D, Yang H, Li W, Wang S, Cui S, Liao N, Wang Y, Wang C, Chang YC, Wang HC, Kang SY, Seo JH, Shen K, Laohawiriyakamol S, Jiang Z, Wang H, Lamour F, Song G, Curran M, Duan C, Lysbet de Haas S, Restuccia E, Shao Z. Neoadjuvant-adjuvant pertuzumab in HER2-positive early breast cancer: final analysis of the randomized phase III PEONY trial. Nat Commun. 2024 Mar 9;15(1):2153. link to original article link to PMC article PubMed
- PHEDRA: Wu J, Jiang Z, Liu Z, Yang B, Yang H, Tang J, Wang K, Liu Y, Wang H, Fu P, Zhang S, Liu Q, Wang S, Huang J, Wang C, Wang S, Wang Y, Zhen L, Zhu X, Wu F, Lin X, Zou J. Neoadjuvant pyrotinib, trastuzumab, and docetaxel for HER2-positive breast cancer (PHEDRA): a double-blind, randomized phase 3 trial. BMC Med. 2022 Dec 27;20(1):498. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT03588091
Docetaxel & Trastuzumab (TH) & Pyrotinib
TH & Pyrotinib: Taxotere (Docetaxel), Herceptin (Trastuzumab), Pyrotinib
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wu et al. 2022 (PHEDRA) | 2018-2021 | Phase 3 (E-esc) | TH | Superior tpCR rate (primary endpoint) tpCR rate: 41% vs 22% |
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy
- Pyrotinib (Irene) 400 mg PO once per day
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 4: 6 mg/kg IV once on day 1
21-day cycle for 4 cycles
References
- PHEDRA: Wu J, Jiang Z, Liu Z, Yang B, Yang H, Tang J, Wang K, Liu Y, Wang H, Fu P, Zhang S, Liu Q, Wang S, Huang J, Wang C, Wang S, Wang Y, Zhen L, Zhu X, Wu F, Lin X, Zou J. Neoadjuvant pyrotinib, trastuzumab, and docetaxel for HER2-positive breast cancer (PHEDRA): a double-blind, randomized phase 3 trial. BMC Med. 2022 Dec 27;20(1):498. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT03588091
Lapatinib & Paclitaxel (TL)
TL: Taxol (Paclitaxel) & Lapatinib
Regimen variant #1, weekly paclitaxel x 12
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Baselga et al. 2012 (NeoALTTO) | 2008-2010 | Phase 3 (E-switch-ic) | See link | See link |
Preceding treatment
- Neoadjuvant Lapatinib x 6 wk
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15, 22
Targeted therapy
- Lapatinib (Tykerb) 1500 mg PO once per day
28-day cycle for 3 cycles
Regimen variant #2, weekly paclitaxel x 16
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Carey et al. 2015 (CALGB 40601) | 2008-2012 | Phase 3 (E-switch-ic) | 1. TH | Not reported |
2. THL | Not reported |
Note: this arm was closed early.
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15, 22
Targeted therapy
- Lapatinib (Tykerb) 1500 mg PO once per day
28-day cycle for 4 cycles
Subsequent treatment
- Surgery; adjuvant AC x 4 or ddAC x 4, then trastuzumab for 36 weeks was recommended but not mandated
References
- NeoALTTO: Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00553358
- Update: de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. Epub 2014 Aug 14. link to original article PubMed
- Update: Huober J, Holmes E, Baselga J, de Azambuja E, Untch M, Fumagalli D, Sarp S, Lang I, Smith I, Boyle F, Xu B, Lecocq C, Wildiers H, Jouannaud C, Hackman J, Dasappa L, Ciruelos E, Toral Pena JC, Adamchuk H, Hickish T, de la Pena L, Jackisch C, Gelber RD, Piccart-Gebhart M, Di Cosimo S. Survival outcomes of the NeoALTTO study (BIG 1-06): updated results of a randomised multicenter phase III neoadjuvant clinical trial in patients with HER2-positive primary breast cancer. Eur J Cancer. 2019 Sep;118:169-177. Epub 2019 Aug 1. link to original article PubMed
- CALGB 40601: Carey LA, Berry DA, Cirrincione CT, Barry WT, Pitcher BN, Harris LN, Ollila DW, Krop IE, Henry NL, Weckstein DJ, Anders CK, Singh B, Hoadley KA, Iglesia M, Cheang MC, Perou CM, Winer EP, Hudis CA. Molecular heterogeneity and response to neoadjuvant human epidermal growth factor receptor 2 targeting in CALGB 40601, a randomized phase III trial of paclitaxel plus trastuzumab with or without lapatinib. J Clin Oncol. 2016 Feb 20;34(6):542-9. Epub 2015 Nov 2. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00770809
- Update: Fernandez-Martinez A, Krop IE, Hillman DW, Polley MY, Parker JS, Huebner L, Hoadley KA, Shepherd J, Tolaney S, Henry NL, Dang C, Harris L, Berry D, Hahn O, Hudis C, Winer E, Partridge A, Perou CM, Carey LA. Survival, Pathologic Response, and Genomics in CALGB 40601 (Alliance), a Neoadjuvant Phase III Trial of Paclitaxel-Trastuzumab With or Without Lapatinib in HER2-Positive Breast Cancer. J Clin Oncol. 2020 Dec 10;38(35):4184-4193. Epub 2020 Oct 23. link to original article link to PMC article PubMed
Lapatinib & Trastuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Baselga et al. 2012 (NeoALTTO) | 2008-2010 | Phase 3 (E-esc) | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Targeted therapy
- Lapatinib (Tykerb) 1000 mg PO once per day
- Trastuzumab (Herceptin) 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22, 29, 36
6-week course
Subsequent treatment
- Neoadjuvant THL (Taxol) x 12 wk, then surgery
References
- NeoALTTO: Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00553358
- Update: de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. Epub 2014 Aug 14. link to original article PubMed
- Update: Huober J, Holmes E, Baselga J, de Azambuja E, Untch M, Fumagalli D, Sarp S, Lang I, Smith I, Boyle F, Xu B, Lecocq C, Wildiers H, Jouannaud C, Hackman J, Dasappa L, Ciruelos E, Toral Pena JC, Adamchuk H, Hickish T, de la Pena L, Jackisch C, Gelber RD, Piccart-Gebhart M, Di Cosimo S. Survival outcomes of the NeoALTTO study (BIG 1-06): updated results of a randomised multicenter phase III neoadjuvant clinical trial in patients with HER2-positive primary breast cancer. Eur J Cancer. 2019 Sep;118:169-177. Epub 2019 Aug 1. link to original article PubMed
TCH (Docetaxel)
TCH: Taxotere (Docetaxel), Carboplatin, Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lammers et al. 2018 (REFLECTIONS B327-04) | Not reported | Phase 3 (C) | TCH (trastuzumab-qyyp) x 6 | Non-inferior pharmacokinetics (primary endpoint) |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV over 60 minutes once on day 1, given second
- Carboplatin (Paraplatin) AUC 6 IV over at least 15 minutes once on day 1, given third
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV over 90 minutes once on day 1, given first
- Cycles 2 to 6: 6 mg/kg IV over 30 to 90 minutes once on day 1, given first
21-day cycle for 6 cycles
Subsequent treatment
References
- REFLECTIONS B327-04: Lammers PE, Dank M, Masetti R, Abbas R, Hilton F, Coppola J, Jacobs I. Neoadjuvant PF-05280014 (a potential trastuzumab biosimilar) versus trastuzumab for operable HER2+ breast cancer. Br J Cancer. 2018 Aug;119(3):266-273. Epub 2018 Jul 13. link to original article link to PMC article PubMed NCT02187744
TCHP (Paclitaxel)
TCHP: Taxol (Paclitaxel), Carboplatin, Herceptin (Trastuzumab), Pertuzumab
Regimen variant #1, standard carboplatin
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
van Ramshorst et al. 2018 (TRAIN-2) | 2013-2016 | Phase 3 (E-switch-ic) | FEC & HP x 3, then TCHP x 6 | Did not meet primary endpoint of pCR rate |
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1 & 8
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 9: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycles 2 to 9: 420 mg IV once on day 1
21-day cycle for 9 cycles
Subsequent treatment
Regimen variant #2, split carboplatin
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
van Ramshorst et al. 2018 (TRAIN-2) | 2013-2016 | Phase 3 (E-switch-ic) | FEC & HP x 3, then TCHP x 6 | Did not meet primary endpoint of pCR rate |
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1 & 8
- Carboplatin (Paraplatin) AUC 3 IV once per day on days 1 & 8
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 9: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycles 2 to 9: 420 mg IV once on day 1
21-day cycle for 9 cycles
Subsequent treatment
References
- TRAIN-2: van Ramshorst MS, van der Voort A, van Werkhoven ED, Mandjes IA, Kemper I, Dezentjé VO, Oving IM, Honkoop AH, Tick LW, van de Wouw AJ, Mandigers CM, van Warmerdam LJ, Wesseling J, Vrancken Peeters MT, Linn SC, Sonke GS; Dutch Breast Cancer Research Group. Neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2 blockade for HER2-positive breast cancer (TRAIN-2): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2018 Dec;19(12):1630-1640. Epub 2018 Nov 6. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT01996267
- Update: van der Voort A, van Ramshorst MS, van Werkhoven ED, Mandjes IA, Kemper I, Vulink AJ, Oving IM, Honkoop AH, Tick LW, van de Wouw AJ, Mandigers CM, van Warmerdam LJ, Wesseling J, Vrancken Peeters MT, Linn SC, Sonke GS. Three-Year Follow-up of Neoadjuvant Chemotherapy With or Without Anthracyclines in the Presence of Dual ERBB2 Blockade in Patients With ERBB2-Positive Breast Cancer: A Secondary Analysis of the TRAIN-2 Randomized, Phase 3 Trial. JAMA Oncol. 2021 Jul 1;7(7):978-984. link to original article link to PMC article PubMed
TCHP (Docetaxel)
TCHP: Taxotere (Docetaxel), Carboplatin, Herceptin (Trastuzumab), Pertuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Schneeweiss et al. 2013 (TRYPHAENA) | 2009-2011 | Randomized Phase 2 (E-RT-switch-ic) | 1. FEC-THP 2. FEC & HP-THP |
Not reported | Similar rates of LVSD (co-primary endpoint) |
Hurvitz et al. 2017 (KRISTINE) | 2014-06-25 to 2015-06-15 | Phase 3 (C) | Pertuzumab & T-DM1 | Superior EFS1 (secondary endpoint) (HR 0.38, 95% CI 0.20-0.74) Seems to have superior pCR rate (primary endpoint) |
1Reported efficacy for KRISTINE is based on the 2019 update.
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 6: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycles 2 to 6: 420 mg IV once on day 1
21-day cycle for 6 cycles
References
- TRYPHAENA: Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, Tausch C, Seo JH, Tsai YF, Ratnayake J, McNally V, Ross G, Cortés J. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013 Sep;24(9):2278-84. Epub 2013 May 22. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00976989
- Update: Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Waldron-Lynch M, Eng-Wong J, Kirk S, Cortés J. Long-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: Evaluating pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer. Eur J Cancer. 2018 Jan;89:27-35. Epub 2017 Dec 8. link to original article PubMed
- KRISTINE: Hurvitz SA, Martin M, Symmans WF, Jung KH, Huang CS, Thompson AM, Harbeck N, Valero V, Stroyakovskiy D, Wildiers H, Campone M, Boileau JF, Beckmann MW, Afenjar K, Fresco R, Helms HJ, Xu J, Lin YG, Sparano J, Slamon D. Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2018 Jan;19(1):115-126. Epub 2017 Nov 23. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT02131064
- Update: Hurvitz SA, Martin M, Jung KH, Huang CS, Harbeck N, Valero V, Stroyakovskiy D, Wildiers H, Campone M, Boileau JF, Fasching PA, Afenjar K, Spera G, Lopez-Valverde V, Song C, Trask P, Boulet T, Sparano JA, Symmans WF, Thompson AM, Slamon D. Neoadjuvant trastuzumab emtansine and pertuzumab in human epidermal growth factor receptor 2-positive breast cancer: three-year outcomes from the phase III KRISTINE Study. J Clin Oncol. 2019 Sep 1;37(25):2206-2216. Epub 2019 Jun 3. link to original article link to PMC article PubMed
TCHP (Docetaxel, SC Trastuzumab)
TCHP: Taxotere (Docetaxel), Carboplatin, Herceptin Hylecta (SC Trastuzumab), Pertuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pérez-García et al. 2021 (PHERGain) | 2017-06-26 to 2019-04-24 | Randomized Phase 2 (C) | HP, then PET-adapted therapy | Non-comparative |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
Targeted therapy
- Trastuzumab and hyaluronidase (Herceptin Hylecta) 600 mg SC once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycles 2 to 6: 420 mg IV once on day 1
21-day cycle for 6 cycles
Subsequent treatment
References
- PHERGain: Pérez-García JM, Gebhart G, Ruiz Borrego M, Stradella A, Bermejo B, Schmid P, Marmé F, Escrivá-de-Romani S, Calvo L, Ribelles N, Martinez N, Albacar C, Prat A, Dalenc F, Kerrou K, Colleoni M, Afonso N, Di Cosimo S, Sampayo-Cordero M, Malfettone A, Cortés J, Llombart-Cussac A; PHERGain steering committee and trial investigators. Chemotherapy de-escalation using an 18F-FDG-PET-based pathological response-adapted strategy in patients with HER2-positive early breast cancer (PHERGain): a multicentre, randomised, open-label, non-comparative, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):858-871. Epub 2021 May 18. link to original article PubMed NCT03161353
- Update: Pérez-García JM, Cortés J, Ruiz-Borrego M, Colleoni M, Stradella A, Bermejo B, Dalenc F, Escrivá-de-Romaní S, Calvo Martínez L, Ribelles N, Marmé F, Cortés A, Albacar C, Gebhart G, Prat A, Kerrou K, Schmid P, Braga S, Di Cosimo S, Gion M, Antonarelli G, Popa C, Szostak E, Alcalá-López D, Gener P, Rodríguez-Morató J, Mina L, Sampayo-Cordero M, Llombart-Cussac A; PHERGain Trial Investigators. 3-year invasive disease-free survival with chemotherapy de-escalation using an 18F-FDG-PET-based, pathological complete response-adapted strategy in HER2-positive early breast cancer (PHERGain): a randomised, open-label, phase 2 trial. Lancet. 2024 Apr 27;403(10437):1649-1659. Epub 2024 Apr 3. link to original article dosing details in abstract have been reviewed by our editors PubMed
Paclitaxel & Trastuzumab (TH)
TH: Taxol (Paclitaxel) & Herceptin (Trastuzumab)
T-T: Taxol (Paclitaxel) & Trastuzumab
Regimen variant #1, weekly paclitaxel x 12, weekly trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Baselga et al. 2012 (NeoALTTO) | 2008-2010 | Phase 3 (C) | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. Patients in NeoALTTO had already undergone trastuzumab loading so would continue at the 2 mg/kg weekly dose.
Preceding treatment
- NeoALTTO: Neoadjvuant Trastuzumab x 6 wk
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 2 to 4: 2 mg/kg IV once per day on days 1, 8, 15
21-day cycle for 4 cycles
Regimen variant #2, weekly paclitaxel x 12, q3wk trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2018 (LILAC) | 2013-2015 | Phase 3 (C) | Paclitaxel & Trastuzumab-anns | Inconclusive whether equivalent pCR rate |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Neoadjuvant anthracycline-containing chemotherapy x 4
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 4: 6 mg/kg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
Regimen variant #3, weekly paclitaxel x 16
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Carey et al. 2015 (CALGB 40601) | 2008-2012 | Phase 3 (C) | 1. THL | Did not meet primary endpoint of pCR rate |
2. TL | Not reported |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15, 22
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22
- Cycles 2 to 4: 2 mg/kg IV once per day on days 1, 8, 15, 22
28-day cycle for 4 cycles
Subsequent treatment
- Surgery, then adjuvant AC x 4 or ddAC x 4, then trastuzumab for 36 weeks was recommended but not mandated
Regimen variant #4, q3wk, paclitaxel 175 mg/m2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2018 (LILAC) | 2013-2015 | Phase 3 (C) | Paclitaxel & Trastuzumab-anns | Inconclusive whether equivalent pCR rate |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Neoadjuvant anthracycline-containing chemotherapy x 4
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once
- Cycles 2 to 4: 6 mg/kg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
References
- NeoALTTO: Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00553358
- Update: de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. Epub 2014 Aug 14. link to original article PubMed
- Update: Huober J, Holmes E, Baselga J, de Azambuja E, Untch M, Fumagalli D, Sarp S, Lang I, Smith I, Boyle F, Xu B, Lecocq C, Wildiers H, Jouannaud C, Hackman J, Dasappa L, Ciruelos E, Toral Pena JC, Adamchuk H, Hickish T, de la Pena L, Jackisch C, Gelber RD, Piccart-Gebhart M, Di Cosimo S. Survival outcomes of the NeoALTTO study (BIG 1-06): updated results of a randomised multicenter phase III neoadjuvant clinical trial in patients with HER2-positive primary breast cancer. Eur J Cancer. 2019 Sep;118:169-177. Epub 2019 Aug 1. link to original article PubMed
- CALGB 40601: Carey LA, Berry DA, Cirrincione CT, Barry WT, Pitcher BN, Harris LN, Ollila DW, Krop IE, Henry NL, Weckstein DJ, Anders CK, Singh B, Hoadley KA, Iglesia M, Cheang MC, Perou CM, Winer EP, Hudis CA. Molecular heterogeneity and response to neoadjuvant human epidermal growth factor receptor 2 targeting in CALGB 40601, a randomized phase III trial of paclitaxel plus trastuzumab with or without lapatinib. J Clin Oncol. 2016 Feb 20;34(6):542-9. Epub 2015 Nov 2. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00770809
- Update: Fernandez-Martinez A, Krop IE, Hillman DW, Polley MY, Parker JS, Huebner L, Hoadley KA, Shepherd J, Tolaney S, Henry NL, Dang C, Harris L, Berry D, Hahn O, Hudis C, Winer E, Partridge A, Perou CM, Carey LA. Survival, Pathologic Response, and Genomics in CALGB 40601 (Alliance), a Neoadjuvant Phase III Trial of Paclitaxel-Trastuzumab With or Without Lapatinib in HER2-Positive Breast Cancer. J Clin Oncol. 2020 Dec 10;38(35):4184-4193. Epub 2020 Oct 23. link to original article link to PMC article PubMed
- I-SPY 2 neratinib: Park JW, Liu MC, Yee D, Yau C, van 't Veer LJ, Symmans WF, Paoloni M, Perlmutter J, Hylton NM, Hogarth M, DeMichele A, Buxton MB, Chien AJ, Wallace AM, Boughey JC, Haddad TC, Chui SY, Kemmer KA, Kaplan HG, Isaacs C, Nanda R, Tripathy D, Albain KS, Edmiston KK, Elias AD, Northfelt DW, Pusztai L, Moulder SL, Lang JE, Viscusi RK, Euhus DM, Haley BB, Khan QJ, Wood WC, Melisko M, Schwab R, Helsten T, Lyandres J, Davis SE, Hirst GL, Sanil A, Esserman LJ, Berry DA; I-SPY 2 Investigators. Adaptive randomization of neratinib in early breast cancer. N Engl J Med. 2016 Jul 7;375(1):11-22. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01042379
- LILAC: von Minckwitz G, Colleoni M, Kolberg HC, Morales S, Santi P, Tomasevic Z, Zhang N, Hanes V. Efficacy and safety of ABP 980 compared with reference trastuzumab in women with HER2-positive early breast cancer (LILAC study): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2018 Jul;19(7):987-998. Epub 2018 Jun 4. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT01901146
THL (Paclitaxel)
THL: Taxol (Paclitaxel), Herceptin (Trastuzumab), Lapatinib
Regimen variant #1, weekly paclitaxel x 12
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Baselga et al. 2012 (NeoALTTO) | 2008-2010 | Phase 3 (E-esc) | See link | See link |
Preceding treatment
- Neoadjuvant Lapatinib & Trastuzumab x 6 wk
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15, 22
Targeted therapy
- Trastuzumab (Herceptin) 2 mg/kg IV once per day on days 1, 8, 15, 22
- Lapatinib (Tykerb) 1000 mg PO once per day
28-day cycle for 3 cycles
Regimen variant #2, weekly paclitaxel x 16
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Carey et al. 2015 (CALGB 40601) | 2008-2012 | Phase 3 (E-esc) | 1. TH | Did not meet primary endpoint of pCR rate |
2. TL | Not reported |
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15, 22
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22
- Cycles 2 to 4: 2 mg/kg IV once per day on days 1, 8, 15, 22
- Lapatinib (Tykerb) 750 mg PO once per day
28-day cycle for 4 cycles
Subsequent treatment
- Surgery; adjuvant AC x 4 or ddAC x 4, then trastuzumab for 36 weeks was recommended but not mandated
References
- NeoALTTO: Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00553358
- Update: de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. Epub 2014 Aug 14. link to original article PubMed
- Update: Huober J, Holmes E, Baselga J, de Azambuja E, Untch M, Fumagalli D, Sarp S, Lang I, Smith I, Boyle F, Xu B, Lecocq C, Wildiers H, Jouannaud C, Hackman J, Dasappa L, Ciruelos E, Toral Pena JC, Adamchuk H, Hickish T, de la Pena L, Jackisch C, Gelber RD, Piccart-Gebhart M, Di Cosimo S. Survival outcomes of the NeoALTTO study (BIG 1-06): updated results of a randomised multicenter phase III neoadjuvant clinical trial in patients with HER2-positive primary breast cancer. Eur J Cancer. 2019 Sep;118:169-177. Epub 2019 Aug 1. link to original article PubMed
- CALGB 40601: Carey LA, Berry DA, Cirrincione CT, Barry WT, Pitcher BN, Harris LN, Ollila DW, Krop IE, Henry NL, Weckstein DJ, Anders CK, Singh B, Hoadley KA, Iglesia M, Cheang MC, Perou CM, Winer EP, Hudis CA. Molecular heterogeneity and response to neoadjuvant human epidermal growth factor receptor 2 targeting in CALGB 40601, a randomized phase III trial of paclitaxel plus trastuzumab with or without lapatinib. J Clin Oncol. 2016 Feb 20;34(6):542-9. Epub 2015 Nov 2. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00770809
- Update: Fernandez-Martinez A, Krop IE, Hillman DW, Polley MY, Parker JS, Huebner L, Hoadley KA, Shepherd J, Tolaney S, Henry NL, Dang C, Harris L, Berry D, Hahn O, Hudis C, Winer E, Partridge A, Perou CM, Carey LA. Survival, Pathologic Response, and Genomics in CALGB 40601 (Alliance), a Neoadjuvant Phase III Trial of Paclitaxel-Trastuzumab With or Without Lapatinib in HER2-Positive Breast Cancer. J Clin Oncol. 2020 Dec 10;38(35):4184-4193. Epub 2020 Oct 23. link to original article link to PMC article PubMed
THP (Docetaxel)
THP: Taxotere (Docetaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gianni et al. 2011 (NeoSphere) | 2007-2009 | Randomized Phase 2 (E-RT-esc) | 1. Docetaxel & Pertuzumab | Did not meet primary endpoint of pCR rate |
2. Pertuzumab & Trastuzumab | Did not meet primary endpoint of pCR rate | |||
3. TH | Seems to have superior pCR rate (primary endpoint) | |||
Shao et al. 2020 (PEONY) | 2016-03-14 to 2017-03-13 | Phase 3 (E-esc) | TH | Superior pCR rate (primary endpoint) Superior DFS601 (secondary endpoint) DFS60: 86% vs 75% (HR 0.52, 95% CI 0.30-0.88) |
1Reported efficacy for PEONY is based on the 2024 update.
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 4: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycles 2 to 4: 420 mg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- NeoSphere: Surgery
- PEONY: Surgery, then adjuvant FEC, then adjuvant Pertuzumab & Trastuzumab
Dose and schedule modifications
- Based on tolerability, investigators could increase docetaxel dose to 100 mg/m2 IV once on day 1 in cycles 2 to 4
References
- NeoSphere: Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, Lluch A, Staroslawska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi G, Szado T, Ratnayake J, Ross G, Valagussa P. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012 Jan;13(1):25-32. Epub 2011 Dec 6. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00545688
- Update: Gianni L, Pienkowski T, Im YH, Tseng LM, Liu MC, Lluch A, Starosławska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi GV, Magazzù D, McNally V, Douthwaite H, Ross G, Valagussa P. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 2016 Jun;17(6):791-800. Epub 2016 May 11. link to original article PubMed
- PEONY: Shao Z, Pang D, Yang H, Li W, Wang S, Cui S, Liao N, Wang Y, Wang C, Chang YC, Wang H, Kang SY, Seo JH, Shen K, Laohawiriyakamol S, Jiang Z, Li J, Zhou J, Althaus B, Mao Y, Eng-Wong J. Efficacy, Safety, and Tolerability of Pertuzumab, Trastuzumab, and Docetaxel for Patients With Early or Locally Advanced ERBB2-Positive Breast Cancer in Asia: The PEONY Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Mar 1;6(3):e193692. Epub 2020 Mar 12. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT02586025
- Update: Huang L, Pang D, Yang H, Li W, Wang S, Cui S, Liao N, Wang Y, Wang C, Chang YC, Wang HC, Kang SY, Seo JH, Shen K, Laohawiriyakamol S, Jiang Z, Wang H, Lamour F, Song G, Curran M, Duan C, Lysbet de Haas S, Restuccia E, Shao Z. Neoadjuvant-adjuvant pertuzumab in HER2-positive early breast cancer: final analysis of the randomized phase III PEONY trial. Nat Commun. 2024 Mar 9;15(1):2153. link to original article link to PMC article PubMed
Trastuzumab monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Baselga et al. 2012 (NeoALTTO) | 2008-2010 | Phase 3 (C) | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Targeted therapy
- Trastuzumab (Herceptin) 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22, 29, 36
6-week course
Subsequent treatment
- Neoadjuvant TH (Paclitaxel) x 12 wk, then surgery
References
- NeoALTTO: Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00553358
- Update: de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. Epub 2014 Aug 14. link to original article PubMed
- Update: Huober J, Holmes E, Baselga J, de Azambuja E, Untch M, Fumagalli D, Sarp S, Lang I, Smith I, Boyle F, Xu B, Lecocq C, Wildiers H, Jouannaud C, Hackman J, Dasappa L, Ciruelos E, Toral Pena JC, Adamchuk H, Hickish T, de la Pena L, Jackisch C, Gelber RD, Piccart-Gebhart M, Di Cosimo S. Survival outcomes of the NeoALTTO study (BIG 1-06): updated results of a randomised multicenter phase III neoadjuvant clinical trial in patients with HER2-positive primary breast cancer. Eur J Cancer. 2019 Sep;118:169-177. Epub 2019 Aug 1. link to original article PubMed
Neoadjuvant response criteria
Clinical response rate (cRR)
Although fairly dated, some trials such as ACOSOG Z1031 make use of the WHO criteria for response to neoadjuvant therapy. Included here primarily for historical purposes.
References
- Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer. 1981 Jan 1;47(1):207-14. link to original article PubMed
Miller-Payne scoring system
- Grade 1: No change or some changes to individual malignant cells, but no reduction in overall cellularity
- Grade 2: Minor loss of tumor cells (up to 30%), but overall cellularity still high
- Grade 3: An estimated 30 to 90% reduction in the number of tumor cells
- Grade 4: Marked disappearance of tumor cells such that only small clusters or widely dispersed individual cells remain (loss of greater than 90% of tumor cells)
- Grade 5: No invasive cancer cells identifiable in sections from the site of the tumor (carcinoma in situ may be present)
References
- Ogston KN, Miller ID, Payne S, Hutcheon AW, Sarkar TK, Smith I, Schofield A, Heys SD. A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast. 2003 Oct;12(5):320-7. link to original article PubMed
Residual cancer burden (RCB)
- The RCB is calculated as follows: RCB = 1.4 (finv*dprim)0.17 + [4(1 - 0.75LN)dmet]0.17
- where dprim is derived from the bidimensional diameters of the primary tumor bed in the resected specimen, finv is the proportion of the primary tumor bed that contains invasive carcinoma, LN is the number of axillary lymph nodes containing metastatic carcinoma, and dmet is the diameter of the largest metastasis in an axillary lymph node.
- The cut-off points are 1.36 and 3.28.
References
- Symmans WF, Peintinger F, Hatzis C, Rajan R, Kuerer H, Valero V, Assad L, Poniecka A, Hennessy B, Green M, Buzdar AU, Singletary SE, Hortobagyi GN, Pusztai L. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol. 2007 Oct 1;25(28):4414-22. Epub 2007 Sep 4. link to original article PubMed
Residual disease in breast and nodes (RDBN)
- Level 1: pCR in breast and nodes with or without in situ carcinoma
- Levels 2 to 4: Residual disease, calculated as 0.2 (residual breast tumor size in cm) + index of involved nodes (0 for no positive nodes, 1 for 1 to 4 positive nodes, 2 for 5 to 7 positive nodes, and 3 for 8 positive nodes) + the Scarff–Bloom–Richardson grade (1, 2, or 3). The cut-off points are 3 and 4.3.
References
- Chollet P, Abrial C, Durando X, Thivat E, Tacca O, Mouret-Reynier MA, Leheurteur M, Kwiatkowski F, Dauplat J, Penault-Llorca F. A new prognostic classification after primary chemotherapy for breast cancer: residual disease in breast and nodes (RDBN). Cancer J. 2008 Mar-Apr;14(2):128-32. link to original article PubMed
Sataloff's classification
- Breast:
- T-A: Total or nearly total therapeutic effect
- T-B: Greater than 50% therapeutic effect
- T-C: Less than 50% therapeutic effect
- T-D: No therapeutic effect
- Lymph node:
- N-A: Therapeutic effect but no metastasis
- N-B: No metastasis, no therapeutic effect
- N-C: Therapeutic effect but metastasis
- N-D: Metastasis, no therapeutic effect
References
- Sataloff DM, Mason BA, Prestipino AJ, Seinige UL, Lieber CP, Baloch Z. Pathologic response to induction chemotherapy in locally advanced carcinoma of the breast: a determinant of outcome. J Am Coll Surg. 1995 Mar;180(3):297-306. PubMed
Tumor response ratio
Calculated as follows: Residual breast disease observed upon pathologic examination divided by the size of the tumor on the pre-neoadjuvant therapy image.
- TRR = 0: pathologic complete response (pCR)
- TRR greater than 0 up to 0.4: strong partial response
- TRR greater than 0.4 up to 1.0: weak partial response (WPR)
- TRR greater than 1.0: tumor growth
References
- Miller M, Ottesen RA, Niland JC, Kruper L, Chen SL, Vito C. Tumor response ratio predicts overall survival in breast cancer patients treated with neoadjuvant chemotherapy. Ann Surg Oncol. 2014 Oct;21(10):3317-23. Epub 2014 Jul 25. link to original article PubMed
ypTNM staging
This system is proprietary to the AJCC. Please visit their site or consult the AJCC Manual for further details.
Adjuvant therapy, sequential regimens
AC-H
AC-H: Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Herceptin (Trastuzumab)
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sawaki et al. 2020 (RESPECT) | 2009-10 to 2014-11 | Randomized (C) | Trastuzumab x 1 y | Inconclusive whether non-inferior DFS (primary endpoint) |
Preceding treatment
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Targeted therapy, H portion (cycles 5 to 22)
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
21-day cycle for 22 cycles (AC x 4; H x 18)
Regimen variant #2, weekly trastuzumab
Study | Dates of enrollment | Evidence |
---|---|---|
Van Pelt et al. 2003 | 2000-2002 | Phase 2 |
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Targeted therapy, H portion (cycles 5 to 56)
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 4 mg/kg IV once on day 1
- Cycles 6 to 56: 2 mg/kg IV once on day 1
21-day cycle for 4 cycles, then 7-day cycle for 52 cycles (AC x 4; H x 52)
References
- Van Pelt AE, Mohsin S, Elledge RM, Hilsenbeck SG, Gutierrez MC, Lucci A Jr, Kalidas M, Granchi T, Scott BG, Allred DC, Chang JC. Neoadjuvant trastuzumab and docetaxel in breast cancer: preliminary results. Clin Breast Cancer. 2003 Dec;4(5):348-53. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- RESPECT: Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. link to original article dosing details in supplement have been reviewed by our editors PubMed NCT01104935
AC-TH (Paclitaxel)
AC-TH: Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxol (Paclitaxel) & Herceptin (Trastuzumab)
Regimen variant #1, weekly paclitaxel, q3wk trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for AC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
21-day cycle for 22 cycles (AC x 4; TH x 4)
Regimen variant #2, weekly paclitaxel, weekly trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Romond et al. 2005 (NCCTG N9831) | 2000-2005 | Phase 3 (E-RT-esc) | 1. AC-T; weekly paclitaxel | Superior OS1 (secondary endpoint) OS120: 84% vs 75.2% (HR 0.63, 95% CI 0.5-0.73) |
2. AC-T-H | Might have superior DFS2 (primary endpoint) |
1Reported efficacy is based on the 2014 pooled update.
2Reported efficacy is based on the 2011 update.
Preceding treatment
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 6 to 22: 2 mg/kg IV once per day on days 1, 8, 15
21-day cycle for 22 cycles (AC x 4; TH x 4)
Regimen variant #3, q3wk paclitaxel, weekly trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Romond et al. 2005 (NSABP B-31) | 2000-2005 | Phase 3 (E-RT-esc) | 1a. AC-T; weekly paclitaxel 1b. AC-T; q3wk paclitaxel |
Superior OS1 (secondary endpoint) OS120: 84% vs 75.2% (HR 0.63, 95% CI 0.5-0.73) Superior DFS (primary endpoint) |
Might have superior DASI score |
1Reported efficacy is based on the 2014 pooled update.
Preceding treatment
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 5 to 8)
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 6 to 22: 2 mg/kg IV once per day on days 1, 8, 15
21-day cycle for 22 cycles (AC x 4; TH x 4)
References
- NSABP B-31: Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1673-84. link to original article PubMed NCT00004067
- Pooled update: Perez EA, Romond EH, Suman VJ, Jeong JH, Davidson NE, Geyer CE Jr, Martino S, Mamounas EP, Kaufman PA, Wolmark N. Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31. J Clin Oncol. 2011 Sep 1;29(25):3366-73. Epub 2011 Jul 18. link to original article link to PMC article PubMed
- Pooled update: Perez EA, Romond EH, Suman VJ, Jeong JH, Sledge G, Geyer CE Jr, Martino S, Rastogi P, Gralow J, Swain SM, Winer EP, Colon-Otero G, Davidson NE, Mamounas E, Zujewski JA, Wolmark N. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 2014 Nov 20;32(33):3744-52. Epub 2014 Oct 20. link to original article link to PMC article PubMed
- HRQoL analysis: Ganz PA, Romond EH, Cecchini RS, Rastogi P, Geyer CE Jr, Swain SM, Jeong JH, Fehrenbacher L, Gross HM, Brufsky AM, Flynn PJ, Wahl TA, Seay TE, Wade JL 3rd, Biggs DD, Atkins JN, Polikoff J, Zapas JL, Mamounas EP, Wolmark N. Long-term follow-up of cardiac function and quality of life for patients in NSABP protocol B-31/NRG Oncology: a randomized trial comparing the safety and efficacy of doxorubicin and cyclophosphamide (AC) followed by paclitaxel with AC followed by paclitaxel and trastuzumab in patients with node-positive breast cancer with tumors overexpressing human epidermal growth factor receptor 2. J Clin Oncol. 2017 Dec 10;35(35):3942-3948. Epub 2017 Oct 26. link to original article link to PMC article PubMed
- NCCTG N9831: Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1673-84. link to original article PubMed NCT00005970
- Pooled update: Perez EA, Romond EH, Suman VJ, Jeong JH, Davidson NE, Geyer CE Jr, Martino S, Mamounas EP, Kaufman PA, Wolmark N. Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31. J Clin Oncol. 2011 Sep 1;29(25):3366-73. Epub 2011 Jul 18. link to original article link to PMC article PubMed
- Update: Perez EA, Suman VJ, Davidson NE, Gralow JR, Kaufman PA, Visscher DW, Chen B, Ingle JN, Dakhil SR, Zujewski J, Moreno-Aspitia A, Pisansky TM, Jenkins RB. Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer. J Clin Oncol. 2011 Dec 1;29(34):4491-7. Epub 2011 Oct 31. link to original article link to PMC article PubMed
- Pooled update: Perez EA, Romond EH, Suman VJ, Jeong JH, Sledge G, Geyer CE Jr, Martino S, Rastogi P, Gralow J, Swain SM, Winer EP, Colon-Otero G, Davidson NE, Mamounas E, Zujewski JA, Wolmark N. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 2014 Nov 20;32(33):3744-52. Epub 2014 Oct 20. link to original article link to PMC article PubMed
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
ddAC-ddTH (Paclitaxel)
ddAC-ddTH: dose-dense Adriamycin (Doxorubicin) and Cyclophosphamide, followed by dose-dense Taxol (Paclitaxel) & Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Dang et al. 2008 | 2005 | Phase 2 |
Preceding treatment
Chemotherapy, ddAC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Chemotherapy, ddTH portion (cycles 5 to 8)
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
Targeted therapy, ddTH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 4 mg/kg IV once on day 1, then 2 mg/kg IV once on day 8
- Cycles 6 to 8: 2 mg/kg IV once per day on days 1 & 8
- Cycles 9 to 53: 2 mg/kg IV once on day 1
Supportive therapy, both portions (cycles 1 to 8)
- Pegfilgrastim (Neulasta) 6 mg SC once on day 2, given 24 hours after chemotherapy
14-day cycle for 8 cycles (ddAC x 4; ddTH x 4)
Subsequent treatment
- Trastuzumab maintenance x 44 weeks (1 year total)
References
- Dang C, Fornier M, Sugarman S, Troso-Sandoval T, Lake D, D'Andrea G, Seidman A, Sklarin N, Dickler M, Currie V, Gilewski T, Moynahan ME, Drullinsky P, Robson M, Wasserheit-Leiblich C, Mills N, Steingart R, Panageas K, Norton L, Hudis C. The safety of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel with trastuzumab in HER-2/neu overexpressed/amplified breast cancer. J Clin Oncol. 2008 Mar 10;26(8):1216-22. link to original article dosing details in manuscript have been reviewed by our editors PubMed
AC-TH (Docetaxel)
AC-TH: Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxotere (Docetaxel) & Herceptin (Trastuzumab)
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for AC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 5 to 8)
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
21-day cycle for 22 cycles (AC x 4; TH x 4)
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for AC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 5 to 7)
- Docetaxel (Taxotere) as follows:
- Cycle 5: 75 mg/m2 IV once on day 1
- Cycles 6 & 7: 100 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
21-day cycle for 22 cycles (AC x 4; TH x 3)
Regimen variant #3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for AC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 5 to 7)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
21-day cycle for 22 cycles (AC x 4; TH x 3)
Regimen variant #4
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Slamon et al. 2011 (BCIRG 006) | 2001-2004 | Phase 3 (E-RT-esc) | 1. AC-D | Superior OS (secondary endpoint) |
2. TCH | Did not meet primary endpoint of DFS |
Preceding treatment
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 5 to 8)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 6 to 8: 2 mg/kg IV once per day on days 1, 8, 15
- Cycles 9 to 21: 6 mg/kg IV once on day 1
21-day cycle for 21 cycles (AC x 4; TH x 4)
References
- BCIRG 006: Slamon D, Eiermann W, Robert N, Pienkowski T, Martín M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J; Breast Cancer International Research Group. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011 Oct 6;365(14):1273-83. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00021255
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
AC-THP (Paclitaxel)
AC-THP: Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxol (Paclitaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-01 to 2015-06 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for AC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, THP portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, THP portion (cycles 5 to 22)
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
21-day cycle for 22 cycles (AC x 4; THP x 4)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
- KAITLIN: Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. link to original article dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01966471
AC-THP (Docetaxel)
AC-THP: Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxotere (Docetaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-01 to 2015-06 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for AC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, THP portion (cycles 5 to 8)
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy, THP portion (cycles 5 to 22)
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
21-day cycle for 22 cycles (AC x 4; THP x 4)
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-01 to 2015-06 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for AC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, THP portion (cycles 5 to 7)
- Docetaxel (Taxotere) as follows:
- Cycle 5: 75 mg/m2 IV once on day 1
- Cycles 6 & 7: 100 mg/m2 IV once on day 1
Targeted therapy, THP portion (cycles 5 to 22)
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
21-day cycle for 22 cycles (AC x 4; THP x 3)
Regimen variant #3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-01 to 2015-06 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for AC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, THP portion (cycles 5 to 7)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, THP portion (cycles 5 to 22)
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
21-day cycle for 22 cycles (AC x 4; THP x 3)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
- KAITLIN: Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. link to original article dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01966471
ddAC-TH (Paclitaxel)
ddAC-TH: dose-dense Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxol (Paclitaxel) & Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, ddAC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddAC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, TH portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
ddAC-TH (Docetaxel)
ddAC-TH: dose-dense Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxotere (Docetaxel) & Herceptin (Trastuzumab)
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, ddAC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddAC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, TH portion (cycles 5 to 8)
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, ddAC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddAC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, TH portion
- Docetaxel (Taxotere) as follows:
- Cycle 5: 75 mg/m2 IV once on day 1
- Cycles 6 & 7: 100 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
Regimen variant #3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, ddAC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddAC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, TH portion (cycles 5 to 7)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
ddAC-THP (Paclitaxel)
ddAC-THP: dose-dense Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxol (Paclitaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-01 to 2015-06 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, ddAC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddAC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, THP portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, THP portion (cycles 5 to 22)
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
- KAITLIN: Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. link to original article dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01966471
ddAC-THP (Docetaxel)
ddAC-THP: dose-dense Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxotere (Docetaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-01 to 2015-06 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, ddAC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddAC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, THP portion (cycles 5 to 8)
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy, THP portion (cycles 5 to 22)
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-01 to 2015-06 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, ddAC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddAC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, THP portion (cycles 5 to 7)
- Docetaxel (Taxotere) as follows:
- Cycle 5: 75 mg/m2 IV once on day 1
- Cycles 6 & 7: 100 mg/m2 IV once on day 1
Targeted therapy, THP portion (cycles 5 to 22)
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
Regimen variant #3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-01 to 2015-06 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, ddAC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddAC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, THP portion (cycles 5 to 7)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, THP portion (cycles 5 to 22)
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
- KAITLIN: Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. link to original article dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01966471
CMF-H
CMF-H: Cyclophosphamide, Methotrexate, Fluorouracil, followed by Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sawaki et al. 2020 (RESPECT) | 2009-10 to 2014-11 | Randomized (C) | Trastuzumab x 1 y | Inconclusive whether non-inferior DFS (primary endpoint) |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm. The protocol document reported a flat dose of oral cyclophosphamide, but this would not be consistent with any other known CMF variants; dosing below is provided as BSA-based.
Preceding treatment
Chemotherapy, CMF portion (cycles 1 to 6)
- Cyclophosphamide (Cytoxan) 75 to 100 mg/m2 PO once per day on days 1 to 14
- Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once per day on days 1 & 8
Targeted therapy, H portion (cycles 7 to 24)
- Trastuzumab (Herceptin) as follows:
- Cycle 7: 8 mg/kg IV once on day 1
- Cycles 8 to 24: 6 mg/kg IV once on day 1
21-day cycle for 24 cycles (CMF x 6; H x 18)
References
- RESPECT: Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. link to original article dosing details in supplement have been reviewed by our editors PubMed NCT01104935
EC-H
EC-H: Epirubicin and Cyclophosphamide, followed by Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sawaki et al. 2020 (RESPECT) | 2009-10 to 2014-11 | Randomized (C) | Trastuzumab x 1 y | Inconclusive whether non-inferior DFS (primary endpoint) |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Preceding treatment
Chemotherapy, EC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Targeted therapy, H portion (cycles 5 to 22)
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
21-day cycle for 22 cycles (EC x 4; H x 18)
References
- RESPECT: Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. link to original article dosing details in supplement have been reviewed by our editors PubMed NCT01104935
EC-TH (Paclitaxel)
EC-TH: Epirubicin and Cyclophosphamide, followed by Taxol (Paclitaxel) & Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for EC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, EC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
21-day cycle for 22 cycles (EC x 4; TH x 4)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
EC-TH (Docetaxel)
EC-TH: Epirubicin and Cyclophosphamide, followed by Taxotere (Docetaxel) & Herceptin (Trastuzumab)
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for EC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, EC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 5 to 8)
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
21-day cycle for 22 cycles (EC x 4; TH x 4)
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for EC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, EC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 5 to 7)
- Docetaxel (Taxotere) as follows:
- Cycle 5: 75 mg/m2 IV once on day 1
- Cycles 6 & 7: 100 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
21-day cycle for 22 cycles (EC x 4; TH x 3)
Regimen variant #3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for EC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, EC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 5 to 7)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
21-day cycle for 22 cycles (EC x 4; TH x 3)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
EC-THP (Paclitaxel)
EC-THP: Epirubicin and Cyclophosphamide, followed by Taxol (Paclitaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-01 to 2015-06 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for EC are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m2 of epirubicin per cycle.
Preceding treatment
Chemotherapy, EC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, THP portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, THP portion (cycles 5 to 22)
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
21-day cycle for 22 cycles (EC x 4; THP x 4)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
- KAITLIN: Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. link to original article dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01966471
EC-THP (Docetaxel)
EC-THP: Epirubicin and Cyclophosphamide, followed by Taxotere (Docetaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-01 to 2015-06 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for EC are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m2 of epirubicin per cycle.
Preceding treatment
Chemotherapy, EC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, THP portion (cycles 5 to 8)
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy, THP portion (cycles 5 to 22)
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
21-day cycle for 22 cycles (EC x 4; THP x 4)
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-01 to 2015-06 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for EC are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m2 of epirubicin per cycle.
Preceding treatment
Chemotherapy, EC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, THP portion (cycles 5 to 7)
- Docetaxel (Taxotere) as follows:
- Cycle 5: 75 mg/m2 IV once on day 1
- Cycles 6 & 7: 100 mg/m2 IV once on day 1
Targeted therapy, THP portion (cycles 5 to 22)
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
21-day cycle for 22 cycles (EC x 4; THP x 3)
Regimen variant #3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-01 to 2015-06 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for EC are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m2 of epirubicin per cycle.
Preceding treatment
Chemotherapy, EC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, THP portion (cycles 5 to 7)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, THP portion (cycles 5 to 22)
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
21-day cycle for 22 cycles (EC x 4; THP x 3)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
- KAITLIN: Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. link to original article dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01966471
ddEC-TH (Paclitaxel)
ddEC-TH: dose-dense Epirubicin and Cyclophosphamide, followed by Taxol (Paclitaxel) & Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddEC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, ddEC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddEC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, TH portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
ddEC-TH (Docetaxel)
ddEC-TH: dose-dense Epirubicin and Cyclophosphamide, followed by Taxotere (Docetaxel) & Herceptin (Trastuzumab)
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddEC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, ddEC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddEC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, TH portion (cycles 5 to 8)
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddEC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, ddEC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddEC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, TH portion
- Docetaxel (Taxotere) as follows:
- Cycle 5: 75 mg/m2 IV once on day 1
- Cycles 6 & 7: 100 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
Regimen variant #3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddEC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, ddEC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddEC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, TH portion (cycles 5 to 7)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
ddEC-THP (Paclitaxel)
ddEC-THP: dose-dense Epirubicin and Cyclophosphamide, followed by Taxol (Paclitaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-01 to 2015-06 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddEC are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m2 of epirubicin per cycle.
Preceding treatment
Chemotherapy, ddEC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddEC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, THP portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, THP portion (cycles 5 to 22)
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
- KAITLIN: Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. link to original article dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01966471
ddEC-THP (Docetaxel)
ddEC-THP: dose-dense Epirubicin and Cyclophosphamide, followed by Taxotere (Docetaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-01 to 2015-06 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddEC are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m2 of epirubicin per cycle.
Preceding treatment
Chemotherapy, ddEC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddEC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, THP portion (cycles 5 to 8)
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy, THP portion (cycles 5 to 22)
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-01 to 2015-06 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddEC are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m2 of epirubicin per cycle.
Preceding treatment
Chemotherapy, ddEC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddEC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, THP portion (cycles 5 to 7)
- Docetaxel (Taxotere) as follows:
- Cycle 5: 75 mg/m2 IV once on day 1
- Cycles 6 & 7: 100 mg/m2 IV once on day 1
Targeted therapy, THP portion (cycles 5 to 22)
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
Regimen variant #3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-01 to 2015-06 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddEC are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m2 of epirubicin per cycle.
Preceding treatment
Chemotherapy, ddEC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddEC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, THP portion (cycles 5 to 7)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, THP portion (cycles 5 to 22)
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
- KAITLIN: Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. link to original article dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01966471
FAC-TH (Paclitaxel)
FAC-TH: Fluorouracil, Adriamycin (Doxorubicin), Cyclophosphamide, followed by Taxol (Paclitaxel) & Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, FAC portion (cycles 1 to 3)
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 4 to 7)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 4: 8 mg/kg IV once on day 1
- Cycles 5 to 21: 6 mg/kg IV once on day 1
21-day cycle for 21 cycles (FAC x 3; TH x 4)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
FAC-TH (Docetaxel)
FAC-TH: Fluorouracil, Adriamycin (Doxorubicin), Cyclophosphamide, followed by Taxotere (Docetaxel) & Herceptin (Trastuzumab)
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, FAC portion (cycles 1 to 3)
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 4 to 7)
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 4: 8 mg/kg IV once on day 1
- Cycles 5 to 21: 6 mg/kg IV once on day 1
21-day cycle for 21 cycles (FAC x 3; TH x 4)
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, FAC portion (cycles 1 to 3)
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 4 to 6)
- Docetaxel (Taxotere) as follows:
- Cycle 4: 75 mg/m2 IV once on day 1
- Cycles 5 & 6: 100 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 4: 8 mg/kg IV once on day 1
- Cycles 5 to 21: 6 mg/kg IV once on day 1
21-day cycle for 21 cycles (FAC x 3; TH x 3)
Regimen variant #3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, FAC portion (cycles 1 to 3)
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 4 to 6)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 4: 8 mg/kg IV once on day 1
- Cycles 5 to 21: 6 mg/kg IV once on day 1
21-day cycle for 21 cycles (FAC x 3; TH x 3)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
FAC-THP (Paclitaxel)
FAC-THP: Fluorouracil, Adriamycin (Doxorubicin), Cyclophosphamide, followed by Taxol (Paclitaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, FAC portion (cycles 1 to 3)
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, THP portion (cycles 4 to 7)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, THP portion (cycles 4 to 21)
- Trastuzumab (Herceptin) as follows:
- Cycle 4: 8 mg/kg IV once on day 1
- Cycles 5 to 21: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 4: 840 mg IV once on day 1
- Cycles 5 to 21: 420 mg IV once on day 1
21-day cycle for 21 cycles (FAC x 3; THP x 4)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
FAC-THP (Docetaxel)
FAC-THP: Fluorouracil, Adriamycin (Doxorubicin), Cyclophosphamide, followed by Taxotere (Docetaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, FAC portion (cycles 1 to 3)
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, THP portion (cycles 4 to 7)
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy, THP portion (cycles 4 to 21)
- Trastuzumab (Herceptin) as follows:
- Cycle 4: 8 mg/kg IV once on day 1
- Cycles 5 to 21: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 4: 840 mg IV once on day 1
- Cycles 5 to 21: 420 mg IV once on day 1
21-day cycle for 21 cycles (FAC x 3; THP x 4)
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, FAC portion (cycles 1 to 3)
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, THP portion (cycles 4 to 6)
- Docetaxel (Taxotere) as follows:
- Cycle 4: 75 mg/m2 IV once on day 1
- Cycles 5 & 6: 100 mg/m2 IV once on day 1
Targeted therapy, THP portion (cycles 4 to 21)
- Trastuzumab (Herceptin) as follows:
- Cycle 4: 8 mg/kg IV once on day 1
- Cycles 5 to 21: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 4: 840 mg IV once on day 1
- Cycles 5 to 21: 420 mg IV once on day 1
21-day cycle for 21 cycles (FAC x 3; THP x 3)
Regimen variant #3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, FAC portion (cycles 1 to 3)
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, THP portion (cycles 4 to 6)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, THP portion (cycles 4 to 21)
- Trastuzumab (Herceptin) as follows:
- Cycle 4: 8 mg/kg IV once on day 1
- Cycles 5 to 21: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 4: 840 mg IV once on day 1
- Cycles 5 to 21: 420 mg IV once on day 1
21-day cycle for 21 cycles (FAC x 3; THP x 3)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
FEC-H
FEC-H: Fluorouracil, Epirubicin, Cyclophosphamide, followed by Herceptin (Trastuzumab)
Regimen variant #1, FEC 75
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sawaki et al. 2020 (RESPECT) | 2009-10 to 2014-11 | Randomized (C) | Trastuzumab x 1 y | Inconclusive whether non-inferior DFS (primary endpoint) |
Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Preceding treatment
Chemotherapy, FEC portion (cycles 1 to 6)
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
Targeted therapy, H portion (cycles 7 to 24)
- Trastuzumab (Herceptin) as follows:
- Cycle 7: 8 mg/kg IV once on day 1
- Cycles 8 to 24: 6 mg/kg IV once on day 1
21-day cycle for 24 cycles (FEC x 6; H x 18)
Regimen variant #2, FEC 100 x 4
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sawaki et al. 2020 (RESPECT) | 2009-10 to 2014-11 | Randomized (C) | Trastuzumab x 1 y | Inconclusive whether non-inferior DFS (primary endpoint) |
Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Preceding treatment
Chemotherapy, FEC portion (cycles 1 to 4)
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
Targeted therapy, H portion (cycles 5 to 22)
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
21-day cycle for 22 cycles (FEC x 4; H x 18)
Regimen variant #3, FEC 100 x 6
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sawaki et al. 2020 (RESPECT) | 2009-10 to 2014-11 | Randomized (C) | Trastuzumab x 1 y | Inconclusive whether non-inferior DFS (primary endpoint) |
Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Preceding treatment
Chemotherapy, FEC portion (cycles 1 to 6)
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
Targeted therapy, H portion (cycles 7 to 24)
- Trastuzumab (Herceptin) as follows:
- Cycle 7: 8 mg/kg IV once on day 1
- Cycles 8 to 24: 6 mg/kg IV once on day 1
21-day cycle for 24 cycles (FEC x 6; H x 18)
References
- RESPECT: Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. link to original article dosing details in supplement have been reviewed by our editors PubMed NCT01104935
FEC-TH (Paclitaxel)
FEC-TH: Fluorouracil, Epirubicin, Cyclophosphamide, followed by Taxol (Paclitaxel) & Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FEC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, FEC portion (cycles 1 to 3)
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 4 to 7)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 4: 8 mg/kg IV once on day 1
- Cycles 5 to 21: 6 mg/kg IV once on day 1
21-day cycle for 21 cycles (FEC x 3; TH x 4)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
FEC-TH (Docetaxel)
FEC-TH: Fluorouracil, Epirubicin, Cyclophosphamide, followed by Taxotere (Docetaxel) & Herceptin (Trastuzumab)
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FEC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, FEC portion (cycles 1 to 3)
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 4 to 7)
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 4: 8 mg/kg IV once on day 1
- Cycles 5 to 21: 6 mg/kg IV once on day 1
21-day cycle for 21 cycles (FEC x 3; TH x 4)
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FEC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, FEC portion (cycles 1 to 3)
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 4 to 6)
- Docetaxel (Taxotere) as follows:
- Cycle 4: 75 mg/m2 IV once on day 1
- Cycles 5 & 6: 100 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 4: 8 mg/kg IV once on day 1
- Cycles 5 to 21: 6 mg/kg IV once on day 1
21-day cycle for 21 cycles (FEC x 3; TH x 3)
Regimen variant #3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FEC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, FEC portion (cycles 1 to 3)
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 4 to 6)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 4: 8 mg/kg IV once on day 1
- Cycles 5 to 21: 6 mg/kg IV once on day 1
21-day cycle for 21 cycles (FEC x 3; TH x 3)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
ddFEC-ddTH (Docetaxel)
ddFEC-ddTH (Docetaxel): dose-dense Fluorouracil, Epirubicin, Cyclophosphamide, followed by ddTH: dose-dense Taxotere (Docetaxel) & Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mavroudis et al. 2015 (HORG CT/04.23) | 2004-2012 | Phase 3 (C) | ddFEC-ddTH; 6-months total of trastuzumab | Inconclusive whether non-inferior DFS36 |
Preceding treatment
Chemotherapy, ddFEC portion (cycles 1 to 4)
- Fluorouracil (5-FU) 700 mg/m2 IV over 5 to 15 minutes once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV over 5 to 15 minutes once on day 1
- Cyclophosphamide (Cytoxan) 700 mg/m2 IV over 30 to 60 minutes once on day 1
Supportive therapy, ddFEC portion (cycles 1 to 4)
- Filgrastim (Neupogen) 5 mcg/kg (rounded to 300 or 480 mcg) SC once per day on days 3 to 10
Chemotherapy, ddTH portion (cycles 5 to 20)
- Docetaxel (Taxotere) as follows:
- Cycles 5 to 8: 75 mg/m2 IV over 60 minutes once on day 1
Targeted therapy, ddTH portion (cycles 5 to 20)
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 6 mg/kg IV once on day 1
- Cycles 6 to 8: 4 mg/kg IV once on day 1
- Cycles 9 to 20: 6 mg/kg IV once on day 1
Supportive therapy, ddTH portion (cycles 5 to 20)
- Filgrastim (Neupogen) as follows:
- Cycles 5 to 8: 5 mcg/kg (rounded to 300 or 480 mcg) SC once per day on days 3 to 10
14-day cycle for 8 cycles, then 21-day cycle for 12 cycles (1 year total)
References
- HORG CT/04.23: Mavroudis D, Saloustros E, Malamos N, Kakolyris S, Boukovinas I, Papakotoulas P, Kentepozidis N, Ziras N, Georgoulias V; Hellenic Oncology Research Group. Six versus 12 months of adjuvant trastuzumab in combination with dose-dense chemotherapy for women with HER2-positive breast cancer: a multicenter randomized study by the Hellenic Oncology Research Group (HORG). Ann Oncol. 2015 Jul;26(7):1333-40. Epub 2015 May 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00615602
FEC-THP (Paclitaxel)
FEC-THP: Fluorouracil, Epirubicin, Cyclophosphamide, followed by Taxol (Paclitaxel), Herceptin (Trastuzumab), Pertuzumab
Protocol
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-01 to 2015-06 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FEC dosing and number of cycles are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m2 of epirubicin per cycle.
Preceding treatment
Chemotherapy, FEC portion
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
21-day cycle for 3 to 4 cycles
Chemotherapy, THP portion
- Paclitaxel (Taxol) as follows:
- Cycles 1 to 4: 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 18: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycles 2 to 18: 420 mg IV once on day 1
21-day cycle for 18 cycles (1 year)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
- KAITLIN: Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. link to original article dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01966471
FEC-THP (Docetaxel)
FEC-THP: Fluorouracil, Epirubicin, Cyclophosphamide, followed by Taxotere (Docetaxel), Herceptin (Trastuzumab), Pertuzumab
Protocol variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-01 to 2015-06 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FEC dosing and number of cycles are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m2 of epirubicin per cycle.
Preceding treatment
Chemotherapy, FEC portion
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
21-day cycle for 3 to 4 cycles
Chemotherapy, THP portion
- Docetaxel (Taxotere) as follows:
- Cycles 1 to 4: 75 mg/m2 IV once on day 1
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 18: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycles 2 to 18: 420 mg IV once on day 1
21-day cycle for 18 cycles (1 year)
Protocol variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-01 to 2015-06 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FEC dosing and number of cycles are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m2 of epirubicin per cycle.
Preceding treatment
Chemotherapy, FEC portion
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
21-day cycle for 3 to 4 cycles
Chemotherapy, THP portion
- Docetaxel (Taxotere) as follows:
- Cycle 1: 75 mg/m2 IV once on day 1
- Cycles 2 & 3: 100 mg/m2 IV once on day 1
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 18: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycles 2 to 18: 420 mg IV once on day 1
21-day cycle for 18 cycles (1 year)
Protocol variant #3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-01 to 2015-06 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FEC dosing and number of cycles are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m2 of epirubicin per cycle.
Preceding treatment
Chemotherapy, FEC portion
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
21-day cycle for 3 to 4 cycles
Chemotherapy, THP portion
- Docetaxel (Taxotere) as follows:
- Cycles 1 to 3: 100 mg/m2 IV once on day 1
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 18: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycles 2 to 18: 420 mg IV once on day 1
21-day cycle for 18 cycles (1 year)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
- KAITLIN: Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. link to original article dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01966471
T-H (Docetaxel)
T-H: Taxotere (Docetaxel) followed by Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sawaki et al. 2020 (RESPECT) | 2009-10 to 2014-11 | Randomized (C) | Trastuzumab x 1 y | Inconclusive whether non-inferior DFS (primary endpoint) |
Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Preceding treatment
Chemotherapy, T portion (cycles 1 to 4)
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy, H portion (cycles 5 to 22)
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
21-day cycle for 22 cycles (T x 4; H x 18)
References
- RESPECT: Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. link to original article dosing details in supplement have been reviewed by our editors PubMed NCT01104935
T-H (Paclitaxel)
T-H: Taxol (Paclitaxel) followed by Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sawaki et al. 2020 (RESPECT) | 2009-10 to 2014-11 | Randomized (C) | Trastuzumab x 1 y | Inconclusive whether non-inferior DFS (primary endpoint) |
Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Preceding treatment
Chemotherapy, T portion (cycles 1 to 12)
- Paclitaxel (Taxol) 80 mg/m2 IV once on day 1
Targeted therapy, H portion (cycles 13 to 30)
- Trastuzumab (Herceptin) as follows:
- Cycle 13: 8 mg/kg IV once on day 1
- Cycles 14 to 30: 6 mg/kg IV once on day 1
7-day cycle for 12 cycles, then 21-day cycle for 18 cycles (T x 12; H x 18)
References
- RESPECT: Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. link to original article dosing details in supplement have been reviewed by our editors PubMed NCT01104935
TC-H (Docetaxel)
TC-H: Taxotere (Docetaxel) & Cyclophosphamide, followed by Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sawaki et al. 2020 (RESPECT) | 2009-10 to 2014-11 | Randomized (C) | Trastuzumab x 1 y | Inconclusive whether non-inferior DFS (primary endpoint) |
Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Preceding treatment
Chemotherapy, TC portion (cycles 1 to 4)
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Targeted therapy, H portion (cycles 5 to 22)
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
21-day cycle for 22 cycles (TC x 4; H x 18)
References
- RESPECT: Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. link to original article dosing details in supplement have been reviewed by our editors PubMed NCT01104935
TH-FEC (Docetaxel)
TH-FEC: Taxotere (Docetaxel) & Herceptin (Trastuzumab), followed by Fluorouracil, Epirubicin, Cyclophosphamide
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Joensuu et al. 2006 (FinHer) | 2000-2003 | Phase 3 (E-esc) | 1. D-FEC 2. V-FEC |
Superior RFS (primary endpoint) Median RFS: NYR vs NYR (HR 0.42, 95% CI 0.21-0.83) |
3. VH-FEC | Not reported |
Preceding treatment
Chemotherapy, TH portion (cycles 1 to 3)
- Docetaxel (Taxotere) 100 mg/m2 IV over 60 minutes once on day 1
Targeted therapy, TH portion (cycles 1 to 3)
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 2 & 3: 2 mg/kg IV once per day on days 1, 8, 15
Chemotherapy, FEC portion (cycles 4 to 6)
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 6 cycles (TH x 3; FEC x 3)
Regimen variant #2, 600/75/600 x 3
Study | Dates of enrollment | Evidence |
---|---|---|
Joensuu et al. 2018 (SOLD) | 2008-2014 | Non-randomized part of phase 3 RCT |
Preceding treatment
Chemotherapy, TH portion (cycles 1 to 3)
- Docetaxel (Taxotere) 80 mg/m2 IV once on day 1
Targeted therapy, TH portion (cycles 1 to 3)
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 & 3: 6 mg/kg IV once on day 1
Chemotherapy, FEC portion (cycles 4 to 6)
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 6 cycles (TH x 3; FEC x 3)
Subsequent treatment
- Trastuzumab maintenance for a total of 1 year versus no further treatment
Regimen variant #3
Study | Dates of enrollment | Evidence |
---|---|---|
Joensuu et al. 2018 (SOLD) | 2008-2014 | Non-randomized part of phase 3 RCT |
Preceding treatment
Chemotherapy, TH portion (cycles 1 to 3)
- Docetaxel (Taxotere) 80 mg/m2 IV once on day 1
Targeted therapy, TH portion (cycles 1 to 3)
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 2 & 3: 2 mg/kg IV once per day on days 1, 8, 15
Chemotherapy, FEC portion (cycles 4 to 6)
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 6 cycles (TH x 3; FEC x 3)
Subsequent treatment
- Trastuzumab maintenance for a total of 1 year versus no further treatment
Regimen variant #4
Study | Dates of enrollment | Evidence |
---|---|---|
Joensuu et al. 2018 (SOLD) | 2008-2014 | Non-randomized part of phase 3 RCT |
Preceding treatment
Chemotherapy, TH portion (cycles 1 to 3)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, TH portion (cycles 1 to 3)
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 & 3: 6 mg/kg IV once on day 1
Chemotherapy, FEC portion (cycles 4 to 6)
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 6 cycles (TH x 3; FEC x 3)
Subsequent treatment
- Trastuzumab maintenance for a total of 1 year versus no further treatment
Regimen variant #5
Study | Dates of enrollment | Evidence |
---|---|---|
Joensuu et al. 2018 (SOLD) | 2008-2014 | Non-randomized part of phase 3 RCT |
Preceding treatment
Chemotherapy, TH portion (cycles 1 to 3)
- Docetaxel (Taxotere) 100 mg/m2 IV over 60 minutes once on day 1
Targeted therapy, TH portion (cycles 1 to 3)
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 2 & 3: 2 mg/kg IV once per day on days 1, 8, 15
Chemotherapy, FEC portion (cycles 4 to 6)
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 6 cycles (TH x 3; FEC x 3)
Subsequent treatment
- Trastuzumab maintenance for a total of 1 year versus no further treatment
References
- FinHer: Joensuu H, Kellokumpu-Lehtinen PL, Bono P, Alanko T, Kataja V, Asola R, Utriainen T, Kokko R, Hemminki A, Tarkkanen M, Turpeenniemi-Hujanen T, Jyrkkiö S, Flander M, Helle L, Ingalsuo S, Johansson K, Jääskeläinen AS, Pajunen M, Rauhala M, Kaleva-Kerola J, Salminen T, Leinonen M, Elomaa I, Isola J; FinHer Study Investigators. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006 Feb 23;354(8):809-20. link to original article dosing details in manuscript have been reviewed by our editors PubMed ISRCTN76560285
- Update: Joensuu H, Bono P, Kataja V, Alanko T, Kokko R, Asola R, Utriainen T, Turpeenniemi-Hujanen T, Jyrkkiö S, Möykkynen K, Helle L, Ingalsuo S, Pajunen M, Huusko M, Salminen T, Auvinen P, Leinonen H, Leinonen M, Isola J, Kellokumpu-Lehtinen PL. Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer trial. J Clin Oncol. 2009 Dec 1;27(34):5685-92. Epub 2009 Nov 2. link to original article PubMed
- SOLD: Joensuu H, Fraser J, Wildiers H, Huovinen R, Auvinen P, Utriainen M, Nyandoto P, Villman KK, Halonen P, Granstam-Björneklett H, Lundgren L, Sailas L, Turpeenniemi-Hujanen T, Tanner M, Yachnin J, Ritchie D, Johansson O, Huttunen T, Neven P, Canney P, Harvey VJ, Kellokumpu-Lehtinen PL, Lindman H. Effect of adjuvant trastuzumab for a duration of 9 weeks vs 1 year with concomitant chemotherapy for early human epidermal growth factor receptor 2-positive breast cancer: the SOLD randomized clinical trial. JAMA Oncol. 2018 Sep 1;4(9):1199-1206. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00593697
TH-FEC (Docetaxel, SC Trastuzumab)
TH-FEC: Taxotere (Docetaxel) & Herceptin Hylecta (Trastuzumab and hyaluronidase), followed by Fluorouracil, Epirubicin, Cyclophosphamide
Regimen variant #1, 80 x 3, q3wk trastuzumab
Study | Dates of enrollment | Evidence |
---|---|---|
Joensuu et al. 2018 (SOLD) | 2008-2014 | Non-randomized part of phase 3 RCT |
Preceding treatment
Chemotherapy, TH portion (cycles 1 to 3)
- Docetaxel (Taxotere) 80 mg/m2 IV once on day 1
Targeted therapy, TH portion (cycles 1 to 3)
- Trastuzumab and hyaluronidase (Herceptin Hylecta) 600 mg/10,000 units SC once on day 1
Chemotherapy, FEC portion (cycles 4 to 6)
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 6 cycles (TH x 3; FEC x 3)
Subsequent treatment
- trastuzumab maintenance for a total of 1 year versus no further treatment
Regimen variant #2, 100 x 3, q3wk trastuzumab
Study | Dates of enrollment | Evidence |
---|---|---|
Joensuu et al. 2018 (SOLD) | 2008-2014 | Non-randomized part of phase 3 RCT |
Preceding treatment
Chemotherapy, TH portion (cycles 1 to 3)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, TH portion (cycles 1 to 3)
- Trastuzumab and hyaluronidase (Herceptin Hylecta) 600 mg/10,000 units SC once on day 1
Chemotherapy, FEC portion (cycles 4 to 6)
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 6 cycles (TH x 3; FEC x 3)
Subsequent treatment
- trastuzumab maintenance for a total of 1 year versus no further treatment
References
- SOLD: Joensuu H, Fraser J, Wildiers H, Huovinen R, Auvinen P, Utriainen M, Nyandoto P, Villman KK, Halonen P, Granstam-Björneklett H, Lundgren L, Sailas L, Turpeenniemi-Hujanen T, Tanner M, Yachnin J, Ritchie D, Johansson O, Huttunen T, Neven P, Canney P, Harvey VJ, Kellokumpu-Lehtinen PL, Lindman H. Effect of adjuvant trastuzumab for a duration of 9 weeks vs 1 year with concomitant chemotherapy for early human epidermal growth factor receptor 2-positive breast cancer: the SOLD randomized clinical trial. JAMA Oncol. 2018 Sep 1;4(9):1199-1206. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00593697
VH-FEC
VH-FEC: Vinorelbine & Herceptin (Trastuzumab), followed by Fluorouracil, Epirubicin, Cyclophosphamide
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Joensuu et al. 2006 (FinHer) | 2000-2003 | Phase 3 (E-esc) | 1. D-FEC 2. V-FEC |
Superior RFS (primary endpoint) Median RFS: NYR vs NYR (HR 0.42, 95% CI 0.21-0.83) |
3. TH-FEC | Not reported |
Preceding treatment
Chemotherapy, VH portion (cycles 1 to 3)
- Vinorelbine (Navelbine) as follows:
- Cycles 1 & 2: 25 mg/m2 IV over 5 to 10 minutes once per day on days 1, 8, 15
- Cycle 3: 25 mg/m2 IV over 5 to 10 minutes once per day on days 1 & 8
Targeted therapy, VH portion (cycles 1 to 3)
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 2 & 3: 2 mg/kg IV once per day on days 1, 8, 15
Chemotherapy, FEC portion (cycles 4 to 6)
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 6 cycles (VH x 3; FEC x 3)
References
- FinHer: Joensuu H, Kellokumpu-Lehtinen PL, Bono P, Alanko T, Kataja V, Asola R, Utriainen T, Kokko R, Hemminki A, Tarkkanen M, Turpeenniemi-Hujanen T, Jyrkkiö S, Flander M, Helle L, Ingalsuo S, Johansson K, Jääskeläinen AS, Pajunen M, Rauhala M, Kaleva-Kerola J, Salminen T, Leinonen M, Elomaa I, Isola J; FinHer Study Investigators. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006 Feb 23;354(8):809-20. link to original article dosing details in manuscript have been reviewed by our editors PubMed ISRCTN76560285
- Update: Joensuu H, Bono P, Kataja V, Alanko T, Kokko R, Asola R, Utriainen T, Turpeenniemi-Hujanen T, Jyrkkiö S, Möykkynen K, Helle L, Ingalsuo S, Pajunen M, Huusko M, Salminen T, Auvinen P, Leinonen H, Leinonen M, Isola J, Kellokumpu-Lehtinen PL. Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer trial. J Clin Oncol. 2009 Dec 1;27(34):5685-92. Epub 2009 Nov 2. link to original article PubMed
Adjuvant therapy
Docetaxel & Trastuzumab (TH)
TH: Taxotere (Docetaxel) & Herceptin (Trastuzumab)
Regimen variant #1, 75 x 4, q3wk trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sawaki et al. 2020 (RESPECT) | 2009-10 to 2014-11 | Randomized (C) | Trastuzumab x 12 mo | Inconclusive whether non-inferior DFS |
Preceding treatment
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 4: 6 mg/kg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- Trastuzumab maintenance (q3wk) for a total of 1 year
Regimen variant #2, 75 x 4, weekly trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Piccart-Gebhart et al. 2015 (ALTTO) | 2007-2011 | Phase 3 (C) | 1. TH-L 2. THL (Taxotere) 3. TL (Docetaxel) |
Did not meet primary endpoint of DFS |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Surgery, then adjuvant anthracycline-based chemotherapy
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 2 to 4: 2 mg/kg IV once per day on days 1, 8, 15
21-day cycle for 4 cycles
Subsequent treatment
- Trastuzumab maintenance (q3wk) for a total of 1 year
References
- ALTTO: Piccart-Gebhart M, Holmes E, Baselga J, de Azambuja E, Dueck AC, Viale G, Zujewski JA, Goldhirsch A, Armour A, Pritchard KI, McCullough AE, Dolci S, McFadden E, Holmes AP, Tonghua L, Eidtmann H, Dinh P, Di Cosimo S, Harbeck N, Tjulandin S, Im YH, Huang CS, Diéras V, Hillman DW, Wolff AC, Jackisch C, Lang I, Untch M, Smith I, Boyle F, Xu B, Gomez H, Suter T, Gelber RD, Perez EA. Adjuvant lapatinib and trastuzumab for early human epidermal growth factor receptor 2-positive breast cancer: results from the randomized phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial. J Clin Oncol. 2016 Apr 1;34(10):1034-42. Epub 2015 Nov 23. link to original article link to protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT00490139
- Update: Moreno-Aspitia A, Holmes EM, Jackisch C, de Azambuja E, Boyle F, Hillman DW, Korde L, Fumagalli D, Izquierdo MA, McCullough AE, Wolff AC, Pritchard KI, Untch M, Guillaume S, Ewer MS, Shao Z, Sim SH, Aziz Z, Demetriou G, Mehta AO, Andersson M, Toi M, Lang I, Xu B, Smith IE, Barrios CH, Baselga J, Gelber RD, Piccart-Gebhart M; ALTTO Steering Committee and Investigators. Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D). Eur J Cancer. 2021 May;148:287-296. Epub 2021 Mar 23. link to original article link to PMC article PubMed
- RESPECT: Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01104935
CMF & H
CMF & H: Cyclophosphamide, Methotrexate, Fluorouracil, Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sawaki et al. 2020 (RESPECT) | 2009-10 to 2014-11 | Randomized (C) | Trastuzumab x 1 y | Inconclusive whether non-inferior DFS (primary endpoint) |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm. The protocol document reported a flat dose of oral cyclophosphamide, but this would not be consistent with any other known CMF variants; dosing below is provided as BSA-based.
Preceding treatment
Chemotherapy
- Cyclophosphamide (Cytoxan) as follows:
- Cycles 1 to 6: 75 to 100 mg/m2 PO once per day on days 1 to 14
- Methotrexate (MTX) as follows:
- Cycles 1 to 6: 40 mg/m2 IV once per day on days 1 & 8
- Fluorouracil (5-FU) as follows:
- Cycles 1 to 6: 500 to 600 mg/m2 IV once per day on days 1 & 8
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 18: 6 mg/kg IV once on day 1
21-day cycle for 18 cycles (1 year)
References
- RESPECT: Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. link to original article dosing details in supplement have been reviewed by our editors PubMed NCT01104935
FEC
FEC: Fluorouracil, Epirubicin, Cyclophosphamide
CEF: Cyclophosphamide, Epirubicin, Fluorouracil
Regimen variant #1, 500/100/500 x 3 ("FEC 100")
Study | Dates of enrollment | Evidence |
---|---|---|
Baselga et al. 2012 (NeoALTTO) | 2008-2010 | Non-randomized part of phase 3 RCT |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
- Lapatinib or Lapatinib & Trastuzumab or Trastuzumab maintenance, according to initial randomization
References
- NeoALTTO: Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00553358
- Update: de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. Epub 2014 Aug 14. link to original article PubMed
- Update: Huober J, Holmes E, Baselga J, de Azambuja E, Untch M, Fumagalli D, Sarp S, Lang I, Smith I, Boyle F, Xu B, Lecocq C, Wildiers H, Jouannaud C, Hackman J, Dasappa L, Ciruelos E, Toral Pena JC, Adamchuk H, Hickish T, de la Pena L, Jackisch C, Gelber RD, Piccart-Gebhart M, Di Cosimo S. Survival outcomes of the NeoALTTO study (BIG 1-06): updated results of a randomised multicenter phase III neoadjuvant clinical trial in patients with HER2-positive primary breast cancer. Eur J Cancer. 2019 Sep;118:169-177. Epub 2019 Aug 1. link to original article PubMed
- RESPECT: Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01104935
FEC & H
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Gianni et al. 2011 (NeoSphere) | 2007-2009 | Non-randomized part of phase 2 RCT |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Neoadjuvant Docetaxel & Pertuzumab versus THP (Docetaxel) versus pertuzumab & trastuzumab versus TH (Docetaxel), then surgery
Chemotherapy
- Fluorouracil (5-FU) as follows:
- Cycles 1 to 3: 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) as follows:
- Cycles 1 to 3: 90 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) as follows:
- Cycles 1 to 3: 600 mg/m2 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) 6 mg/kg IV once on day 1
21-day cycle for 18 cycles
Subsequent treatment
- NeoSphere, ER-positive patients: Radiotherapy and/or hormone therapy "per local guidelines"
References
- NeoSphere: Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, Lluch A, Staroslawska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi G, Szado T, Ratnayake J, Ross G, Valagussa P. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012 Jan;13(1):25-32. Epub 2011 Dec 6. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00545688
- Update: Gianni L, Pienkowski T, Im YH, Tseng LM, Liu MC, Lluch A, Starosławska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi GV, Magazzù D, McNally V, Douthwaite H, Ross G, Valagussa P. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 2016 Jun;17(6):791-800. Epub 2016 May 11. link to original article PubMed
Lapatinib & Trastuzumab
L+T: Lapatinib & Trastuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Piccart-Gebhart et al. 2015 (ALTTO) | 2007-2011 | Phase 3 (E-esc) | 1. Lapatinib | Did not meet primary endpoint of DFS |
2. Trastuzumab | Might have superior DFS1 (HR 0.86, 95% CI 0.74-1.00) | |||
Baselga et al. 2012 (NeoALTTO) | 2008-2010 | Phase 3 (E-esc) | See link | See link |
1Reported efficacy is based on the 2021 update.
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Targeted therapy
- Lapatinib (Tykerb) 1000 mg PO once per day
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV over 90 minutes once on day 1
- Cycles 2 to 12: 6 mg/kg IV over 30 minutes once on day 1
21-day cycle for 12 cycles (34-week course)
References
- NeoALTTO: Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00553358
- Update: de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. Epub 2014 Aug 14. link to original article PubMed
- Update: Huober J, Holmes E, Baselga J, de Azambuja E, Untch M, Fumagalli D, Sarp S, Lang I, Smith I, Boyle F, Xu B, Lecocq C, Wildiers H, Jouannaud C, Hackman J, Dasappa L, Ciruelos E, Toral Pena JC, Adamchuk H, Hickish T, de la Pena L, Jackisch C, Gelber RD, Piccart-Gebhart M, Di Cosimo S. Survival outcomes of the NeoALTTO study (BIG 1-06): updated results of a randomised multicenter phase III neoadjuvant clinical trial in patients with HER2-positive primary breast cancer. Eur J Cancer. 2019 Sep;118:169-177. Epub 2019 Aug 1. link to original article PubMed
- ALTTO: Piccart-Gebhart M, Holmes E, Baselga J, de Azambuja E, Dueck AC, Viale G, Zujewski JA, Goldhirsch A, Armour A, Pritchard KI, McCullough AE, Dolci S, McFadden E, Holmes AP, Tonghua L, Eidtmann H, Dinh P, Di Cosimo S, Harbeck N, Tjulandin S, Im YH, Huang CS, Diéras V, Hillman DW, Wolff AC, Jackisch C, Lang I, Untch M, Smith I, Boyle F, Xu B, Gomez H, Suter T, Gelber RD, Perez EA. Adjuvant lapatinib and trastuzumab for early human epidermal growth factor receptor 2-positive breast cancer: results from the randomized phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial. J Clin Oncol. 2016 Apr 1;34(10):1034-42. Epub 2015 Nov 23. link to original article link to protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT00490139
- Update: Moreno-Aspitia A, Holmes EM, Jackisch C, de Azambuja E, Boyle F, Hillman DW, Korde L, Fumagalli D, Izquierdo MA, McCullough AE, Wolff AC, Pritchard KI, Untch M, Guillaume S, Ewer MS, Shao Z, Sim SH, Aziz Z, Demetriou G, Mehta AO, Andersson M, Toi M, Lang I, Xu B, Smith IE, Barrios CH, Baselga J, Gelber RD, Piccart-Gebhart M; ALTTO Steering Committee and Investigators. Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D). Eur J Cancer. 2021 May;148:287-296. Epub 2021 Mar 23. link to original article link to PMC article PubMed
Neratinib monotherapy
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Chan et al. 2016 (ExteNET) | 2009-07-09 to 2011-10-24 | Phase 3 (E-RT-esc) | Placebo | Superior iDFS1 (primary endpoint) iDFS60: 90% vs 88% (HR 0.73, 95% CI 0.57-0.92) Did not meet secondary endpoint of OS2 OS84: 90.1% vs 90.2% (HR 0.95, 95% CI 0.75-1.21) |
1Reported efficacy is based on the 2017 update.
2Reported efficacy is based on the 2023 update.
Preceding treatment
- Surgery, then trastuzumab-containing chemotherapy or trastuzumab-containing chemotherapy, then surgery (neoadjuvant or adjuvant)
Targeted therapy
- Neratinib (Nerlynx) 240 mg PO once per day, taken with food
Supportive therapy
- (per FDA package insert)
- Loperamide (Imodium) as follows:
- Weeks 1 & 2: 4 mg PO three times per day
- Weeks 3 to 8: 4 mg PO twice per day
- Weeks 9 to 52: 4 mg PO as needed for diarrhea, not to exceed 16 mg/d
12-month course
References
- ExteNET: Chan A, Delaloge S, Holmes FA, Moy B, Iwata H, Harvey VJ, Robert NJ, Silovski T, Gokmen E, von Minckwitz G, Ejlertsen B, Chia SK, Mansi J, Barrios CH, Gnant M, Buyse M, Gore I, Smith J 2nd, Harker G, Masuda N, Petrakova K, Zotano AG, Iannotti N, Rodriguez G, Tassone P, Wong A, Bryce R, Ye Y, Yao B, Martin M; ExteNET Study Group. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2016 Mar;17(3):367-77. Epub 2016 Feb 10. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00878709
- Update: Martin M, Holmes FA, Ejlertsen B, Delaloge S, Moy B, Iwata H, von Minckwitz G, Chia SKL, Mansi J, Barrios CH, Gnant M, Tomašević Z, Denduluri N, Šeparović R, Gokmen E, Bashford A, Ruiz Borrego M, Kim SB, Jakobsen EH, Ciceniene A, Inoue K, Overkamp F, Heijns JB, Armstrong AC, Link JS, Joy AA, Bryce R, Wong A, Moran S, Yao B, Xu F, Auerbach A, Buyse M, Chan A; ExteNET Study Group. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1688-1700. Epub 2017 Nov 13. link to original article PubMed
- HRQoL analysis: Delaloge S, Cella D, Ye Y, Buyse M, Chan A, Barrios CH, Holmes FA, Mansi J, Iwata H, Ejlertsen B, Moy B, Chia SKL, Gnant M, Smichkoska S, Ciceniene A, Martinez N, Filipović S, Ben-Baruch NE, Joy AA, Langkjer ST, Senecal F, de Boer RH, Moran S, Yao B, Bryce R, Auerbach A, Fallowfield L, Martin M. Effects of neratinib on health-related quality of life in women with HER2-positive early-stage breast cancer: longitudinal analyses from the randomized phase III ExteNET trial. Ann Oncol. 2019 Apr 1;30(4):567-574. link to original article PubMed
- Subgroup analysis: Iwata H, Masuda N, Kim SB, Inoue K, Rai Y, Fujita T, Chiu J, Ohtani S, Takahashi M, Miyaki T, Lu YS, Xu B, Yap YS, Bustam A, Yao B, Zhang B, Bryce R, Chan A. Neratinib after trastuzumab-based adjuvant therapy in patients from Asia with early stage HER2-positive breast cancer. Future Oncol. 2019 Jul;15(21):2489-2501. Epub 2019 May 29. link to original article PubMed
- Subgroup analysis: Chan A, Moy B, Mansi J, Ejlertsen B, Holmes FA, Chia S, Iwata H, Gnant M, Loibl S, Barrios CH, Somali I, Smichkoska S, Martinez N, Alonso MG, Link JS, Mayer IA, Cold S, Murillo SM, Senecal F, Inoue K, Ruiz-Borrego M, Hui R, Denduluri N, Patt D, Rugo HS, Johnston SRD, Bryce R, Zhang B, Xu F, Wong A, Martin M; ExteNET Study Group. Final Efficacy Results of Neratinib in HER2-positive Hormone Receptor-positive Early-stage Breast Cancer From the Phase III ExteNET Trial. Clin Breast Cancer. 2021 Feb;21(1):80-91.e7. Epub 2020 Oct 6. link to original article PubMed
- Update: Holmes FA, Moy B, Delaloge S, Chia SKL, Ejlertsen B, Mansi J, Iwata H, Gnant M, Buyse M, Barrios CH, Silovski T, Šeparović R, Bashford A, Zotano AG, Denduluri N, Patt D, Gokmen E, Gore I, Smith JW 2nd, Loibl S, Masuda N, Tomašević Z, Petráková K, DiPrimeo D, Wong A, Martin M, Chan A; ExteNET Study Group. Overall survival with neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): A randomised, double-blind, placebo-controlled, phase 3 trial. Eur J Cancer. 2023 May;184:48-59. Epub 2023 Feb 10. link to original article PubMed
Paclitaxel & Trastuzumab (TH)
TH: Taxol (Paclitaxel) & Herceptin (Trastuzumab)
PH: Paclitaxel & Herceptin (Trastuzumab)
Regimen variant #1, weekly paclitaxel, weekly trastuzumab
Study | Dates of enrollment | Evidence |
---|---|---|
Tolaney et al. 2015 (APT) | 2007-10-29 to 2010-09-03 | Phase 2 |
Preceding treatment
Chemotherapy
- Paclitaxel (Taxol) as follows:
- Cycles 1 to 4: 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 2 to 18: 2 mg/kg IV once per day on days 1, 8, 15
21-day cycle for 18 cycles (1 year)
Regimen variant #2, weekly paclitaxel, weekly then q3wk trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tolaney et al. 2015 (APT) | 2007-10-29 to 2010-09-03 | Phase 2 | ||
Piccart-Gebhart et al. 2015 (ALTTO) | 2007-2011 | Phase 3 (C) | 1. TH-L (Paclitaxel) 2. THL (Paclitaxel) 3. TL (Paclitaxel) |
Did not meet primary endpoint of DFS |
Preceding treatment
- APT: Surgery
- ALTTO: Surgery, then adjuvant anthracycline-based chemotherapy
Chemotherapy
- Paclitaxel (Taxol) as follows:
- Cycles 1 to 4: 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 2 to 4: 2 mg/kg IV once per day on days 1, 8, 15
- Cycles 5 to 18: 6 mg/kg IV once on day 1
21-day cycle for 18 cycles (1 year)
Regimen variant #3, weekly paclitaxel, q3wk trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sawaki et al. 2020 (RESPECT) | 2009-10 to 2014-11 | Randomized (C) | Trastuzumab x 12 mo | Inconclusive whether non-inferior DFS |
Preceding treatment
Chemotherapy
- Paclitaxel (Taxol) as follows:
- Cycles 1 to 4: 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 18: 6 mg/kg IV once on day 1
21-day cycle for 18 cycles (1 year)
References
- CALGB 40101: Shulman LN, Cirrincione CT, Berry DA, Becker HP, Perez EA, O'Regan R, Martino S, Atkins JN, Mayer E, Schneider CJ, Kimmick G, Norton L, Muss H, Winer EP, Hudis C. Six Cycles of Doxorubicin and Cyclophosphamide or Paclitaxel Are Not Superior to Four Cycles As Adjuvant Chemotherapy for Breast Cancer in Women With Zero to Three Positive Axillary Nodes: Cancer and Leukemia Group B 40101. J Clin Oncol. 2012 Nov 20;30(33):4071-6. Epub 2012 Jul 23. link to original article does not contain dosing details link to study protocol PDF link to PMC article PubMed NCT00041119
- Update: Shulman LN, Berry DA, Cirrincione CT, Becker HP, Perez EA, O'Regan R, Martino S, Shapiro CL, Schneider CJ, Kimmick G, Burstein HJ, Norton L, Muss H, Hudis CA, Winer EP. Comparison of doxorubicin and cyclophosphamide versus single-agent paclitaxel as adjuvant therapy for breast cancer in women with 0 to 3 positive axillary nodes: CALGB 40101 (Alliance). J Clin Oncol. 2014 Aug 1;32(22):2311-7. Epub 2014 Jun 16. link to original article link to PMC article PubMed
- APT: Tolaney SM, Barry WT, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS, Ellis M, Shapira I, Wolff AC, Carey LA, Overmoyer BA, Partridge AH, Guo H, Hudis CA, Krop IE, Burstein HJ, Winer EP. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. N Engl J Med. 2015 Jan 8;372(2):134-41. Erratum in: N Engl J Med. 2015 Nov 12;373(20):1989. link to original article link to PMC article PubMed NCT00542451
- Update: Tolaney SM, Guo H, Pernas S, Barry WT, Dillon DA, Ritterhouse L, Schneider BP, Shen F, Fuhrman K, Baltay M, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS, Ellis MJ, Shapira I, Wolff AC, Carey LA, Overmoyer B, Partridge AH, Hudis CA, Krop IE, Burstein HJ, Winer EP. Seven-Year Follow-Up Analysis of Adjuvant Paclitaxel and Trastuzumab Trial for Node-Negative, Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer. J Clin Oncol. 2019 Aug 1;37(22):1868-1875. Epub 2019 Apr 2. link to original article link to PMC article PubMed NCT00542451
- Update: Tolaney SM, Tarantino P, Graham N, Tayob N, Parè L, Villacampa G, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS, Ellis MJ, Shapira I, Wolff AC, Carey LA, Barroso-Sousa R, Villagrasa P, DeMeo M, DiLullo M, Zanudo JGT, Weiss J, Wagle N, Partridge AH, Waks AG, Hudis CA, Krop IE, Burstein HJ, Prat A, Winer EP. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: final 10-year analysis of the open-label, single-arm, phase 2 APT trial. Lancet Oncol. 2023 Mar;24(3):273-285. link to original article PubMed
- ALTTO: Piccart-Gebhart M, Holmes E, Baselga J, de Azambuja E, Dueck AC, Viale G, Zujewski JA, Goldhirsch A, Armour A, Pritchard KI, McCullough AE, Dolci S, McFadden E, Holmes AP, Tonghua L, Eidtmann H, Dinh P, Di Cosimo S, Harbeck N, Tjulandin S, Im YH, Huang CS, Diéras V, Hillman DW, Wolff AC, Jackisch C, Lang I, Untch M, Smith I, Boyle F, Xu B, Gomez H, Suter T, Gelber RD, Perez EA. Adjuvant lapatinib and trastuzumab for early human epidermal growth factor receptor 2-positive breast cancer: results from the randomized phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial. J Clin Oncol. 2016 Apr 1;34(10):1034-42. Epub 2015 Nov 23. link to original article link to protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT00490139
- Update: Moreno-Aspitia A, Holmes EM, Jackisch C, de Azambuja E, Boyle F, Hillman DW, Korde L, Fumagalli D, Izquierdo MA, McCullough AE, Wolff AC, Pritchard KI, Untch M, Guillaume S, Ewer MS, Shao Z, Sim SH, Aziz Z, Demetriou G, Mehta AO, Andersson M, Toi M, Lang I, Xu B, Smith IE, Barrios CH, Baselga J, Gelber RD, Piccart-Gebhart M; ALTTO Steering Committee and Investigators. Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D). Eur J Cancer. 2021 May;148:287-296. Epub 2021 Mar 23. link to original article link to PMC article PubMed
- RESPECT: Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. link to original article dosing details in supplement have been reviewed by our editors PubMed NCT01104935
Pertuzumab and Trastuzumab hyaluronidase monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Tan et al. 2021 (FeDeriCa) | 2018-06-14 to 2018-12-24 | Non-randomized part of phase 3 RCT |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Neoadjuvant AC-THP (Phesgo) or ddAC-THP (Phesgo), then surgery
Targeted therapy
- Pertuzumab and Trastuzumab hyaluronidase (Phesgo) 600/600 SC once on day 1
21-day cycle for 14 cycles (42 weeks)
References
- FeDeriCa: Tan AR, Im SA, Mattar A, Colomer R, Stroyakovskii D, Nowecki Z, De Laurentiis M, Pierga JY, Jung KH, Schem C, Hogea A, Badovinac Crnjevic T, Heeson S, Shivhare M, Kirschbrown WP, Restuccia E, Jackisch C; FeDeriCa study group. Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection plus chemotherapy in HER2-positive early breast cancer (FeDeriCa): a randomised, open-label, multicentre, non-inferiority, phase 3 study. Lancet Oncol. 2021 Jan;22(1):85-97. Epub 2020 Dec 21. Erratum in: Lancet Oncol. 2021 Feb;22(2):e42. link to original article dosing details in supplement have been reviewed by our editors PubMed NCT03493854
TCH (Docetaxel)
TCH: Taxotere (Docetaxel), Carboplatin, Herceptin (Trastuzumab)
TCbH: Taxotere (Docetaxel), Carboplatin, Herceptin (Trastuzumab)
Regimen variant #1, 60/5
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sawaki et al. 2020 (RESPECT) | 2009-10 to 2014-11 | Randomized (C) | Trastuzumab x 1 y | Inconclusive whether non-inferior DFS (primary endpoint) |
Note: This was suggested as an "acceptable" dose for elderly patients, given immature safety results of BCIRG 006.
Preceding treatment
Chemotherapy
- Docetaxel (Taxotere) as follows:
- Cycles 1 to 6: 60 mg/m2 IV once on day 1
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6: AUC 5 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 2 to 6: 2 mg/kg IV once per day on days 1, 8, 15
- Cycles 7 to 18: 6 mg/kg IV once on day 1
21-day cycle for 18 cycles (1 year)
Regimen variant #2, 75/6, capped carboplatin
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy is based on the 2021 update.
Preceding treatment
Chemotherapy
- Docetaxel (Taxotere) as follows:
- Cycles 1 to 6: 75 mg/m2 IV once on day 1
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6: AUC 6 (maximum dose of 900 mg) IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 18: 6 mg/kg IV once on day 1
21-day cycle for up to 18 cycles (1 year)
Regimen variant #3, 75/6, no cap
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Slamon et al. 2011 (BCIRG 006) | 2001-2004 | Phase 3 (E-RT-esc) | 1. AC-D | Seems to have superior OS (secondary endpoint) |
2. AC-TH | Did not meet primary endpoint of DFS | |||
Piccart-Gebhart et al. 2015 (ALTTO) | 2007-2011 | Phase 3 (C) | 1. TCL 2. TCH-L 3. TCHL |
Did not meet primary endpoint of DFS |
Sawaki et al. 2020 (RESPECT) | 2009-10 to 2014-11 | Randomized (C) | Trastuzumab x 1 y | Inconclusive whether non-inferior DFS (primary endpoint) |
Preceding treatment
Chemotherapy
- Docetaxel (Taxotere) as follows:
- Cycles 1 to 6: 75 mg/m2 IV once on day 1
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6: AUC 6 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 2 to 6: 2 mg/kg IV once per day on days 1, 8, 15
- Cycles 7 to 18: 6 mg/kg IV once on day 1
Supportive therapy
- ALTTO: G-CSF use is mandatory (details not provided)
21-day cycle for 18 cycles (1 year)
References
- BCIRG 006: Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J; Breast Cancer International Research Group. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011 Oct 6;365(14):1273-83. link to original article link to PMC article PubMed NCT00021255
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
- ALTTO: Piccart-Gebhart M, Holmes E, Baselga J, de Azambuja E, Dueck AC, Viale G, Zujewski JA, Goldhirsch A, Armour A, Pritchard KI, McCullough AE, Dolci S, McFadden E, Holmes AP, Tonghua L, Eidtmann H, Dinh P, Di Cosimo S, Harbeck N, Tjulandin S, Im YH, Huang CS, Diéras V, Hillman DW, Wolff AC, Jackisch C, Lang I, Untch M, Smith I, Boyle F, Xu B, Gomez H, Suter T, Gelber RD, Perez EA. Adjuvant lapatinib and trastuzumab for early human epidermal growth factor receptor 2-positive breast cancer: results from the randomized phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial. J Clin Oncol. 2016 Apr 1;34(10):1034-42. Epub 2015 Nov 23. link to original article link to protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT00490139
- Update: Moreno-Aspitia A, Holmes EM, Jackisch C, de Azambuja E, Boyle F, Hillman DW, Korde L, Fumagalli D, Izquierdo MA, McCullough AE, Wolff AC, Pritchard KI, Untch M, Guillaume S, Ewer MS, Shao Z, Sim SH, Aziz Z, Demetriou G, Mehta AO, Andersson M, Toi M, Lang I, Xu B, Smith IE, Barrios CH, Baselga J, Gelber RD, Piccart-Gebhart M; ALTTO Steering Committee and Investigators. Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D). Eur J Cancer. 2021 May;148:287-296. Epub 2021 Mar 23. link to original article link to PMC article PubMed
- RESPECT: Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01104935
TCHP (Docetaxel)
TCHP: Taxotere (Docetaxel), Carboplatin, Herceptin (Trastuzumab), Pertuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-RT-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
1Reported efficacy is based on the 2021 update.
Preceding treatment
Chemotherapy
- Docetaxel (Taxotere) as follows:
- Cycles 1 to 6: 75 mg/m2 IV once on day 1
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6: AUC 6 (maximum dose: 900 mg) IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 18: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycles 2 to 18: 420 mg IV once on day 1
21-day cycle for up to 18 cycles (1 year)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
TCyH (Docetaxel)
TCyH: Taxotere (Docetaxel), Cyclophosphamide, Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Jones et al. 2013 (US Oncology 06-038) | 2007-2009 | Phase 2 |
Preceding treatment
- Surgery, within 84 days
Chemotherapy
- Docetaxel (Taxotere) as follows:
- Cycles 1 to 4: 75 mg/m2 IV over 60 minutes once on day 1
- Cyclophosphamide (Cytoxan) as follows:
- Cycles 1 to 4: 600 mg/m2 IV over 15 to 30 minutes once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV over 90 minutes once on day 1, then 2 mg/kg IV over 30 to 60 minutes once per day on days 8 & 15
- Cycles 2 to 4: 2 mg/kg IV over 30 to 60 minutes once per day on days 1, 8, 15
- Cycles 6 to 18: 6 mg/kg IV once on day 1
Supportive therapy
- Use of Filgrastim (Neupogen) or Pegfilgrastim (Neulasta) was allowed.
- Prophylactic antibiotics were not recommended.
21-day cycle for 18 cycles
References
- US Oncology 06-038: Jones SE, Collea R, Paul D, Sedlacek S, Favret AM, Gore I Jr, Lindquist DL, Holmes FA, Allison MA, Brooks BD, Portillo RM, Vukelja SJ, Steinberg MS, Stokoe C, Crockett MW, Wang Y, Asmar L, Robert NJ, O'Shaughnessy J. Adjuvant docetaxel and cyclophosphamide plus trastuzumab in patients with HER2-amplified early stage breast cancer: a single-group, open-label, phase 2 study. Lancet Oncol. 2013 Oct;14(11):1121-8. Epub 2013 Sep 2. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00493649
- RESPECT: Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01104935
Trastuzumab monotherapy
Regimen variant #1, 6 mo course
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Earl et al. 2019 (PERSEPHONE) | 2007-2015 | Phase 3 (E-de-esc) | Trastuzumab x 12 mo | Non-inferior DFS (primary endpoint) DFS48: 89.4% vs 89.8% (HR 1.07, 90% CI 0.93-1.24) |
Preceding treatment
- Not explicitly specified (pragmatic trial)
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV over 90 minutes once on day 1
- Cycles 2 onwards: 6 mg/kg IV over 90 minutes once on day 1
21-day cycle for 9 cycles (6 months)
Regimen variant #2, 30-week course, q3wk
Study | Dates of enrollment | Evidence |
---|---|---|
Pivot et al. 2018 (SB3-G31-BC) | 2014-04 to 2015-08 | Non-randomized part of phase 3 RCT |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Neoadjuvant TH-FEC & H, then surgery
Targeted therapy
- Trastuzumab (Herceptin) 6 mg/kg IV over 30 minutes once on day 1
21-day cycle for 10 cycles (30-week course)
Regimen variant #3, 34-week course, q3wk
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Baselga et al. 2012 (NeoALTTO) | 2008-2010 | Phase 3 (C) | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV over 90 minutes once on day 1
- Cycles 2 to 12: 6 mg/kg IV over 30 minutes once on day 1
21-day cycle for 12 cycles (34-week course)
Regimen variant #4, 42-week course, q3wk
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2018 (KATHERINE) | 2013-2015 | Phase 3 (C) | T-DM1 | Inferior IDFS |
Note: the loading dose in cycle 1 was only used if it had been more than 6 weeks since any preceding dose of trastuzumab.
Preceding treatment
- Surgery, with residual invasive disease
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 14: 6 mg/kg IV once on day 1
21-day cycle for 14 cycles
Regimen variant #5, 1-year total course, q3wk
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Piccart-Gebhart et al. 2005 (HERA) | 2001-2005 | Phase 3 (E-RT-esc) | 1. No trastuzumab after (neo-)adjuvant chemotherapy | Superior OS1 (secondary endpoint) OS144: 79% vs 73% (HR 0.74, 95% CI 0.64-0.86) |
2. Trastuzumab x 2 y | Did not meet primary endpoint of DFS | |||
Gianni et al. 2010 (NOAH) | 2002-2005 | Phase 3 (E-esc) | See link | See link |
Pivot et al. 2013 (PHARE) | 2006-2010 | Phase 3 (C) | Trastuzumab x 6 mo | Inconclusive whether non-inferior DFS |
Piccart-Gebhart et al. 2015 (ALTTO) | 2007-2011 | Phase 3 (C) | 1. Lapatinib 2. T-L |
Did not meet primary endpoint of DFS |
3. Lapatinib & Trastuzumab | Might have inferior DFS2 | |||
Earl et al. 2019 (PERSEPHONE) | 2007-2015 | Phase 3 (C) | Trastuzumab x 6 mo | Non-inferior DFS |
Conte et al. 2018 (Short-HER) | 2007 to not reported | Phase 3 (C) | Trastuzumab x 9 wks | Inconclusive whether non-inferior DFS |
Joensuu et al. 2018 (SOLD) | 2008-2014 | Phase 3 (C) | No further treatment | Inconclusive whether non-inferior DFS |
Sawaki et al. 2020 (RESPECT) | 2009-10 to 2014-11 | Randomized (E-de-esc) | 1a. AC-H 1b. CMF & H 1c. CMF-H 1d. EC-H 1e. FEC-H 1f. T-H (Paclitaxel) 1g. T-H (Docetaxel) 1h. TC-H 1i. TCH 1j. TH (Paclitaxel) 1k. TH (Docetaxel) |
Inconclusive whether non-inferior DFS (primary endpoint) |
1Reported efficacy for HERA is based on the 2017 update.
2Reported efficacy for ALTTO is based on the 2021 update.
Note: for patients already receiving trastuzumab prior to transitioning to monotherapy, re-loading is not necessary.
Preceding treatment
- HERA: surgery, then at least four cycles of an approved adjuvant chemotherapy regimen or at least four cycles of an approved neoadjuvant chemotherapy regimen, then surgery
- PERSEPHONE: Not explicitly specified (pragmatic trial)
- SOLD: Surgery, then adjuvant TH-FEC or TH-FEC (SC)
- Short-HER: Surgery, then adjuvant AC x 4 or EC x 4, then adjuvant TH (Paclitaxel) or TH (Docetaxel)
- RESPECT: Surgery
Targeted therapy
- Trastuzumab (Herceptin) as follows (see note):
- Cycle 1: 8 mg/kg IV over 90 minutes once on day 1
- Cycles 2 to 18: 6 mg/kg IV over 90 minutes once on day 1
21-day cycle for 18 cycles (1 year)
Regimen variant #6, 2-year course
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Piccart-Gebhart et al. 2005 (HERA) | 2001-2005 | Phase 3 (E-RT-esc) | 1. No trastuzumab after (neo-)adjuvant chemotherapy | Not reported |
2. Trastuzumab x 1 y | Did not meet primary endpoint of DFS |
Preceding treatment
- HERA: surgery, then at least four cycles of an approved adjuvant chemotherapy regimen or at least four cycles of an approved neoadjuvant chemotherapy regimen, then surgery
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV over 90 minutes once on day 1
- Cycles 2 to 35: 6 mg/kg IV over 90 minutes once on day 1
21-day cycle for 35 cycles (2 years)
References
- HERA: Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C, Cameron D, Dowsett M, Barrios CH, Steger G, Huang CS, Andersson M, Inbar M, Lichinitser M, Láng I, Nitz U, Iwata H, Thomssen C, Lohrisch C, Suter TM, Rüschoff J, Suto T, Greatorex V, Ward C, Straehle C, McFadden E, Dolci MS, Gelber RD; Herceptin Adjuvant (HERA) Trial Study Team. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1659-72. link to original article dosing details in manuscript have been reviewed by our editors link to data supplement PubMed NCT00045032
- Update: Smith I, Procter M, Gelber RD, Guillaume S, Feyereislova A, Dowsett M, Goldhirsch A, Untch M, Mariani G, Baselga J, Kaufmann M, Cameron D, Bell R, Bergh J, Coleman R, Wardley A, Harbeck N, Lopez RI, Mallmann P, Gelmon K, Wilcken N, Wist E, Sánchez Rovira P, Piccart-Gebhart MJ; HERA study team. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet. 2007 Jan 6;369(9555):29-36. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Update: Gianni L, Dafni U, Gelber RD, Azambuja E, Muehlbauer S, Goldhirsch A, Untch M, Smith I, Baselga J, Jackisch C, Cameron D, Mano M, Pedrini JL, Veronesi A, Mendiola C, Pluzanska A, Semiglazov V, Vrdoljak E, Eckart MJ, Shen Z, Skiadopoulos G, Procter M, Pritchard KI, Piccart-Gebhart MJ, Bell R; Herceptin Adjuvant (HERA) Trial Study Team. Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncol. 2011 Mar;12(3):236-44. Epub 2011 Feb 25. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Update: Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, de Azambuja E, Procter M, Suter TM, Jackisch C, Cameron D, Weber HA, Heinzmann D, Dal Lago L, McFadden E, Dowsett M, Untch M, Gianni L, Bell R, Köhne CH, Vindevoghel A, Andersson M, Brunt AM, Otero-Reyes D, Song S, Smith I, Leyland-Jones B, Baselga J; Herceptin Adjuvant (HERA) Trial Study Team. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet. 2013 Sep 21;382(9897):1021-8. Epub 2013 Jul 18. link to original article PubMed
- Update: Cameron D, Piccart-Gebhart MJ, Gelber RD, Procter M, Goldhirsch A, de Azambuja E, Castro G Jr, Untch M, Smith I, Gianni L, Baselga J, Al-Sakaff N, Lauer S, McFadden E, Leyland-Jones B, Bell R, Dowsett M, Jackisch C; Herceptin Adjuvant (HERA) Trial Study Team. 11 years' follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017 Mar 25;389(10075):1195-1205. Epub 2017 Feb 17. link to original article link to PMC article PubMed
- NOAH: Gianni L, Eiermann W, Semiglazov V, Manikhas A, Lluch A, Tjulandin S, Zambetti M, Vazquez F, Byakhow M, Lichinitser M, Climent MA, Ciruelos E, Ojeda B, Mansutti M, Bozhok A, Baronio R, Feyereislova A, Barton C, Valagussa P, Baselga J. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet. 2010 Jan 30;375(9712):377-84. link to original article dosing details in manuscript have been reviewed by our editors PubMed ISRCTN86043495
- Update: Gianni L, Eiermann W, Semiglazov V, Lluch A, Tjulandin S, Zambetti M, Moliterni A, Vazquez F, Byakhov MJ, Lichinitser M, Climent MA, Ciruelos E, Ojeda B, Mansutti M, Bozhok A, Magazzù D, Heinzmann D, Steinseifer J, Valagussa P, Baselga J. Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH): follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet Oncol. 2014 May;15(6):640-7. Epub 2014 Mar 20. Erratum in: Lancet Oncol. 2018 Dec;19(12):e667. link to original article PubMed
- NeoALTTO: Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00553358
- Update: de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. Epub 2014 Aug 14. link to original article PubMed
- Update: Huober J, Holmes E, Baselga J, de Azambuja E, Untch M, Fumagalli D, Sarp S, Lang I, Smith I, Boyle F, Xu B, Lecocq C, Wildiers H, Jouannaud C, Hackman J, Dasappa L, Ciruelos E, Toral Pena JC, Adamchuk H, Hickish T, de la Pena L, Jackisch C, Gelber RD, Piccart-Gebhart M, Di Cosimo S. Survival outcomes of the NeoALTTO study (BIG 1-06): updated results of a randomised multicenter phase III neoadjuvant clinical trial in patients with HER2-positive primary breast cancer. Eur J Cancer. 2019 Sep;118:169-177. Epub 2019 Aug 1. link to original article PubMed
- CALGB 40101: Shulman LN, Cirrincione CT, Berry DA, Becker HP, Perez EA, O'Regan R, Martino S, Atkins JN, Mayer E, Schneider CJ, Kimmick G, Norton L, Muss H, Winer EP, Hudis C. Six Cycles of Doxorubicin and Cyclophosphamide or Paclitaxel Are Not Superior to Four Cycles As Adjuvant Chemotherapy for Breast Cancer in Women With Zero to Three Positive Axillary Nodes: Cancer and Leukemia Group B 40101. J Clin Oncol. 2012 Nov 20;30(33):4071-6. Epub 2012 Jul 23. link to original article dosing details in manuscript have been reviewed by our editors link to study protocol PDF link to PMC article PubMed NCT00041119
- Update: Shulman LN, Berry DA, Cirrincione CT, Becker HP, Perez EA, O'Regan R, Martino S, Shapiro CL, Schneider CJ, Kimmick G, Burstein HJ, Norton L, Muss H, Hudis CA, Winer EP. Comparison of doxorubicin and cyclophosphamide versus single-agent paclitaxel as adjuvant therapy for breast cancer in women with 0 to 3 positive axillary nodes: CALGB 40101 (Alliance). J Clin Oncol. 2014 Aug 1;32(22):2311-7. Epub 2014 Jun 16. link to original article link to PMC article PubMed
- PHARE: Pivot X, Romieu G, Debled M, Pierga JY, Kerbrat P, Bachelot T, Lortholary A, Espié M, Fumoleau P, Serin D, Jacquin JP, Jouannaud C, Rios M, Abadie-Lacourtoisie S, Tubiana-Mathieu N, Cany L, Catala S, Khayat D, Pauporté I, Kramar A; PHARE trial investigators. 6 months versus 12 months of adjuvant trastuzumab for patients with HER2-positive early breast cancer (PHARE): a randomised phase 3 trial. Lancet Oncol. 2013 Jul;14(8):741-8. Epub 2013 Jun 11. link to original article PubMed NCT00381901
- Update: Pivot X, Romieu G, Debled M, Pierga JY, Kerbrat P, Bachelot T, Lortholary A, Espié M, Fumoleau P, Serin D, Jacquin JP, Jouannaud C, Rios M, Abadie-Lacourtoisie S, Venat-Bouvet L, Cany L, Catala S, Khayat D, Gambotti L, Pauporté I, Faure-Mercier C, Paget-Bailly S, Henriques J, Grouin JM; PHARE trial investigators. 6 months versus 12 months of adjuvant trastuzumab in early breast cancer (PHARE): final analysis of a multicentre, open-label, phase 3 randomised trial. Lancet. 2019 Jun 29;393(10191):2591-2598. Epub 2019 Jun 6. link to original article PubMed
- ALTTO: Piccart-Gebhart M, Holmes E, Baselga J, de Azambuja E, Dueck AC, Viale G, Zujewski JA, Goldhirsch A, Armour A, Pritchard KI, McCullough AE, Dolci S, McFadden E, Holmes AP, Tonghua L, Eidtmann H, Dinh P, Di Cosimo S, Harbeck N, Tjulandin S, Im YH, Huang CS, Diéras V, Hillman DW, Wolff AC, Jackisch C, Lang I, Untch M, Smith I, Boyle F, Xu B, Gomez H, Suter T, Gelber RD, Perez EA. Adjuvant lapatinib and trastuzumab for early human epidermal growth factor receptor 2-positive breast cancer: results from the randomized phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial. J Clin Oncol. 2016 Apr 1;34(10):1034-42. Epub 2015 Nov 23. link to original article link to protocol dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT00490139
- Update: Moreno-Aspitia A, Holmes EM, Jackisch C, de Azambuja E, Boyle F, Hillman DW, Korde L, Fumagalli D, Izquierdo MA, McCullough AE, Wolff AC, Pritchard KI, Untch M, Guillaume S, Ewer MS, Shao Z, Sim SH, Aziz Z, Demetriou G, Mehta AO, Andersson M, Toi M, Lang I, Xu B, Smith IE, Barrios CH, Baselga J, Gelber RD, Piccart-Gebhart M; ALTTO Steering Committee and Investigators. Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D). Eur J Cancer. 2021 May;148:287-296. Epub 2021 Mar 23. link to original article link to PMC article PubMed
- SB3-G31-BC: Pivot X, Bondarenko I, Nowecki Z, Dvorkin M, Trishkina E, Ahn JH, Vinnyk Y, Im SA, Sarosiek T, Chatterjee S, Wojtukiewicz MZ, Moiseyenko V, Shparyk Y, Bello M 3rd, Semiglazov V, Song S, Lim J. Phase III, randomized, double-blind study comparing the efficacy, safety, and immunogenicity of SB3 (trastuzumab biosimilar) and reference trastuzumab in patients treated with neoadjuvant therapy for human epidermal growth factor receptor 2-positive early breast cancer. J Clin Oncol. 2018 Apr 1;36(10):968-974. Epub 2018 Jan 26. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02149524
- SOLD: Joensuu H, Fraser J, Wildiers H, Huovinen R, Auvinen P, Utriainen M, Nyandoto P, Villman KK, Halonen P, Granstam-Björneklett H, Lundgren L, Sailas L, Turpeenniemi-Hujanen T, Tanner M, Yachnin J, Ritchie D, Johansson O, Huttunen T, Neven P, Canney P, Harvey VJ, Kellokumpu-Lehtinen PL, Lindman H. Effect of adjuvant trastuzumab for a duration of 9 weeks vs 1 year with concomitant chemotherapy for early human epidermal growth factor receptor 2-positive breast cancer: the SOLD randomized clinical trial. JAMA Oncol. 2018 Sep 1;4(9):1199-1206. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00593697
- Short-HER: Conte P, Frassoldati A, Bisagni G, Brandes AA, Donadio M, Garrone O, Piacentini F, Cavanna L, Giotta F, Aieta M, Gebbia V, Molino A, Musolino A, Ferro A, Maltoni R, Danese S, Zamagni C, Rimanti A, Cagossi K, Russo A, Pronzato P, Giovanardi F, Moretti G, Lombardo L, Schirone A, Beano A, Amaducci L, Bajardi EA, Vicini R, Balduzzi S, D'Amico R, Guarneri V; Reader study level-I and level-II Groups. Nine weeks versus 1 year adjuvant trastuzumab in combination with chemotherapy: final results of the phase III randomized Short-HER study. Ann Oncol. 2018 Dec 1;29(12):2328-2333. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00629278
- Update: Conte P, Bisagni G, Piacentini F, Sarti S, Minichillo S, Anselmi E, Aieta M, Gebbia V, Schirone A, Musolino A, Garrone O, Beano A, Rimanti A, Giotta F, Turletti A, Miglietta F, Dieci MV, Vicini R, Balduzzi S, D'Amico R, Guarneri V. Nine-Week Versus One-Year Trastuzumab for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: 10-Year Update of the ShortHER Phase III Randomized Trial. J Clin Oncol. 2023 Nov 10;41(32):4976-4981. Epub 2023 Sep 25. link to original article link to PMC article PubMed
- KATHERINE: von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M, Wolmark N, Rastogi P, Schneeweiss A, Redondo A, Fischer HH, Jacot W, Conlin AK, Arce-Salinas C, Wapnir IL, Jackisch C, DiGiovanna MP, Fasching PA, Crown JP, Wülfing P, Shao Z, Rota Caremoli E, Wu H, Lam LH, Tesarowski D, Smitt M, Douthwaite H, Singel SM, Geyer CE Jr; KATHERINE Investigators. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med. 2019 Feb 14;380(7):617-628. Epub 2018 Dec 5. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01772472
- PERSEPHONE: Earl HM, Hiller L, Vallier AL, Loi S, McAdam K, Hughes-Davies L, Harnett AN, Ah-See ML, Simcock R, Rea D, Raj S, Woodings P, Harries M, Howe D, Raynes K, Higgins HB, Wilcox M, Plummer C, Mansi J, Gounaris I, Mahler-Araujo B, Provenzano E, Chhabra A, Abraham JE, Caldas C, Hall PS, McCabe C, Hulme C, Miles D, Wardley AM, Cameron DA, Dunn JA; PERSEPHONE Steering Committee and Trial Investigators. 6 versus 12 months of adjuvant trastuzumab for HER2-positive early breast cancer (PERSEPHONE): 4-year disease-free survival results of a randomised phase 3 non-inferiority trial. Lancet. 2019 Jun 29;393(10191):2599-2612. Epub 2019 Jun 6. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00712140
- RESPECT: Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01104935
Trastuzumab and hyaluronidase monotherapy
Regimen variant #1, 6 mos
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Earl et al. 2019 (PERSEPHONE) | 2007-2015 | Phase 3 (E-de-esc) | Trastuzumab x 12 mo | Non-inferior DFS (primary endpoint) DFS48: 89.4% vs 89.8% (HR 1.07, 90% CI 0.93-1.24) |
Preceding treatment
- Not explicitly specified (pragmatic trial)
Targeted therapy
- Trastuzumab and hyaluronidase (Herceptin Hylecta) 600 mg/10,000 units SC once on day 1
21-day cycle for 9 cycles (6 months)
Regimen variant #2, 12 mos
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Earl et al. 2019 (PERSEPHONE) | 2007-2015 | Phase 3 (C) | Trastuzumab x 6 mo | Non-inferior DFS |
Joensuu et al. 2018 (SOLD) | 2008-2014 | Phase 3 (C) | No further treatment | Inconclusive whether non-inferior DFS |
Preceding treatment
- SOLD: Surgery, then adjuvant TH-FEC or TH-FEC (SC)
- PERSEPHONE: Not explicitly specified (pragmatic trial)
Targeted therapy
- Trastuzumab and hyaluronidase (Herceptin Hylecta) 600 mg/10,000 units SC once on day 1
21-day cycle for 18 cycles (1 year)
References
- SOLD: Joensuu H, Fraser J, Wildiers H, Huovinen R, Auvinen P, Utriainen M, Nyandoto P, Villman KK, Halonen P, Granstam-Björneklett H, Lundgren L, Sailas L, Turpeenniemi-Hujanen T, Tanner M, Yachnin J, Ritchie D, Johansson O, Huttunen T, Neven P, Canney P, Harvey VJ, Kellokumpu-Lehtinen PL, Lindman H. Effect of adjuvant trastuzumab for a duration of 9 weeks vs 1 year with concomitant chemotherapy for early human epidermal growth factor receptor 2-positive breast cancer: the SOLD randomized clinical trial. JAMA Oncol. 2018 Sep 1;4(9):1199-1206. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00593697
- PERSEPHONE: Earl HM, Hiller L, Vallier AL, Loi S, McAdam K, Hughes-Davies L, Harnett AN, Ah-See ML, Simcock R, Rea D, Raj S, Woodings P, Harries M, Howe D, Raynes K, Higgins HB, Wilcox M, Plummer C, Mansi J, Gounaris I, Mahler-Araujo B, Provenzano E, Chhabra A, Abraham JE, Caldas C, Hall PS, McCabe C, Hulme C, Miles D, Wardley AM, Cameron DA, Dunn JA; PERSEPHONE Steering Committee and Trial Investigators. 6 versus 12 months of adjuvant trastuzumab for HER2-positive early breast cancer (PERSEPHONE): 4-year disease-free survival results of a randomised phase 3 non-inferiority trial. Lancet. 2019 Jun 29;393(10191):2599-2612. Epub 2019 Jun 6. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00712140
Trastuzumab emtansine monotherapy
T-DM1: Trastuzumab-DM1 (Trastuzumab emtansine)
Example orders
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2018 (KATHERINE) | 2013-2015 | Phase 3 (E-RT-switch-ic) | Trastuzumab | Superior IDFS (primary endpoint) IDFS36: 88% vs 77% (HR 0.50, 95% CI 0.39-0.64) |
Preceding treatment
- Surgery, with residual invasive disease
Antibody-drug conjugate therapy
- Trastuzumab emtansine (Kadcyla) 3.6 mg/kg IV once on day 1
21-day cycle for 14 cycles
References
- KATHERINE: von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M, Wolmark N, Rastogi P, Schneeweiss A, Redondo A, Fischer HH, Jacot W, Conlin AK, Arce-Salinas C, Wapnir IL, Jackisch C, DiGiovanna MP, Fasching PA, Crown JP, Wülfing P, Shao Z, Rota Caremoli E, Wu H, Lam LH, Tesarowski D, Smitt M, Douthwaite H, Singel SM, Geyer CE Jr; KATHERINE Investigators. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med. 2019 Feb 14;380(7):617-628. Epub 2018 Dec 5. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01772472
- CompassHER2 RD: NCT04457596
Metastatic or unresectable disease, first-line
Note: some patients in these trials were pre-treated with non-HER2-targeted therapies.
ACH
ACH: Adriamycin (Doxorubicin), Cyclophosphamide, Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Slamon et al. 2001 | 1995-1997 | Phase 3 (E-RT-esc) | 1a. AC 1b. EC |
Seems to have superior OS (secondary endpoint) Median OS: 25.1 vs 20.3 mo Superior TTP (co-primary endpoint) Median TTP: 7.4 vs 4.6 mo |
Note: This is not commonly used; here for reference purposes only.
Prior treatment criteria
- Slamon et al. 2001: No previous anthracycline exposure
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/mg2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/mg2 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycle 2 onwards: 2 mg/kg IV once per day on days 1, 8, 15
21-day cycles
References
- Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001 Mar 15;344(11):783-92. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Capecitabine, Bevacizumab, Trastuzumab
Regimen
Study | Dates of enrollment | Evidence | Efficacy |
---|---|---|---|
Martín et al. 2012 (MO21926) | 2008-2010 | Phase 2 | ORR: 73% (95% CI 62-82) |
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
Targeted therapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
References
- MO21926: Martín M, Makhson A, Gligorov J, Lichinitser M, Lluch A, Semiglazov V, Scotto N, Mitchell L, Tjulandin S. Phase II study of bevacizumab in combination with trastuzumab and capecitabine as first-line treatment for HER-2-positive locally recurrent or metastatic breast cancer. Oncologist. 2012;17(4):469-75. Epub 2012 Mar 30. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00811135
Capecitabine & Lapatinib
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pivot et al. 2015 (CEREBEL) | 2009-2012 | Phase 3 (E-switch-ic) | Capecitabine & Trastuzumab | Did not meet primary endpoint of CNS metastases as first site of relapse |
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
Targeted therapy
- Lapatinib (Tykerb) 1250 mg PO once per day on days 1 to 21
21-day cycles
References
- CEREBEL: Pivot X, Manikhas A, Żurawski B, Chmielowska E, Karaszewska B, Allerton R, Chan S, Fabi A, Bidoli P, Gori S, Ciruelos E, Dank M, Hornyak L, Margolin S, Nusch A, Parikh R, Nagi F, DeSilvio M, Santillana S, Swaby RF, Semiglazov V. CEREBEL (EGF111438): A phase III, randomized, open-label study of lapatinib plus capecitabine versus trastuzumab plus capecitabine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2015 May 10;33(14):1564-73. Epub 2015 Jan 20. link to original article PubMed NCT00820222
Capecitabine & Trastuzumab (XH)
XH: Xeloda (Capecitabine) & Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pivot et al. 2015 (CEREBEL) | 2009-2012 | Phase 3 (C) | Capecitabine & Lapatanib | Did not meet primary endpoint of CNS metastases as first site of relapse |
Chemotherapy
- Capecitabine (Xeloda) 1250 mg/m2 PO twice per day on days 1 to 14
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
References
- CEREBEL: Pivot X, Manikhas A, Żurawski B, Chmielowska E, Karaszewska B, Allerton R, Chan S, Fabi A, Bidoli P, Gori S, Ciruelos E, Dank M, Hornyak L, Margolin S, Nusch A, Parikh R, Nagi F, DeSilvio M, Santillana S, Swaby RF, Semiglazov V. CEREBEL (EGF111438): A phase III, randomized, open-label study of lapatinib plus capecitabine versus trastuzumab plus capecitabine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2015 May 10;33(14):1564-73. Epub 2015 Jan 20. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00820222
Carboplatin & Paclitaxel (CP) & Trastuzumab
TPC: Trastuzumab, Paclitaxel, Carboplatin
TCH: Taxol (Paclitaxel), Carboplatin, Herceptin (Trastuzumab)
Regimen variant #1, weekly
Study | Dates of enrollment | Evidence |
---|---|---|
Perez et al. 2005 (NCCTG 983252) | 1999-04 to 2003-07 | Phase 2 |
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22
- Cycles 2 to 6: 2 mg/kg IV once per day on days 1, 8, 15, 22
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
- Carboplatin (Paraplatin) AUC 2 IV once per day on days 1, 8, 15
28-day cycle for 6 cycles
Subsequent treatment
- Trastuzumab maintenance (weekly)
Regimen variant #2, weekly T, q3wk PC
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Robert et al. 2006 | 1998-2002 | Phase 3 (E-esc) | TP | Superior PFS (secondary endpoint) Median PFS: 10.7 vs 7.1 mo (HR 0.66, 95% CI 0.59-0.73) Seems to have superior ORR (primary endpoint) |
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycle 2 onwards: 2 mg/kg IV once per day on days 1, 8, 15
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 2
- Carboplatin (Paraplatin) AUC 6 IV once on day 2
21-day cycle for at least 6 cycles
Subsequent treatment
- Trastuzumab maintenance (weekly)
Regimen variant #3, q3wk
Study | Dates of enrollment | Evidence |
---|---|---|
Perez et al. 2005 (NCCTG 983252) | 1999-04 to 2003-07 | Phase 2 |
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 8: 6 mg/kg IV once on day 1
Chemotherapy
- Paclitaxel (Taxol) 200 mg/m2 IV once on day 1
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
21-day cycle for 8 cycles
Subsequent treatment
- Trastuzumab maintenance (q3wk)
References
- NCCTG 983252: Perez EA, Suman VJ, Rowland KM, Ingle JN, Salim M, Loprinzi CL, Flynn PJ, Mailliard JA, Kardinal CG, Krook JE, Thrower AR, Visscher DW, Jenkins RB. Two concurrent phase II trials of paclitaxel/carboplatin/trastuzumab (weekly or every-3-week schedule) as first-line therapy in women with HER2-overexpressing metastatic breast cancer: NCCTG study 983252. Clin Breast Cancer. 2005 Dec;6(5):425-32. link to original article dosing details in abstract have been reviewed by our editors PubMed
- Robert N, Leyland-Jones B, Asmar L, Belt R, Ilegbodu D, Loesch D, Raju R, Valentine E, Sayre R, Cobleigh M, Albain K, McCullough C, Fuchs L, Slamon D. Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer. J Clin Oncol. 2006 Jun 20;24(18):2786-92. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Docetaxel & Trastuzumab (TH)
TH: Taxotere (Docetaxel) & Herceptin (Trastuzumab)
HT: Herceptin (Trastuzumab) & Taxotere (Docetaxel)
H+D: Herceptin (Trastuzumab) & Docetaxel
Regimen variant #1, 35 mg/m2 docetaxel, 3 out of 4 weeks
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Esteva et al. 2002 | Not reported | Phase 2 | ||
Burstein et al. 2007 (TRAVIOTA) | 2001-2003 | Phase 3 (E-switch-ic) | VH | Might have inferior TTP (secondary endpoint) Median TTP: 6 vs 8.5 mo |
Note: Esteva et al. 2002 described the day before the start of a cycle as "day 0," which is not the typical convention, so day -1 is being used instead.
Chemotherapy
- Docetaxel (Taxotere) 35 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, given first
Targeted therapy
- Trastuzumab (Herceptin) given second as follows:
- Cycle 1: 4 mg/kg IV over 90 minutes once on day -1, then 2 mg/kg IV over 30 minutes once per day on days 8 & 15
- Cycle 2 onwards: 2 mg/kg IV over 30 minutes once per day on days 1, 8, 15
Supportive therapy
- Dexamethasone (Decadron) 4 mg PO every 12 hours x 3 doses on cycles 1 & 2, starting the night prior to docetaxel. Patients who did not have "hypersensitivity reactions and no significant fluid retention during the first 8 weeks" received 4 mg PO twice per day on day 1 for at least the next two cycles. Patients who "remained free of fluid retention after 8 additional weeks" then received 4 mg PO once on day 1 prior to docetaxel in subsequent cycles.
28-day cycles
Regimen variant #2, 35 mg/m2 docetaxel, 7 out of 8 weeks
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Burstein et al. 2007 (TRAVIOTA) | 2001-2003 | Phase 3 (E-switch-ic) | VH | Might have inferior TTP (secondary endpoint) Median TTP: 6 vs 8.5 mo |
Chemotherapy
- Docetaxel (Taxotere) 35 mg/m2 IV once per day on days 1, 8, 15, 22, 29, 36, 43
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycle 2 onwards: 2 mg/kg IV once per day on days 1, 8, 15
8-week cycles
Regimen variant #3, 60 mg/m2 q3wk docetaxel, weekly trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Inoue et al. 2009 (JO17360) | 2004-2008 | Phase 3 (C) | H | Seems to have superior OS (co-primary endpoint) Median OS: NYR vs NYR (HR 0.37, 95% CI 0.14-0.97) |
Chemotherapy
- Docetaxel (Taxotere) 60 mg/m2 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycle 2 onwards: 2 mg/kg IV once per day on days 1, 8, 15
21-day cycles
Regimen variant #4, 75 mg/m2 q3wk docetaxel, q3wk trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hurvitz et al. 2013 (TDM4450g) | 2008-2009 | Randomized Phase 2 (C) | T-DM1 | Seems to have inferior PFS |
Baselga et al. 2011 (CLEOPATRA) | 2008-2010 | Phase 3 (C) | THP | Inferior OS1 |
Gelmon et al. 2015 (NCIC-CTG MA.31) | 2008-2011 | Phase 3 (C) | 1a. TL (Docetaxel) 1b. Lapatinib & Paclitaxel |
Superior PFS (primary endpoint) |
Perez et al. 2016 (MARIANNE) | 2010-2012 | Phase 3 (C) | 1. T-DM1 | Non-inferior PFS |
2. Pertuzumab & T-DM1 | Non-inferior PFS | |||
Hugo et al. 2017 (HERITAGE) | 2012-12-10 to 2015-08-05 | Phase 3 (C) | 1a. Docetaxel & Trastuzumab-dkst 1b. Paclitaxel & Trastuzumab-dkst |
Equivalent ORR24w (primary endpoint) ORR24w: 64% vs 69.6% |
Xu et al. 2020 (PUFFIN) | 2016-09-13 to 2017-09-28 | Phase 3 (C) | THP | Inferior PFS2 |
Xu et al. 2021 (HLX02-BC01) | 2016-11-11 to 2019-07-10 | Phase 3 (C) | Docetaxel & Trastuzumab-strf | Equivalent ORR24w (primary endpoint) ORR24w: 71.4% vs 71.3% |
Ma et al. 2023 (PHILA) | 2019-05-06 to 2022-01-17 | Phase 3 (C) | TH & Pyrotinib | Inferior PFS |
1Reported efficacy for CLEOPATRA is based on the 2020 update.
2Reported efficacy for PUFFIN is based on the 2022 update.
Note: Dose of docetaxel in TDM4450g and MARIANNE was per investigator's discretion. CLEOPATRA has an unusual schedule with both medications being given on day 2 of cycle 1, due to this regimen being the control arm, in which patients in one arm received a placebo instead of pertuzumab on day 1. It is reasonable to assume that in practice, drugs in this regimen will be given on day 1 from the beginning.
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV over 90 minutes once on day 2
- Cycle 2 onwards: 6 mg/kg IV over 30 minutes once on day 1
21-day cycle for at least 6 cycles
Subsequent treatment
- CLEOPATRA, if it is decided to no longer administer docetaxel with this regimen: patients could continue to receive trastuzumab maintenance
- NCIC-CTG MA.31: Trastuzumab maintenance, after 8 cycles
Regimen variant #5, 100 mg/m2 q3wk docetaxel, weekly trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Marty et al. 2005 (M77001) | 2000-2002 | Randomized Phase 2 (E-esc) | Docetaxel | Seems to have superior OS (secondary endpoint) Superior ORR (primary endpoint) |
Valero et al. 2010 (BCIRG 007) | 2001-2004 | Phase 3 (C) | TCH | Did not meet primary endpoint of TTP |
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV over 90 minutes once on day 1, then 2 mg/kg IV over 30 minutes once per day on days 8 & 15
- Cycles 2 to 8: 2 mg/kg IV over 30 minutes once per day on days 1, 8, 15
Supportive therapy
- Dexamethasone (Decadron) 8 mg (or equivalent) PO twice per day x 6 doses, starting the night prior to docetaxel
- "Antiemetic premedication was mandatory" (no additional details given).
21-day cycle varying durations: 6 cycles (M77001); 8 cycles (BCIRG 007)
Subsequent treatment
- M77001: Patients could receive docetaxel beyond six cycles at the discretion of the investigator. Otherwise, patients proceeded to trastuzumab maintenance.
- BCIRG 007: Trastuzumab maintenance
Regimen variant #6, 100 mg/m2 q3wk docetaxel, q3wk trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Andersson et al. 2010 (HERNATA) | 2004-2008 | Phase 3 (C) | VH | Did not meet primary endpoint of TTP |
Gianni et al. 2013 (AVAREL) | 2006-2010 | Randomized Phase 2 (C) | BTH | Might have inferior PFS |
Hurvitz et al. 2013 (TDM4450g) | 2008-2009 | Randomized Phase 2 (C) | T-DM1 | Seems to have inferior PFS |
Perez et al. 2016 (MARIANNE) | 2010-2012 | Phase 3 (E-esc) | 1. T-DM1 | Non-inferior PFS (primary endpoint) |
2. Pertuzumab & T-DM1 | Non-inferior PFS (primary endpoint) |
Note: In HERNATA, the day of docetaxel and trastuzumab were reversed in cycle 1. Dose of docetaxel in TDM4450g and MARIANNE was per investigator's discretion.
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV over 60 minutes once on day 1 (see note)
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV over 90 minutes once on day 2 (see note)
- Cycle 2 onwards: 6 mg/kg IV over 30 minutes once on day 1
21-day cycles
References
- Esteva FJ, Valero V, Booser D, Guerra LT, Murray JL, Pusztai L, Cristofanilli M, Arun B, Esmaeli B, Fritsche HA, Sneige N, Smith TL, Hortobagyi GN. Phase II study of weekly docetaxel and trastuzumab for patients with HER-2-overexpressing metastatic breast cancer. J Clin Oncol. 2002 Apr 1;20(7):1800-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- M77001: Marty M, Cognetti F, Maraninchi D, Snyder R, Mauriac L, Tubiana-Hulin M, Chan S, Grimes D, Antón A, Lluch A, Kennedy J, O'Byrne K, Conte P, Green M, Ward C, Mayne K, Extra JM. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol. 2005 Jul 1;23(19):4265-74. Epub 2005 May 23. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- TRAVIOTA: Burstein HJ, Keshaviah A, Baron AD, Hart RD, Lambert-Falls R, Marcom PK, Gelman R, Winer EP. Trastuzumab plus vinorelbine or taxane chemotherapy for HER2-overexpressing metastatic breast cancer: the trastuzumab and vinorelbine or taxane study. Cancer. 2007 Sep 1;110(5):965-72. Epub 2007 Aug 20. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00146549
- JO17360: Inoue K, Nakagami K, Mizutani M, Hozumi Y, Fujiwara Y, Masuda N, Tsukamoto F, Saito M, Miura S, Eguchi K, Shinkai T, Ando M, Watanabe T, Masuda N, Ohashi Y, Sano M, Noguchi S. Randomized phase III trial of trastuzumab monotherapy followed by trastuzumab plus docetaxel versus trastuzumab plus docetaxel as first-line therapy in patients with HER2-positive metastatic breast cancer: the JO17360 Trial Group. Breast Cancer Res Treat. 2010 Jan;119(1):127-36. Epub 2009 Aug 19. link to original article dosing details in abstract have been reviewed by our editors PubMed
- BCIRG 007: Valero V, Forbes J, Pegram MD, Pienkowski T, Eiermann W, von Minckwitz G, Roche H, Martin M, Crown J, Mackey JR, Fumoleau P, Rolski J, Mrsic-Krmpotic Z, Jagiello-Gruszfeld A, Riva A, Buyse M, Taupin H, Sauter G, Press MF, Slamon DJ. Multicenter phase III randomized trial comparing docetaxel and trastuzumab with docetaxel, carboplatin, and trastuzumab as first-line chemotherapy for patients with HER2-gene-amplified metastatic breast cancer (BCIRG 007 study): two highly active therapeutic regimens. J Clin Oncol. 2011 Jan 10;29(2):149-56. Epub 2010 Nov 29. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00047255
- HERNATA: Andersson M, Lidbrink E, Bjerre K, Wist E, Enevoldsen K, Jensen AB, Karlsson P, Tange UB, Sørensen PG, Møller S, Bergh J, Langkjer ST. Phase III randomized study comparing docetaxel plus trastuzumab with vinorelbine plus trastuzumab as first-line therapy of metastatic or locally advanced human epidermal growth factor receptor 2-positive breast cancer: the HERNATA study. J Clin Oncol. 2011 Jan 20;29(3):264-71. Epub 2010 Dec 13. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00430001
- CLEOPATRA: Baselga J, Cortés J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, Clark E, Benyunes MC, Ross G, Swain SM; CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012 Jan 12;366(2):109-19. Epub 2011 Dec 7. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00567190
- Update: Swain SM, Kim SB, Cortés J, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Knott A, Clark E, Ross G, Benyunes MC, Baselga J. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2013 May;14(6):461-71. Epub 2013 Apr 18. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
- HRQoL analysis: Cortés J, Baselga J, Im YH, Im SA, Pivot X, Ross G, Clark E, Knott A, Swain SM. Health-related quality-of-life assessment in CLEOPATRA, a phase III study combining pertuzumab with trastuzumab and docetaxel in metastatic breast cancer. Ann Oncol. 2013 Oct;24(10):2630-2635. Epub 2013 Jul 17. link to original article PubMed
- Update: Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S, Clark E, Ross G, Benyunes MC, Cortés J; CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015 Feb 19;372(8):724-34. link to original article link to PMC article PubMed
- Update: Swain SM, Miles D, Kim SB, Im YH, Im SA, Semiglazov V, Ciruelos E, Schneeweiss A, Loi S, Monturus E, Clark E, Knott A, Restuccia E, Benyunes MC, Cortés J; CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020 Apr;21(4):519-530. Epub 2020 Mar 12. link to original article PubMed
- TDM4450g: Hurvitz SA, Dirix L, Kocsis J, Bianchi GV, Lu J, Vinholes J, Guardino E, Song C, Tong B, Ng V, Chu YW, Perez EA. Phase II randomized study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2013 Mar 20;31(9):1157-63. Epub 2013 Feb 4. Erratum in: J Clin Oncol. 2013 Aug 10;31(23):2977. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00679341
- AVAREL: Gianni L, Romieu GH, Lichinitser M, Serrano SV, Mansutti M, Pivot X, Mariani P, Andre F, Chan A, Lipatov O, Chan S, Wardley A, Greil R, Moore N, Prot S, Pallaud C, Semiglazov V. AVEREL: a randomized phase III trial evaluating bevacizumab in combination with docetaxel and trastuzumab as first-line therapy for HER2-positive locally recurrent/metastatic breast cancer. J Clin Oncol. 2013 May 10;31(14):1719-25. Epub 2013 Apr 8. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00391092
- NCIC-CTG MA.31: Gelmon KA, Boyle FM, Kaufman B, Huntsman DG, Manikhas A, Di Leo A, Martin M, Schwartzberg LS, Lemieux J, Aparicio S, Shepherd LE, Dent S, Ellard SL, Tonkin K, Pritchard KI, Whelan TJ, Nomikos D, Nusch A, Coleman RE, Mukai H, Tjulandin S, Khasanov R, Rizel S, Connor AP, Santillana SL, Chapman JA, Parulekar WR. Lapatinib or trastuzumab plus taxane therapy for human epidermal growth factor receptor 2-positive advanced breast cancer: final results of NCIC-CTG MA.31. J Clin Oncol. 2015 May 10;33(14):1574-83. Epub 2015 Mar 16. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00667251
- HERITAGE: Rugo HS, Barve A, Waller CF, Hernandez-Bronchud M, Herson J, Yuan J, Sharma R, Baczkowski M, Kothekar M, Loganathan S, Manikhas A, Bondarenko I, Mukhametshina G, Nemsadze G, Parra JD, Abesamis-Tiambeng ML, Baramidze K, Akewanlop C, Vynnychenko I, Sriuranpong V, Mamillapalli G, Ray S, Yanez Ruiz EP, Pennella E; Heritage Study Investigators. Effect of a Proposed Trastuzumab Biosimilar Compared With Trastuzumab on Overall Response Rate in Patients With ERBB2 (HER2)-Positive Metastatic Breast Cancer: A Randomized Clinical Trial. JAMA. 2017 Jan 3;317(1):37-47. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02472964
- Update: Rugo HS, Pennella EJ, Gopalakrishnan U, Hernandez-Bronchud M, Herson J, Koch HF, Loganathan S, Deodhar S, Marwah A, Manikhas A, Bondarenko I, Mukhametshina G, Nemsadze G, Parra JD, Abesamis-Tiambeng MLT, Baramidze K, Akewanlop C, Vynnychenko I, Sriuranpong V, Mamillapalli G, Roy S, Yanez Ruiz EP, Barve A, Fuentes-Alburo A, Waller CF. Final overall survival analysis of the phase 3 HERITAGE study demonstrates equivalence of trastuzumab-dkst to trastuzumab in HER2-positive metastatic breast cancer. Breast Cancer Res Treat. 2021 Jul;188(2):369-377. Epub 2021 Jun 14. link to original article link to PMC article PubMed
- MARIANNE: Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, Martin M, Pienkowski T, Pivot X, Burris H 3rd, Petersen JA, Stanzel S, Strasak A, Patre M, Ellis P. Trastuzumab emtansine with or without pertuzumab versus trastuzumab plus taxane for human epidermal growth factor receptor 2-positive, advanced breast cancer: primary results from the phase III MARIANNE study. J Clin Oncol. 2017 Jan 10;35(2):141-148. Epub 2016 Nov 7. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT01120184
- Update: Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, Martin M, Pienkowski T, Pivot XB, Burris HA 3rd, Petersen JA, De Haas S, Hoersch S, Patre M, Ellis PA. Trastuzumab emtansine with or without pertuzumab versus trastuzumab with taxane for human epidermal growth factor receptor 2-positive advanced breast cancer: final results from MARIANNE. Cancer. 2019 Nov 15;125(22):3974-3984. Epub 2019 Jul 18. link to original article PubMed
- PUFFIN: Xu B, Li W, Zhang Q, Shao Z, Li Q, Wang X, Li H, Sun T, Yin Y, Zheng H, Feng J, Zhang H, Lei G, Restuccia E. Pertuzumab, trastuzumab, and docetaxel for Chinese patients with previously untreated HER2-positive locally recurrent or metastatic breast cancer (PUFFIN): a phase III, randomized, double-blind, placebo-controlled study. Breast Cancer Res Treat. 2020 Aug;182(3):689-697. Epub 2020 Jun 20. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT02896855
- Update: Xu B, Li W, Zhang Q, Li Q, Wang X, Li H, Sun T, Yin Y, Zheng H, Feng J, Zhu H, Siddiqui A, Macharia H, Knott A. Pertuzumab, trastuzumab, and docetaxel for Chinese patients with previously untreated HER2-positive locally recurrent or metastatic breast cancer (PUFFIN): final analysis of a phase III, randomized, double-blind, placebo-controlled study. Breast Cancer Res Treat. 2023 Feb;197(3):503-513. Epub 2022 Dec 4. link to original article link to PMC article PubMed
- HLX02-BC01: Xu B, Zhang Q, Sun T, Li W, Teng Y, Hu X, Bondarenko I, Adamchuk H, Zhang L, Trukhin D, Wang S, Zheng H, Tong Z, Shparyk Y, Wang Q; HLX02-BC01 Investigators. Efficacy, Safety, and Immunogenicity of HLX02 Compared with Reference Trastuzumab in Patients with Recurrent or Metastatic HER2-Positive Breast Cancer: A Randomized Phase III Equivalence Trial. BioDrugs. 2021 May;35(3):337-350. Epub 2021 Apr 7. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT03084237
- PHILA: Ma F, Yan M, Li W, Ouyang Q, Tong Z, Teng Y, Wang Y, Wang S, Geng C, Luo T, Zhong J, Zhang Q, Liu Q, Zeng X, Sun T, Mo Q, Liu H, Cheng Y, Cheng J, Wang X, Nie J, Yang J, Wu X, Wang X, Li H, Ye C, Dong F, Wu S, Zhu X, Xu B; PHILA Investigators. Pyrotinib versus placebo in combination with trastuzumab and docetaxel as first line treatment in patients with HER2 positive metastatic breast cancer (PHILA): randomised, double blind, multicentre, phase 3 trial. BMJ. 2023 Oct 31;383:e076065. Erratum in: BMJ. 2023 Nov 16;383:p2665. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT03863223
Docetaxel & Trastuzumab (TH) & Pyrotinib
TH & Pyrotinib: Taxotere (Docetaxel) & Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ma et al. 2023 (PHILA) | 2019-05-06 to 2022-01-17 | Phase 3 (E-esc) | TH | Superior PFS (primary endpoint) Median PFS: 24.3 vs 10.4 mo (HR 0.41, 95% CI 0.32-0.53) |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy
- Pyrotinib (Irene) 400 mg PO once per day on days 1 to 21
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 2
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycle for at least 6 cycles
References
- PHILA: Ma F, Yan M, Li W, Ouyang Q, Tong Z, Teng Y, Wang Y, Wang S, Geng C, Luo T, Zhong J, Zhang Q, Liu Q, Zeng X, Sun T, Mo Q, Liu H, Cheng Y, Cheng J, Wang X, Nie J, Yang J, Wu X, Wang X, Li H, Ye C, Dong F, Wu S, Zhu X, Xu B; PHILA Investigators. Pyrotinib versus placebo in combination with trastuzumab and docetaxel as first line treatment in patients with HER2 positive metastatic breast cancer (PHILA): randomised, double blind, multicentre, phase 3 trial. BMJ. 2023 Oct 31;383:e076065. Erratum in: BMJ. 2023 Nov 16;383:p2665. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT03863223
ECH
ECH: Epirubicin, Cyclophosphamide, Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Slamon et al. 2001 | 1995-1997 | Phase 3 (E-RT-esc) | 1a. AC 1b. EC |
Seems to have superior OS (secondary endpoint) Median OS: 25.1 vs 20.3 mo Superior TTP (co-primary endpoint) Median TTP: 7.4 vs 4.6 mo |
Note: This is not commonly used; here for reference purposes only.
Prior treatment criteria
- Slamon et al. 2001: No previous anthracycline exposure
Chemotherapy
- Epirubicin (Ellence) 75 mg/mg2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/mg2 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycle 2 onwards: 2 mg/kg IV once per day on days 1, 8, 15
21-day cycles
References
- Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001 Mar 15;344(11):783-92. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Lapatinib & Paclitaxel (TL)
TL: Taxol (Paclitaxel) & Lapatinib
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Guan et al. 2013 (EGF104535) | 2006-2009 | Phase 3 (E-esc) | Paclitaxel | Superior OS (primary endpoint) Median OS: 27.8 vs 20.5 mo (HR 0.74, 95% CI 0.58-0.94) |
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy
- Lapatinib (Tykerb) 1500 mg PO once per day on days 1 to 28
28-day cycles
References
- EGF104535: Guan Z, Xu B, DeSilvio ML, Shen Z, Arpornwirat W, Tong Z, Lorvidhaya V, Jiang Z, Yang J, Makhson A, Leung WL, Russo MW, Newstat B, Wang L, Chen G, Oliva C, Gomez H. Randomized trial of lapatinib versus placebo added to paclitaxel in the treatment of human epidermal growth factor receptor 2-overexpressing metastatic breast cancer. J Clin Oncol. 2013 Jun 1;31(16):1947-53. Epub 2013 Mar 18. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00281658
- NCIC-CTG MA.31: Gelmon KA, Boyle FM, Kaufman B, Huntsman DG, Manikhas A, Di Leo A, Martin M, Schwartzberg LS, Lemieux J, Aparicio S, Shepherd LE, Dent S, Ellard SL, Tonkin K, Pritchard KI, Whelan TJ, Nomikos D, Nusch A, Coleman RE, Mukai H, Tjulandin S, Khasanov R, Rizel S, Connor AP, Santillana SL, Chapman JA, Parulekar WR. Lapatinib or trastuzumab plus taxane therapy for human epidermal growth factor receptor 2-positive advanced breast cancer: final results of NCIC-CTG MA.31. J Clin Oncol. 2015 May 10;33(14):1574-83. Epub 2015 Mar 16. link to original article PubMed NCT00667251
Paclitaxel & Trastuzumab (TH)
TH: Taxol (Paclitaxel), Herceptin (Trastuzumab)
TP: Trastuzumab, Paclitaxel
Regimen variant #1, weekly paclitaxel (80 mg/m2), weekly trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Seidman et al. 2008 (CALGB 9840) | 1998 to not reported | Phase 3 (E-switch-ic) | TH; q3wk paclitaxel | Superior ORR (primary endpoint) ORR: 42% vs 29% (OR 1.75) Superior OS (secondary endpoint) Median OS: 24 vs 12 mo (HR 0.78, 95% CI 0.65-0.94) |
Burstein et al. 2007 (TRAVIOTA) | 2001-2003 | Phase 3 (E-switch-ic) | VH | Might have inferior TTP (secondary endpoint) |
Baselga et al. 2014 (STM01-102) | 2006-2009 | Phase 3 (C) | MTP | Did not meet primary endpoint of PFS |
Perez et al. 2016 (MARIANNE) | 2010-2012 | Phase 3 (C) | 1. T-DM1 | Non-inferior PFS |
2. Pertuzumab & T-DM1 | Non-inferior PFS |
Note: Different studies had different cycle lengths; this is the least divisible cycle length.
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1
- Cycle 2 onwards: 2 mg/kg IV once on day 1
7-day cycles
Regimen variant #2, weekly paclitaxel (80 mg/m2), q3wk trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hugo et al. 2017 (HERITAGE) | 2012-12-10 to 2015-08-05 | Phase 3 (C) | 1a. Docetaxel & Trastuzumab-dkst 1b. Paclitaxel & Trastuzumab-dkst |
Equivalent ORR24w (primary endpoint) ORR24w: 64% vs 69.6% |
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV over 90 minutes once on day 1
- Cycle 2 onwards: 6 mg/kg IV over 60 minutes once on day 1
21-day cycles
Regimen variant #3, weekly paclitaxel (90 mg/m2)
Study | Dates of enrollment | Evidence |
---|---|---|
Seidman et al. 2001 | Not reported | Phase 2 |
Chemotherapy
- Paclitaxel (Taxol) 90 mg/m2 IV once per day on days 1, 8, 15, 22
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 0, then 2 mg/kg IV once per day on days 8, 15, 22
- Cycle 2 onwards: 2 mg/kg IV once per day on days 1, 8, 15, 22
28-day cycles
Regimen variant #4, paclitaxel 3 weeks out of 4, 6 cycles
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gelmon et al. 2015 (NCIC-CTG MA.31) | 2008-2011 | Phase 3 (C) | 1a. TL (Docetaxel) 1b. Lapatinib & Paclitaxel |
Superior PFS (primary endpoint) |
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22
- Cycles 2 to 6: 2 mg/kg IV once per day on days 1, 8, 15, 22
28-day cycle for 6 cycles
Subsequent treatment
- Trastuzumab maintenance
Regimen variant #5, paclitaxel 3 weeks out of 4, indefinite
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hurvitz et al. 2015 (BOLERO-1) | 2009-2012 | Phase 3 (C) | TH & Everolimus | Did not meet primary endpoint of PFS |
Awada et al. 2016 (NEfERT-T) | 2009-2014 | Phase 3 (C) | Neratinib & Paclitaxel | Did not meet primary endpoint of PFS |
Pegram et al. 2018 (REFLECTIONS B327-02) | 2014-04-04 to 2016-01-22 | Phase 3 (C) | Paclitaxel & Trastuzumab-bvzr | Equivalent ORR (primary endpoint) ORR: 66.5% vs 62.5% |
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV over 60 minutes once per day on days 1, 8, 15
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22
- Cycle 2 onwards: 2 mg/kg IV once per day on days 1, 8, 15, 22
28-day cycles
Regimen variant #6, q3wk paclitaxel, weekly trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Slamon et al. 2001 | 1995-1997 | Phase 3 (E-RT-esc) | Paclitaxel | Seems to have superior OS (secondary endpoint) Median OS: 25.1 vs 20.3 mo Superior TTP (co-primary endpoint) Median TTP: 7.4 vs 4.6 mo |
Robert et al. 2006 | 1998-2002 | Phase 3 (C) | TPC | Inferior PFS |
Seidman et al. 2008 (CALGB 9840) | 1998 to not reported | Phase 3 (C) | TH; weekly paclitaxel (80 mg/m2) | Inferior OS |
Prior treatment criteria
- Slamon et al. 2001: Previous anthracycline exposure
Chemotherapy
- Paclitaxel (Taxol) as follows:
- Cycles 1 to 6: 175 mg/m2 IV once on day 2
- Cycle 7 onwards: continued at investigator's discretion
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycle 2 onwards: 2 mg/kg IV once per day on days 1, 8, 15
21-day cycle for at least 6 cycles
Regimen variant #7, q3wk paclitaxel, q3wk trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Alexeev et al. 2020 (BCD-022-02) | 2012-10 to 2017-12 | Phase 3 (C) | TH (biosimilar trastuzumab) | Equivalent ORR (primary endpoint) ORR: 43.6% vs 49.6% |
Chemotherapy
- Paclitaxel (Taxol) as follows:
- Cycles 1 to 6: 175 mg/m2 IV once on day 2
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
References
- Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001 Mar 15;344(11):783-92. link to original article PubMed
- Seidman AD, Fornier MN, Esteva FJ, Tan L, Kaptain S, Bach A, Panageas KS, Arroyo C, Valero V, Currie V, Gilewski T, Theodoulou M, Moynahan ME, Moasser M, Sklarin N, Dickler M, D'Andrea G, Cristofanilli M, Rivera E, Hortobagyi GN, Norton L, Hudis CA. Weekly trastuzumab and paclitaxel therapy for metastatic breast cancer with analysis of efficacy by HER2 immunophenotype and gene amplification. J Clin Oncol. 2001 May 15;19(10):2587-95. link to original article PubMed
- Robert N, Leyland-Jones B, Asmar L, Belt R, Ilegbodu D, Loesch D, Raju R, Valentine E, Sayre R, Cobleigh M, Albain K, McCullough C, Fuchs L, Slamon D. Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer. J Clin Oncol. 2006 Jun 20;24(18):2786-92. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- TRAVIOTA: Burstein HJ, Keshaviah A, Baron AD, Hart RD, Lambert-Falls R, Marcom PK, Gelman R, Winer EP. Trastuzumab plus vinorelbine or taxane chemotherapy for HER2-overexpressing metastatic breast cancer: the trastuzumab and vinorelbine or taxane study. Cancer. 2007 Sep 1;110(5):965-72. Epub 2007 Aug 20. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00146549
- CALGB 9840: Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom PK, Gipson G, Burstein H, Lake D, Shapiro CL, Ungaro P, Norton L, Winer E, Hudis C. Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol. 2008 Apr 1;26(10):1642-9. link to original article PubMed NCT00003440
- STM01-102: Baselga J, Manikhas A, Cortés J, Llombart A, Roman L, Semiglazov VF, Byakhov M, Lokanatha D, Forenza S, Goldfarb RH, Matera J, Azarnia N, Hudis CA, Rozencweig M. Phase III trial of nonpegylated liposomal doxorubicin in combination with trastuzumab and paclitaxel in HER2-positive metastatic breast cancer. Ann Oncol. 2014 Mar;25(3):592-8. Epub 2014 Jan 8. link to original article link to PMC article dosing details in abstract have been reviewed by our editors PubMed NCT00294996
- NCIC-CTG MA.31: Gelmon KA, Boyle FM, Kaufman B, Huntsman DG, Manikhas A, Di Leo A, Martin M, Schwartzberg LS, Lemieux J, Aparicio S, Shepherd LE, Dent S, Ellard SL, Tonkin K, Pritchard KI, Whelan TJ, Nomikos D, Nusch A, Coleman RE, Mukai H, Tjulandin S, Khasanov R, Rizel S, Connor AP, Santillana SL, Chapman JA, Parulekar WR. Lapatinib or trastuzumab plus taxane therapy for human epidermal growth factor receptor 2-positive advanced breast cancer: final results of NCIC-CTG MA.31. J Clin Oncol. 2015 May 10;33(14):1574-83. Epub 2015 Mar 16. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00667251
- BOLERO-1: Hurvitz SA, Andre F, Jiang Z, Shao Z, Mano MS, Neciosup SP, Tseng LM, Zhang Q, Shen K, Liu D, Dreosti LM, Burris HA, Toi M, Buyse ME, Cabaribere D, Lindsay MA, Rao S, Pacaud LB, Taran T, Slamon D. Combination of everolimus with trastuzumab plus paclitaxel as first-line treatment for patients with HER2-positive advanced breast cancer (BOLERO-1): a phase 3, randomised, double-blind, multicentre trial. Lancet Oncol. 2015 Jul;16(7):816-29. Epub 2015 Jun 16. link to original article PubMed NCT00876395
- MARIANNE: Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, Martin M, Pienkowski T, Pivot X, Burris H 3rd, Petersen JA, Stanzel S, Strasak A, Patre M, Ellis P. Trastuzumab emtansine with or without pertuzumab versus trastuzumab plus taxane for human epidermal growth factor receptor 2-positive, advanced breast cancer: primary results from the phase III MARIANNE study. J Clin Oncol. 2017 Jan 10;35(2):141-148. Epub 2016 Nov 7. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT01120184
- Update: Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, Martin M, Pienkowski T, Pivot XB, Burris HA 3rd, Petersen JA, De Haas S, Hoersch S, Patre M, Ellis PA. Trastuzumab emtansine with or without pertuzumab versus trastuzumab with taxane for human epidermal growth factor receptor 2-positive advanced breast cancer: final results from MARIANNE. Cancer. 2019 Nov 15;125(22):3974-3984. Epub 2019 Jul 18. link to original article PubMed
- NEfERT-T: Awada A, Colomer R, Inoue K, Bondarenko I, Badwe RA, Demetriou G, Lee SC, Mehta AO, Kim SB, Bachelot T, Goswami C, Deo S, Bose R, Wong A, Xu F, Yao B, Bryce R, Carey LA. neratinib plus paclitaxel vs trastuzumab plus paclitaxel in previously untreated metastatic ERBB2-positive breast cancer: The NEfERT-T randomized clinical trial. JAMA Oncol. 2016 Dec 1;2(12):1557-1564. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00915018
- HERITAGE: Rugo HS, Barve A, Waller CF, Hernandez-Bronchud M, Herson J, Yuan J, Sharma R, Baczkowski M, Kothekar M, Loganathan S, Manikhas A, Bondarenko I, Mukhametshina G, Nemsadze G, Parra JD, Abesamis-Tiambeng ML, Baramidze K, Akewanlop C, Vynnychenko I, Sriuranpong V, Mamillapalli G, Ray S, Yanez Ruiz EP, Pennella E; Heritage Study Investigators. Effect of a Proposed Trastuzumab Biosimilar Compared With Trastuzumab on Overall Response Rate in Patients With ERBB2 (HER2)-Positive Metastatic Breast Cancer: A Randomized Clinical Trial. JAMA. 2017 Jan 3;317(1):37-47. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02472964
- Update: Rugo HS, Pennella EJ, Gopalakrishnan U, Hernandez-Bronchud M, Herson J, Koch HF, Loganathan S, Deodhar S, Marwah A, Manikhas A, Bondarenko I, Mukhametshina G, Nemsadze G, Parra JD, Abesamis-Tiambeng MLT, Baramidze K, Akewanlop C, Vynnychenko I, Sriuranpong V, Mamillapalli G, Roy S, Yanez Ruiz EP, Barve A, Fuentes-Alburo A, Waller CF. Final overall survival analysis of the phase 3 HERITAGE study demonstrates equivalence of trastuzumab-dkst to trastuzumab in HER2-positive metastatic breast cancer. Breast Cancer Res Treat. 2021 Jul;188(2):369-377. Epub 2021 Jun 14. link to original article link to PMC article PubMed
- REFLECTIONS B327-02: Pegram MD, Bondarenko I, Zorzetto MMC, Hingmire S, Iwase H, Krivorotko PV, Lee KS, Li RK, Pikiel J, Aggarwal R, Ewesuedo R, Freyman A, Li R, Vana A, Yin D, Zacharchuk C, Tan-Chiu E. PF-05280014 (a trastuzumab biosimilar) plus paclitaxel compared with reference trastuzumab plus paclitaxel for HER2-positive metastatic breast cancer: a randomised, double-blind study. Br J Cancer. 2019 Jan;120(2):172-182. Epub 2018 Dec 20. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT01989676
- Update: Li RK, Tokunaga E, Adamchuk H, Vladimirov V, Yanez E, Lee KS, Bondarenko I, Vana A, Hilton F, Ishikawa T, Tajima K, Lipatov O. Long-Term Safety and Effectiveness of PF-05280014 (a Trastuzumab Biosimilar) Treatment in Patients with HER2-Positive Metastatic Breast Cancer: Updated Results of a Randomized, Double-Blind Study. BioDrugs. 2022 Jan;36(1):55-69. Epub 2022 Feb 8. link to original article link to PMC article PubMed
- BCD-022-02: Alexeev SM, Khorinko AV, Mukhametshina GZ, Shelepen KG, Burdaeva ON, Kulik SA, Satheesh CT, Srivastava K, Vikranth M, Kryukov F, Paltusova AN, Shustova MS, Ivanov RA. Randomized double-blind clinical trial comparing safety and efficacy of the biosimilar BCD-022 with reference trastuzumab. BMC Cancer. 2020 Aug 20;20(1):783. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT01764022
nab-Paclitaxel & Trastuzumab
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Mirtsching et al. 2011 | 2005-2006 | Phase 2 |
Chemotherapy
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 125 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV over 90 minutes once on day 1, then 2 mg/kg IV over 30 minutes once per day on days 8, 15, 22
- Cycle 2 onwards: 2 mg/kg IV over 30 minutes once per day on days 1, 8, 15, 22
28-day cycles
References
- Mirtsching B, Cosgriff T, Harker G, Keaton M, Chidiac T, Min M. A phase II study of weekly nanoparticle albumin-bound paclitaxel with or without trastuzumab in metastatic breast cancer. Clin Breast Cancer. 2011 Apr;11(2):121-8. Epub 2011 Apr 11. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Pertuzumab & T-DM1
Pertuzumab & T-DM1: Pertuzumab & Trastuzumab-DM1 (Trastuzumab emtansine)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Perez et al. 2016 (MARIANNE) | 2010-2012 | Phase 3 (E-esc) | 1. T-DM1 | Non-inferior PFS (primary endpoint) Median PFS: 15.2 vs 14.1 mo |
2a. TH (Docetaxel) 2b. TH (Paclitaxel) |
Non-inferior PFS (primary endpoint) Median PFS: 15.2 vs 13.7 mo |
Targeted therapy
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycle 2 onwards: 420 mg IV once on day 1
Antibody-drug conjugate therapy
- Trastuzumab emtansine (Kadcyla) 3.6 mg/kg IV once on day 1
21-day cycles
References
- MARIANNE: Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, Martin M, Pienkowski T, Pivot X, Burris H 3rd, Petersen JA, Stanzel S, Strasak A, Patre M, Ellis P. Trastuzumab emtansine with or without pertuzumab versus trastuzumab plus taxane for human epidermal growth factor receptor 2-positive, advanced breast cancer: primary results from the phase III MARIANNE study. J Clin Oncol. 2017 Jan 10;35(2):141-148. Epub 2016 Nov 7. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT01120184
- Update: Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, Martin M, Pienkowski T, Pivot XB, Burris HA 3rd, Petersen JA, De Haas S, Hoersch S, Patre M, Ellis PA. Trastuzumab emtansine with or without pertuzumab versus trastuzumab with taxane for human epidermal growth factor receptor 2-positive advanced breast cancer: final results from MARIANNE. Cancer. 2019 Nov 15;125(22):3974-3984. Epub 2019 Jul 18. link to original article PubMed
TCH (Docetaxel)
TCH: Taxotere (Docetaxel), Carboplatin, Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Valero et al. 2011 (BCIRG 007) | 2001-2004 | Phase 3 (E-esc) | TH | Did not meet primary endpoint of TTP Median TTP: 10.4 vs 11.1 mo (HR 1.09, 95% CI 0.83-1.44) |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 2 to 8: 2 mg/kg IV once per day on days 1, 8, 15
21-day cycle for 8 cycles
Subsequent treatment
- Trastuzumab maintenance
References
- BCIRG 007: Valero V, Forbes J, Pegram MD, Pienkowski T, Eiermann W, von Minckwitz G, Roche H, Martin M, Crown J, Mackey JR, Fumoleau P, Rolski J, Mrsic-Krmpotic Z, Jagiello-Gruszfeld A, Riva A, Buyse M, Taupin H, Sauter G, Press MF, Slamon DJ. Multicenter phase III randomized trial comparing docetaxel and trastuzumab with docetaxel, carboplatin, and trastuzumab as first-line chemotherapy for patients with HER2-gene-amplified metastatic breast cancer (BCIRG 007 study): two highly active therapeutic regimens. J Clin Oncol. 2011 Jan 10;29(2):149-56. Epub 2010 Nov 29. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00047255
THP (Docetaxel)
THP: Taxotere (Docetaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Baselga et al. 2011 (CLEOPATRA) | 2008-2010 | Phase 3 (E-RT-esc) | Docetaxel & Trastuzumab | Superior PFS (primary endpoint) Median PFS: 18.5 vs 12.4 mo (HR 0.62, 95% CI 0.51-0.75) Superior OS1 (secondary endpoint) Median OS: 57.1 vs 40.8 mo (HR 0.69, 95% CI 0.58-0.82) |
Xu et al. 2020 (PUFFIN) | 2016-09-13 to 2017-09-28 | Phase 3 (E-esc) | Docetaxel & Trastuzumab | Superior PFS2 (primary endpoint) Median PFS: 16.5 vs 12.5 mo (HR 0.60, 95% CI 0.45-0.81) Might have superior OS2 (secondary endpoint) Median OS: NYR vs NYR (HR 0.68, 95% CI 0.45-1.03) |
1Reported efficacy for CLEOPATRA is based on the 2020 update.
2Reported efficacy for PUFFIN is based on the 2022 update.
Chemotherapy
- Docetaxel (Taxotere) given third as follows:
- Cycle 1: 75 mg/m2 IV once on day 2
- Cycle 2 onwards: 75 mg/m2 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV over 90 minutes once on day 2
- Cycle 2 onwards: 6 mg/kg IV over 30 to 90 minutes once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV over 60 minutes once on day 1
- Cycle 2 onwards: 420 mg IV over 30 to 60 minutes once on day 1
21-day cycle for at least 6 cycles
Subsequent treatment
- CLEOPATRA, if it is decided to no longer administer docetaxel: patients could continue to receive pertuzumab & trastuzumab maintenance.
References
- CLEOPATRA: Baselga J, Cortés J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, Clark E, Benyunes MC, Ross G, Swain SM; CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012 Jan 12;366(2):109-19. Epub 2011 Dec 7. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00567190
- Update: Swain SM, Kim SB, Cortés J, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Knott A, Clark E, Ross G, Benyunes MC, Baselga J. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2013 May;14(6):461-71. Epub 2013 Apr 18. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
- HRQoL analysis: Cortés J, Baselga J, Im YH, Im SA, Pivot X, Ross G, Clark E, Knott A, Swain SM. Health-related quality-of-life assessment in CLEOPATRA, a phase III study combining pertuzumab with trastuzumab and docetaxel in metastatic breast cancer. Ann Oncol. 2013 Oct;24(10):2630-2635. Epub 2013 Jul 17. link to original article PubMed
- Update: Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S, Clark E, Ross G, Benyunes MC, Cortés J; CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015 Feb 19;372(8):724-34. link to original article link to PMC article PubMed
- Update: Swain SM, Miles D, Kim SB, Im YH, Im SA, Semiglazov V, Ciruelos E, Schneeweiss A, Loi S, Monturus E, Clark E, Knott A, Restuccia E, Benyunes MC, Cortés J; CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020 Apr;21(4):519-530. Epub 2020 Mar 12. link to original article PubMed
- PUFFIN: Xu B, Li W, Zhang Q, Shao Z, Li Q, Wang X, Li H, Sun T, Yin Y, Zheng H, Feng J, Zhang H, Lei G, Restuccia E. Pertuzumab, trastuzumab, and docetaxel for Chinese patients with previously untreated HER2-positive locally recurrent or metastatic breast cancer (PUFFIN): a phase III, randomized, double-blind, placebo-controlled study. Breast Cancer Res Treat. 2020 Aug;182(3):689-697. Epub 2020 Jun 20. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT02896855
- Update: Xu B, Li W, Zhang Q, Li Q, Wang X, Li H, Sun T, Yin Y, Zheng H, Feng J, Zhu H, Siddiqui A, Macharia H, Knott A. Pertuzumab, trastuzumab, and docetaxel for Chinese patients with previously untreated HER2-positive locally recurrent or metastatic breast cancer (PUFFIN): final analysis of a phase III, randomized, double-blind, placebo-controlled study. Breast Cancer Res Treat. 2023 Feb;197(3):503-513. Epub 2022 Dec 4. link to original article link to PMC article PubMed
- HERB TEA: UMIN000030783
Trastuzumab monotherapy
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pagani et al. 2017 (SAKK 22/99) | 1999-2013 | Phase 3 (C) | Chemotherapy & Trastuzumab | Did not meet primary endpoint of TTP |
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1
- Cycle 2 onwards: 2 mg/kg IV once on day 1
7-day cycles
Regimen variant #2, flat dose
Historic variant |
Study | Dates of enrollment | Evidence |
---|---|---|
Baselga et al. 1996 | Not reported | Phase 2 |
Note: this variant is of historical interest, only.
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 250 mg IV once on day 1
- Cycles 2 to 11: 100 mg IV once on day 1
7-day cycle for 11 cycles
References
- Baselga J, Tripathy D, Mendelsohn J, Baughman S, Benz CC, Dantis L, Sklarin NT, Seidman AD, Hudis CA, Moore J, Rosen PP, Twaddell T, Henderson IC, Norton L. Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. J Clin Oncol. 1996 Mar;14(3):737-44. link to original article PubMed
- SAKK 22/99: Pagani O, Klingbiel D, Ruhstaller T, Nolè F, Eppenberger S, Oehlschlegel C, Bernhard J, Brauchli P, Hess D, Mamot C, Munzone E, Pestalozzi B, Rabaglio M, Aebi S, Ribi K, Rochlitz C, Rothgiesser K, Thürlimann B, von Moos R, Zaman K, Goldhirsch A; Swiss Group for Clinical Cancer Research. Do all patients with advanced HER2 positive breast cancer need upfront-chemo when receiving trastuzumab? Randomized phase III trial SAKK 22/99. Ann Oncol. 2017 Feb 1;28(2):305-312. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00004935
Trastuzumab emtansine monotherapy
T-DM1: Trastuzumab-DM1 (Trastuzumab emtansine)
Example orders
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hurvitz et al. 2013 (TDM4450g) | 2008-2009 | Randomized Phase 2 (E-switch-ooc) | TH | Seems to have superior PFS (co-primary endpoint) Median PFS: 14.2 vs 9.2 mo (HR 0.59, 95% CI 0.36-0.97) |
Perez et al. 2016 (MARIANNE) | 2010-2012 | Phase 3 (E-de-esc) | 1. T-DM1 & Pertuzumab | Non-inferior PFS (primary endpoint) |
2a. TH (Docetaxel) 2b. TH (Paclitaxel) |
Non-inferior PFS (primary endpoint) |
Antibody-drug conjugate therapy
- Trastuzumab emtansine (Kadcyla) 3.6 mg/kg IV once on day 1
21-day cycles
References
- TDM4450g: Hurvitz SA, Dirix L, Kocsis J, Bianchi GV, Lu J, Vinholes J, Guardino E, Song C, Tong B, Ng V, Chu YW, Perez EA. Phase II randomized study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2013 Mar 20;31(9):1157-63. Epub 2013 Feb 4. Erratum in: J Clin Oncol. 2013 Aug 10;31(23):2977. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00679341
- MARIANNE: Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, Martin M, Pienkowski T, Pivot X, Burris H 3rd, Petersen JA, Stanzel S, Strasak A, Patre M, Ellis P. Trastuzumab emtansine with or without pertuzumab versus trastuzumab plus taxane for human epidermal growth factor receptor 2-positive, advanced breast cancer: primary results from the phase III MARIANNE study. J Clin Oncol. 2017 Jan 10;35(2):141-148. Epub 2016 Nov 7. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT01120184
- Update: Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, Martin M, Pienkowski T, Pivot XB, Burris HA 3rd, Petersen JA, De Haas S, Hoersch S, Patre M, Ellis PA. Trastuzumab emtansine with or without pertuzumab versus trastuzumab with taxane for human epidermal growth factor receptor 2-positive advanced breast cancer: final results from MARIANNE. Cancer. 2019 Nov 15;125(22):3974-3984. Epub 2019 Jul 18. link to original article PubMed
Vinorelbine & Trastuzumab (VH)
VH: Vinorelbine & Herceptin (Trastuzumab)
Regimen variant #1, vinorelbine 25 mg/m2, weekly
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Burstein et al. 2007 (TRAVIOTA) | 2001-2003 | Phase 3 (E-switch-ic) | 1a. TH (Docetaxel) 1b. TH (Paclitaxel) |
Might have superior TTP (primary endpoint) |
Chemotherapy
- Vinorelbine (Navelbine) 25 mg/m2 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1
- Cycle 2 onwards: 2 mg/kg IV once on day 1
7-day cycles
Regimen variant #2, vinorelbine 30 mg/m2, 2 out of 3 weeks
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Andersson et al. 2010 (HERNATA) | 2004-2008 | Phase 3 (E-switch-ic) | TH (Docetaxel) | Did not meet primary endpoint of TTP |
Chemotherapy
- Vinorelbine (Navelbine) 30 mg/m2 IV once per day on days 1 & 8
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV over 90 minutes once on day 1
- Cycle 2 onwards: 6 mg/kg IV over 30 minutes once on day 1
21-day cycles
Regimen variant #3, vinorelbine 35 mg/m2, 2 out of 3 weeks
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Andersson et al. 2010 (HERNATA) | 2004-2008 | Phase 3 (E-switch-ic) | TH (Docetaxel) | Did not meet primary endpoint of TTP |
Chemotherapy
- Vinorelbine (Navelbine) 35 mg/m2 IV once per day on days 1 & 8
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV over 90 minutes once on day 1
- Cycle 2 onwards: 6 mg/kg IV over 30 minutes once on day 1
21-day cycles
References
- TRAVIOTA: Burstein HJ, Keshaviah A, Baron AD, Hart RD, Lambert-Falls R, Marcom PK, Gelman R, Winer EP. Trastuzumab plus vinorelbine or taxane chemotherapy for HER2-overexpressing metastatic breast cancer: the trastuzumab and vinorelbine or taxane study. Cancer. 2007 Sep 1;110(5):965-72. Epub 2007 Aug 20. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00146549
- HERNATA: Andersson M, Lidbrink E, Bjerre K, Wist E, Enevoldsen K, Jensen AB, Karlsson P, Tange UB, Sørensen PG, Møller S, Bergh J, Langkjer ST. Phase III randomized study comparing docetaxel plus trastuzumab with vinorelbine plus trastuzumab as first-line therapy of metastatic or locally advanced human epidermal growth factor receptor 2-positive breast cancer: the HERNATA study. J Clin Oncol. 2011 Jan 20;29(3):264-71. Epub 2010 Dec 13. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00430001
Metastatic or unresectable disease, subsequent lines
Capecitabine & Lapatinib
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Geyer et al. 2006 (EGF100151) | 2004-03-29 to 2005-11-15 | Phase 3 (E-RT-esc) | Capecitabine | Superior TTP1 (primary endpoint) (HR 0.57, 95% CI 0.43-0.77) Did not meet secondary endpoint of OS Median OS: 75 vs 64.7 weeks (HR 0.87, 95% CI 0.71-1.08) |
Verma et al. 2012 (EMILIA) | 2009-2011 | Phase 3 (C) | T-DM1 | Inferior OS |
Pivot et al. 2015 (CEREBEL) | 2009-2012 | Phase 3 (E-switch-ic) | Capecitabine & Trastuzumab | Did not meet primary endpoint of CNS metastases as first site of relapse |
Saura et al. 2020 (NALA) | 2013-2017 | Phase 3 (C) | Capecitabine & Neratinib | Inferior PFS |
Xu et al. 2021 (PHOEBE) | 2017-07-31 to 2018-10-30 | Phase 3 (C) | Capecitabine & Pyrotinib | Inferior PFS |
André et al. 2023 (DESTINY-Breast02) | 2018-09-06 to 2020-12-31 | Phase 3 (C) | T-DXd | Inferior PFS |
1Reported efficacy for PFS for EGF100151 is based on the 2008 update.
2Reported efficacy for OS for EGF100151 is based on the 2010 update.
Note: the primary endpoint of CEREBEL was incidence of CNS as site of first relapse; this was very low in both arms, with no statistically significant difference.
Prior treatment criteria
- EGF100151: an anthracycline, a taxane, and trastuzumab
- EMILIA, PHOEBE, DESTINY-Breast02: trastuzumab and a taxane
- CEREBEL: prior anthracycline and/or taxanes
- NALA: 2 or more previous HER2-directed therapies in the metastatic setting
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
Targeted therapy
- Lapatinib (Tykerb) 1250 mg PO once per day on days 1 to 21
21-day cycles
References
- EGF100151: Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006 Dec 28;355(26):2733-43. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00078572
- Update: Cameron D, Casey M, Press M, Lindquist D, Pienkowski T, Romieu CG, Chan S, Jagiello-Gruszfeld A, Kaufman B, Crown J, Chan A, Campone M, Viens P, Davidson N, Gorbounova V, Raats JI, Skarlos D, Newstat B, Roychowdhury D, Paoletti P, Oliva C, Rubin S, Stein S, Geyer CE. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat. 2008 Dec;112(3):533-43. Epub 2008 Jan 11. link to original article PubMed
- Update: Cameron D, Casey M, Oliva C, Newstat B, Imwalle B, Geyer CE. Lapatinib plus capecitabine in women with HER-2-positive advanced breast cancer: final survival analysis of a phase III randomized trial. Oncologist. 2010;15(9):924-34. Epub 2010 Aug 24. link to original article link to PMC article PubMed
- EMILIA: Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh DY, Diéras V, Guardino E, Fang L, Lu MW, Olsen S, Blackwell K; EMILIA Study Group. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012 Nov 8;367(19):1783-91. Epub 2012 Oct 1. Erratum in: N Engl J Med. 2013 Jun 20;368(25):2442. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00829166
- PRO analysis: Welslau M, Diéras V, Sohn JH, Hurvitz SA, Lalla D, Fang L, Althaus B, Guardino E, Miles D. Patient-reported outcomes from EMILIA, a randomized phase 3 study of trastuzumab emtansine (T-DM1) versus capecitabine and lapatinib in human epidermal growth factor receptor 2-positive locally advanced or metastatic breast cancer. Cancer. 2014 Mar 1;120(5):642-51. Epub 2013 Nov 12. link to original article PubMed
- Update: Diéras V, Miles D, Verma S, Pegram M, Welslau M, Baselga J, Krop IE, Blackwell K, Hoersch S, Xu J, Green M, Gianni L. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2017 Jun;18(6):732-742. Epub 2017 May 16. link to original article link to PMC article PubMed
- CEREBEL: Pivot X, Manikhas A, Żurawski B, Chmielowska E, Karaszewska B, Allerton R, Chan S, Fabi A, Bidoli P, Gori S, Ciruelos E, Dank M, Hornyak L, Margolin S, Nusch A, Parikh R, Nagi F, DeSilvio M, Santillana S, Swaby RF, Semiglazov V. CEREBEL (EGF111438): A phase III, randomized, open-label study of lapatinib plus capecitabine versus trastuzumab plus capecitabine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2015 May 10;33(14):1564-73. Epub 2015 Jan 20. link to original article PubMed NCT00820222
- NALA: Saura C, Oliveira M, Feng YH, Dai MS, Chen SW, Hurvitz SA, Kim SB, Moy B, Delaloge S, Gradishar W, Masuda N, Palacova M, Trudeau ME, Mattson J, Yap YS, Hou MF, De Laurentiis M, Yeh YM, Chang HT, Yau T, Wildiers H, Haley B, Fagnani D, Lu YS, Crown J, Lin J, Takahashi M, Takano T, Yamaguchi M, Fujii T, Yao B, Bebchuk J, Keyvanjah K, Bryce R, Brufsky A; NALA Investigators. Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial. J Clin Oncol. 2020 Sep 20;38(27):3138-3149. Epub 2020 Jul 17. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01808573
- PHOEBE: Xu B, Yan M, Ma F, Hu X, Feng J, Ouyang Q, Tong Z, Li H, Zhang Q, Sun T, Wang X, Yin Y, Cheng Y, Li W, Gu Y, Chen Q, Liu J, Cheng J, Geng C, Qin S, Wang S, Lu J, Shen K, Liu Q, Wang X, Wang H, Luo T, Yang J, Wu Y, Yu Z, Zhu X, Chen C, Zou J; PHOEBE Investigators. Pyrotinib plus capecitabine versus lapatinib plus capecitabine for the treatment of HER2-positive metastatic breast cancer (PHOEBE): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2021 Mar;22(3):351-360. Epub 2021 Feb 11. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT03080805
- DESTINY-Breast02: André F, Hee Park Y, Kim SB, Takano T, Im SA, Borges G, Lima JP, Aksoy S, Gavila Gregori J, De Laurentiis M, Bianchini G, Roylance R, Miyoshi Y, Armstrong A, Sinha R, Ruiz Borrego M, Lim E, Ettl J, Yerushalmi R, Zagouri F, Duhoux FP, Fehm T, Gambhire D, Cathcart J, Wu C, Chu C, Egorov A, Krop I. Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2023 May 27;401(10390):1773-1785. Epub 2023 Apr 20. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT03523585
- PRO analysis: Fehm T, Cottone F, Dunton K, André F, Krop I, Park YH, De Laurentiis M, Miyoshi Y, Armstrong A, Borrego MR, Yerushalmi R, Duhoux FP, Takano T, Lu W, Egorov A, Kim SB. Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): patient-reported outcomes from a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2024 May;25(5):614-625. link to original article PubMed
Capecitabine & Margetuximab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rugo et al. 2021 (SOPHIA) | 2015-2018 | Phase 3 (E-RT-switch-ic) | 1a. Eribulin & Trastuzumab 1b. Gemcitabine & Trastuzumab 1c. VH 1d. XH |
Seems to have superior PFS (primary endpoint) Median PFS: 6 vs 5 mo (HR 0.76, 95% CI 0.59-0.98) Did not meet secondary endpoint of OS1 Median OS: 21.6 vs 21.9 mo (HR 0.95, 95% CI 0.77-1.17) |
1Reported efficacy is based on the 2022 update.
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
Targeted therapy
- Margetuximab (Margenza) 15 mg/kg IV over 120 minutes once on day 1
21-day cycles
References
- SOPHIA: Rugo HS, Im SA, Cardoso F, Cortés J, Curigliano G, Musolino A, Pegram MD, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Kaufman B, Yerushalmi R, Fasching PA, Nordstrom JL, Bonvini E, Koenig S, Edlich S, Hong S, Rock EP, Gradishar WJ; SOPHIA Study Group. Efficacy of Margetuximab vs Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Apr 1;7(4):573-584. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT02492711
- Update: Rugo HS, Im SA, Cardoso F, Cortes J, Curigliano G, Musolino A, Pegram MD, Bachelot T, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Schwartz GN, Pluard TJ, Ricci F, Gwin WR 3rd, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Gal-Yam EN, Yerushalmi R, Fasching PA, Kaufman PA, Ashley EJ, Perez-Olle R, Hong S, Rosales MK, Gradishar WJ; SOPHIA Study Group. Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial. J Clin Oncol. 2023 Jan 10;41(2):198-205. Epub 2022 Nov 4. link to original article link to PMC article PubMed
Capecitabine & Neratinib
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Saura et al. 2014 (3144A1-2206) | 2008 to not reported | Phase 1/2 | ORR: 64% | |
Saura et al. 2020 (NALA) | 2013-2017 | Phase 3 (E-RT-switch-ic) | Capecitabine & Lapatinib | Superior PFS (primary endpoint) Median PFS: 8.8 vs 6.6 mo (HR 0.76, 95% CI 0.63-0.93) |
Chemotherapy
- Capecitabine (Xeloda) 750 mg/m2 PO twice per day on days 1 to 14
Targeted therapy
- Neratinib (Nerlynx) 240 mg PO once per day on days 1 to 21
21-day cycles
References
- 3144A1-2206: Saura C, Garcia-Saenz JA, Xu B, Harb W, Moroose R, Pluard T, Cortés J, Kiger C, Germa C, Wang K, Martin M, Baselga J, Kim SB. Safety and efficacy of neratinib in combination with capecitabine in patients with metastatic human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2014 Nov 10;32(32):3626-33. Epub 2014 Oct 6. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00741260
- NALA: Saura C, Oliveira M, Feng YH, Dai MS, Chen SW, Hurvitz SA, Kim SB, Moy B, Delaloge S, Gradishar W, Masuda N, Palacova M, Trudeau ME, Mattson J, Yap YS, Hou MF, De Laurentiis M, Yeh YM, Chang HT, Yau T, Wildiers H, Haley B, Fagnani D, Lu YS, Crown J, Lin J, Takahashi M, Takano T, Yamaguchi M, Fujii T, Yao B, Bebchuk J, Keyvanjah K, Bryce R, Brufsky A; NALA Investigators. Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial. J Clin Oncol. 2020 Sep 20;38(27):3138-3149. Epub 2020 Jul 17. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01808573
Capecitabine & Pyrotinib
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Xu et al. 2021 (PHOEBE) | 2017-07-31 to 2018-10-30 | Phase 3 (E-switch-ic) | Capecitabine & Lapatinib | Superior PFS (primary endpoint) Median PFS: 12.5 vs 6.8 mo (HR 0.39, 95% CI 0.27-0.56) |
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
Targeted therapy
- Pyrotinib (Irene) 400 mg PO once per day on days 1 to 21
21-day cycles
References
- PHOEBE: Xu B, Yan M, Ma F, Hu X, Feng J, Ouyang Q, Tong Z, Li H, Zhang Q, Sun T, Wang X, Yin Y, Cheng Y, Li W, Gu Y, Chen Q, Liu J, Cheng J, Geng C, Qin S, Wang S, Lu J, Shen K, Liu Q, Wang X, Wang H, Luo T, Yang J, Wu Y, Yu Z, Zhu X, Chen C, Zou J; PHOEBE Investigators. Pyrotinib plus capecitabine versus lapatinib plus capecitabine for the treatment of HER2-positive metastatic breast cancer (PHOEBE): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2021 Mar;22(3):351-360. Epub 2021 Feb 11. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT03080805
Capecitabine & Trastuzumab (XH)
XH: Xeloda (Capecitabine) & Herceptin (Trastuzumab)
Regimen variant #1, 2000/6, with loading dose
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rugo et al. 2021 (SOPHIA) | 2015-2018 | Phase 3 (C) | 1a. Capecitabine & Margetuximab 1b. Eribulin & Margetuximab 1c. Gemcitabine & Margetuximab 1d. Vinorelbine & Margetuximab |
Seems to have inferior PFS |
Murthy et al. 2019 (HER2CLIMB) | 2016-2019 | Phase 3 (C) | XH & Tucatinib | Inferior OS |
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
Regimen variant #2, 2500/6, with loading dose
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bartsch et al. 2007 | 2004-2006 | Phase 2 | ||
Pivot et al. 2015 (CEREBEL) | 2009-2012 | Phase 3 (C) | Capecitabine & Lapatanib | Did not meet primary endpoint of CNS metastases as first site of relapse |
Urruticoechea et al. 2017 (PHEREXA) | 2010-2013 | Phase 3 (C) | XHP | Might have inferior PFS |
Yamamoto et al. 2022 (PRECIOUS) | 2015-2018 | Phase 3 (C) | 1a. THP (Docetaxel) 1b. THP (Paclitaxel) 1c. nab-Paclitaxel, Pertuzumab, Trastuzumab 1d. VHP 1e. EHP 1f. XHP 1g. GHP |
Might have inferior OS |
André et al. 2023 (DESTINY-Breast02) | 2018-09-06 to 2020-12-31 | Phase 3 (C) | T-DXd | Inferior PFS |
Note: the only difference between this and the next variant is the use of a loading dose of trastuzumab. The primary endpoint of CEREBEL was incidence of CNS as site of first relapse; this was very low in both arms, with no statistically significant difference.
Prior treatment criteria
- Bartsch et al. 2007: anthracycline and docetaxel or vinorelbine failure and prior trastuzumab exposure
- CEREBEL: prior anthracycline and/or taxanes
- PHEREXA: taxane
- PRECIOUS: History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this.
- DESTINY-Breast02: trastuzumab and a taxane
Chemotherapy
- Capecitabine (Xeloda) 1250 mg/m2 PO twice per day on days 1 to 14
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
Regimen variant #3, 2500/6, no loading dose
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2009 (GBG 26/BIG 3-05) | 2003 to not reported | Phase 3 (E-esc) | Capecitabine | Seems to have superior TTP (primary endpoint) Median TTP: 8.2 vs 5.6 mo (HR 0.69, 95% CI 0.48-0.97) |
Note: This was a continuation of trastuzumab so there is no loading dose.
Chemotherapy
- Capecitabine (Xeloda) 1250 mg/m2 PO twice per day on days 1 to 14
Targeted therapy
- Trastuzumab (Herceptin) 6 mg/kg IV once on day 1
21-day cycles
References
- Bartsch R, Wenzel C, Altorjai G, Pluschnig U, Rudas M, Mader RM, Gnant M, Zielinski CC, Steger GG. Capecitabine and trastuzumab in heavily pretreated metastatic breast cancer. J Clin Oncol. 2007 Sep 1;25(25):3853-8. Epub 2007 Aug 6. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- GBG 26/BIG 3-05: von Minckwitz G, du Bois A, Schmidt M, Maass N, Cufer T, de Jongh FE, Maartense E, Zielinski C, Kaufmann M, Bauer W, Baumann KH, Clemens MR, Duerr R, Uleer C, Andersson M, Stein RC, Nekljudova V, Loibl S. Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: a German Breast Group 26/Breast International Group 03-05 study. J Clin Oncol. 2009 Apr 20;27(12):1999-2006. Epub 2009 Mar 16. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00148876
- Update: von Minckwitz G, Schwedler K, Schmidt M, Barinoff J, Mundhenke C, Cufer T, Maartense E, de Jongh FE, Baumann KH, Bischoff J, Harbeck N, Lück HJ, Maass N, Zielinski C, Andersson M, Stein RC, Nekljudova V, Loibl S; GBG 26/BIG 03-05 study group and participating investigators. Trastuzumab beyond progression: overall survival analysis of the GBG 26/BIG 3-05 phase III study in HER2-positive breast cancer. Eur J Cancer. 2011 Oct;47(15):2273-81. Epub 2011 Jul 7. link to original article PubMed
- CEREBEL: Pivot X, Manikhas A, Żurawski B, Chmielowska E, Karaszewska B, Allerton R, Chan S, Fabi A, Bidoli P, Gori S, Ciruelos E, Dank M, Hornyak L, Margolin S, Nusch A, Parikh R, Nagi F, DeSilvio M, Santillana S, Swaby RF, Semiglazov V. CEREBEL (EGF111438): A phase III, randomized, open-label study of lapatinib plus capecitabine versus trastuzumab plus capecitabine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2015 May 10;33(14):1564-73. Epub 2015 Jan 20. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00820222
- PHEREXA: Urruticoechea A, Rizwanullah M, Im SA, Ruiz ACS, Láng I, Tomasello G, Douthwaite H, Badovinac Crnjevic T, Heeson S, Eng-Wong J, Muñoz M. Randomized phase III trial of trastuzumab plus capecitabine with or without pertuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who experienced disease progression during or after trastuzumab-based therapy. J Clin Oncol. 2017 Sep 10;35(26):3030-3038. Epub 2017 Apr 24. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01026142
- HER2CLIMB: Murthy RK, Loi S, Okines A, Paplomata E, Hamilton E, Hurvitz SA, Lin NU, Borges V, Abramson V, Anders C, Bedard PL, Oliveira M, Jakobsen E, Bachelot T, Shachar SS, Müller V, Braga S, Duhoux FP, Greil R, Cameron D, Carey LA, Curigliano G, Gelmon K, Hortobagyi G, Krop I, Loibl S, Pegram M, Slamon D, Palanca-Wessels MC, Walker L, Feng W, Winer EP. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. N Engl J Med. 2020 Feb 13;382(7):597-609. Epub 2019 Dec 11. Erratum in: N Engl J Med. 2020 Feb 6;382(6):586. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02614794
- Subgroup analysis: Lin NU, Borges V, Anders C, Murthy RK, Paplomata E, Hamilton E, Hurvitz S, Loi S, Okines A, Abramson V, Bedard PL, Oliveira M, Mueller V, Zelnak A, DiGiovanna MP, Bachelot T, Chien AJ, O'Regan R, Wardley A, Conlin A, Cameron D, Carey L, Curigliano G, Gelmon K, Loibl S, Mayor J, McGoldrick S, An X, Winer EP. Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial. J Clin Oncol. 2020 Aug 10;38(23):2610-2619. Epub 2020 May 29. link to original article link to PMC article PubMed
- Update: Curigliano G, Mueller V, Borges V, Hamilton E, Hurvitz S, Loi S, Murthy R, Okines A, Paplomata E, Cameron D, Carey LA, Gelmon K, Hortobagyi GN, Krop I, Loibl S, Pegram M, Slamon D, Ramos J, Feng W, Winer E. Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysis. Ann Oncol. 2022 Mar;33(3):321-329. Epub 2021 Dec 23. link to original article PubMed
- SOPHIA: Rugo HS, Im SA, Cardoso F, Cortés J, Curigliano G, Musolino A, Pegram MD, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Kaufman B, Yerushalmi R, Fasching PA, Nordstrom JL, Bonvini E, Koenig S, Edlich S, Hong S, Rock EP, Gradishar WJ; SOPHIA Study Group. Efficacy of Margetuximab vs Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Apr 1;7(4):573-584. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT02492711
- Update: Rugo HS, Im SA, Cardoso F, Cortes J, Curigliano G, Musolino A, Pegram MD, Bachelot T, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Schwartz GN, Pluard TJ, Ricci F, Gwin WR 3rd, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Gal-Yam EN, Yerushalmi R, Fasching PA, Kaufman PA, Ashley EJ, Perez-Olle R, Hong S, Rosales MK, Gradishar WJ; SOPHIA Study Group. Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial. J Clin Oncol. 2023 Jan 10;41(2):198-205. Epub 2022 Nov 4. link to original article linnk to PMC article PubMed
- PRECIOUS: Yamamoto Y, Iwata H, Taira N, Masuda N, Takahashi M, Yoshinami T, Ueno T, Toyama T, Yamanaka T, Takano T, Kashiwaba M, Tsugawa K, Hasegawa Y, Tamura K, Tada H, Hara F, Fujisawa T, Niikura N, Saji S, Morita S, Toi M, Ohno S. Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS). Cancer Sci. 2022 Sep;113(9):3169-3179. Epub 2022 Jul 23. link to original article link to PMC article dosing details in supplement have been reviewed by our editors PubMed UMIN000018202
- DESTINY-Breast02: André F, Hee Park Y, Kim SB, Takano T, Im SA, Borges G, Lima JP, Aksoy S, Gavila Gregori J, De Laurentiis M, Bianchini G, Roylance R, Miyoshi Y, Armstrong A, Sinha R, Ruiz Borrego M, Lim E, Ettl J, Yerushalmi R, Zagouri F, Duhoux FP, Fehm T, Gambhire D, Cathcart J, Wu C, Chu C, Egorov A, Krop I. Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2023 May 27;401(10390):1773-1785. Epub 2023 Apr 20. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT03523585
- PRO analysis: Fehm T, Cottone F, Dunton K, André F, Krop I, Park YH, De Laurentiis M, Miyoshi Y, Armstrong A, Borrego MR, Yerushalmi R, Duhoux FP, Takano T, Lu W, Egorov A, Kim SB. Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): patient-reported outcomes from a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2024 May;25(5):614-625. link to original article PubMed
Capecitabine & Trastuzumab (XH) & Tucatinib
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Murthy et al. 2019 (HER2CLIMB) | 2016-2019 | Phase 3 (E-RT-esc) | XH | Superior PFS1 (primary endpoint) Median PFS: 7.6 vs 4.9 mo (HR 0.57, 95% CI 0.47-0.70) Superior OS1 (secondary endpoint) Median OS: 24.7 vs 19.2 mo (HR 0.73, 95% CI 0.59-0.90) |
1Reported efficacy is based on the 2021 update.
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
Targeted therapy
- Tucatinib (Tukysa) 300 mg PO twice per day on days 1 to 21
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
References
- HER2CLIMB: Murthy RK, Loi S, Okines A, Paplomata E, Hamilton E, Hurvitz SA, Lin NU, Borges V, Abramson V, Anders C, Bedard PL, Oliveira M, Jakobsen E, Bachelot T, Shachar SS, Müller V, Braga S, Duhoux FP, Greil R, Cameron D, Carey LA, Curigliano G, Gelmon K, Hortobagyi G, Krop I, Loibl S, Pegram M, Slamon D, Palanca-Wessels MC, Walker L, Feng W, Winer EP. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. N Engl J Med. 2020 Feb 13;382(7):597-609. Epub 2019 Dec 11. Erratum in: N Engl J Med. 2020 Feb 6;382(6):586. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02614794
- Subgroup analysis: Lin NU, Borges V, Anders C, Murthy RK, Paplomata E, Hamilton E, Hurvitz S, Loi S, Okines A, Abramson V, Bedard PL, Oliveira M, Mueller V, Zelnak A, DiGiovanna MP, Bachelot T, Chien AJ, O'Regan R, Wardley A, Conlin A, Cameron D, Carey L, Curigliano G, Gelmon K, Loibl S, Mayor J, McGoldrick S, An X, Winer EP. Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial. J Clin Oncol. 2020 Aug 10;38(23):2610-2619. Epub 2020 May 29. link to original article link to PMC article PubMed
- Update: Curigliano G, Mueller V, Borges V, Hamilton E, Hurvitz S, Loi S, Murthy R, Okines A, Paplomata E, Cameron D, Carey LA, Gelmon K, Hortobagyi GN, Krop I, Loibl S, Pegram M, Slamon D, Ramos J, Feng W, Winer E. Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysis. Ann Oncol. 2022 Mar;33(3):321-329. Epub 2021 Dec 23. link to original article PubMed
Docetaxel & Trastuzumab (TH)
TH: Taxotere (Docetaxel) & Herceptin (Trastuzumab)
Regimen variant #1, 60 mg/m2 docetaxel
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yamamoto et al. 2022 (PRECIOUS) | 2015-2018 | Phase 3 (C) | 1a. THP (Docetaxel) 1b. THP (Paclitaxel) 1c. nab-Paclitaxel, Pertuzumab, Trastuzumab 1d. VHP 1e. EHP 1f. XHP 1g. GHP |
Might have inferior OS |
Prior treatment criteria
- History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this.
Chemotherapy
- Docetaxel (Taxotere) 60 mg/m2 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
Regimen variant #2, 75 mg/m2 docetaxel
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yamamoto et al. 2022 (PRECIOUS) | 2015-2018 | Phase 3 (C) | 1a. THP (Docetaxel) 1b. THP (Paclitaxel) 1c. nab-Paclitaxel, Pertuzumab, Trastuzumab 1d. VHP 1e. EHP 1f. XHP 1g. GHP |
Might have inferior OS |
Prior treatment criteria
- History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this.
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
References
- PRECIOUS: Yamamoto Y, Iwata H, Taira N, Masuda N, Takahashi M, Yoshinami T, Ueno T, Toyama T, Yamanaka T, Takano T, Kashiwaba M, Tsugawa K, Hasegawa Y, Tamura K, Tada H, Hara F, Fujisawa T, Niikura N, Saji S, Morita S, Toi M, Ohno S. Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS). Cancer Sci. 2022 Sep;113(9):3169-3179. Epub 2022 Jul 23. link to original article link to PMC article dosing details in supplement have been reviewed by our editors PubMed UMIN000018202
EHP
EHP: Eribulin, Herceptin (Trastuzumab), Pertuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yamamoto et al. 2022 (PRECIOUS) | 2015-2018 | Phase 3 (E-esc) | 1a. TH (Docetaxel) 1b. TH (Paclitaxel) 1c. nab-Paclitaxel & Trastuzumab 1d. VH 1e. EH 1f. XH 1g. GH |
Might have superior OS1 (secondary endpoint) Median OS: 28.8 vs 23.4 mo (HR 0.71, 95% CI NA-1.03) Seems to have superior PFS (primary endpoint) Median PFS: 5.3 vs 4.2 mo (sHR 0.76, 95% CI NA-0.97) |
1Results are based on a one-sided statistical analysis.
Prior treatment criteria
- PRECIOUS: History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this.
Chemotherapy
- Eribulin (Halaven) 1.4 mg/m2 IV once per day on days 1 & 8
Targeted therapy
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycle 2 onwards: 420 mg IV once on day 1
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
References
- PRECIOUS: Yamamoto Y, Iwata H, Taira N, Masuda N, Takahashi M, Yoshinami T, Ueno T, Toyama T, Yamanaka T, Takano T, Kashiwaba M, Tsugawa K, Hasegawa Y, Tamura K, Tada H, Hara F, Fujisawa T, Niikura N, Saji S, Morita S, Toi M, Ohno S. Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS). Cancer Sci. 2022 Sep;113(9):3169-3179. Epub 2022 Jul 23. link to original article link to PMC article dosing details in supplement have been reviewed by our editors PubMed UMIN000018202
Eribulin & Margetuximab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rugo et al. 2021 (SOPHIA) | 2015-2018 | Phase 3 (E-RT-switch-ic) | 1a. Eribulin & Trastuzumab 1b. Gemcitabine & Trastuzumab 1c. VH 1d. XH |
Seems to have superior PFS (primary endpoint) Median PFS: 6 vs 5 mo (HR 0.76, 95% CI 0.59-0.98) Did not meet secondary endpoint of OS1 Median OS: 21.6 vs 21.9 mo (HR 0.95, 95% CI 0.77-1.17) |
1Reported efficacy is based on the 2022 update.
Chemotherapy
- Eribulin (Halaven) 1.4 mg/m2 IV once per day on days 1 & 8
Targeted therapy
- Margetuximab (Margenza) 15 mg/kg IV over 120 minutes once on day 1
21-day cycles
References
- SOPHIA: Rugo HS, Im SA, Cardoso F, Cortés J, Curigliano G, Musolino A, Pegram MD, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Kaufman B, Yerushalmi R, Fasching PA, Nordstrom JL, Bonvini E, Koenig S, Edlich S, Hong S, Rock EP, Gradishar WJ; SOPHIA Study Group. Efficacy of Margetuximab vs Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Apr 1;7(4):573-584. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT02492711
- Update: Rugo HS, Im SA, Cardoso F, Cortes J, Curigliano G, Musolino A, Pegram MD, Bachelot T, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Schwartz GN, Pluard TJ, Ricci F, Gwin WR 3rd, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Gal-Yam EN, Yerushalmi R, Fasching PA, Kaufman PA, Ashley EJ, Perez-Olle R, Hong S, Rosales MK, Gradishar WJ; SOPHIA Study Group. Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial. J Clin Oncol. 2023 Jan 10;41(2):198-205. Epub 2022 Nov 4. link to original article link to PMC article link to PMC article PubMed
Eribulin & Trastuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rugo et al. 2021 (SOPHIA) | 2015-2018 | Phase 3 (C) | 1a. Capecitabine & Margetuximab 1b. Eribulin & Margetuximab 1c. Gemcitabine & Margetuximab 1d. Vinorelbine & Margetuximab |
Seems to have inferior PFS |
Yamamoto et al. 2022 (PRECIOUS) | 2015-2018 | Phase 3 (C) | 1a. THP (Docetaxel) 1b. THP (Paclitaxel) 1c. nab-Paclitaxel, Pertuzumab, Trastuzumab 1d. VHP 1e. EHP 1f. XHP 1g. GHP |
Might have inferior OS |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Prior treatment criteria
- PRECIOUS: History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this.
Chemotherapy
- Eribulin (Halaven) 1.4 mg/m2 IV once per day on days 1 & 8
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
References
- SOPHIA: Rugo HS, Im SA, Cardoso F, Cortés J, Curigliano G, Musolino A, Pegram MD, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Kaufman B, Yerushalmi R, Fasching PA, Nordstrom JL, Bonvini E, Koenig S, Edlich S, Hong S, Rock EP, Gradishar WJ; SOPHIA Study Group. Efficacy of Margetuximab vs Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Apr 1;7(4):573-584. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT02492711
- Update: Rugo HS, Im SA, Cardoso F, Cortes J, Curigliano G, Musolino A, Pegram MD, Bachelot T, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Schwartz GN, Pluard TJ, Ricci F, Gwin WR 3rd, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Gal-Yam EN, Yerushalmi R, Fasching PA, Kaufman PA, Ashley EJ, Perez-Olle R, Hong S, Rosales MK, Gradishar WJ; SOPHIA Study Group. Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial. J Clin Oncol. 2023 Jan 10;41(2):198-205. Epub 2022 Nov 4. link to original article link to PMC article PubMed
- PRECIOUS: Yamamoto Y, Iwata H, Taira N, Masuda N, Takahashi M, Yoshinami T, Ueno T, Toyama T, Yamanaka T, Takano T, Kashiwaba M, Tsugawa K, Hasegawa Y, Tamura K, Tada H, Hara F, Fujisawa T, Niikura N, Saji S, Morita S, Toi M, Ohno S. Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS). Cancer Sci. 2022 Sep;113(9):3169-3179. Epub 2022 Jul 23. link to original article link to PMC article dosing details in supplement have been reviewed by our editors PubMed UMIN000018202
Gemcitabine & Margetuximab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rugo et al. 2021 (SOPHIA) | 2015-2018 | Phase 3 (E-RT-switch-ic) | 1a. Eribulin & Trastuzumab 1b. Gemcitabine & Trastuzumab 1c. VH 1d. XH |
Seems to have superior PFS (primary endpoint) Median PFS: 6 vs 5 mo (HR 0.76, 95% CI 0.59-0.98) Did not meet secondary endpoint of OS1 Median OS: 21.6 vs 21.9 mo (HR 0.95, 95% CI 0.77-1.17) |
1Reported efficacy is based on the 2022 update.
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
Targeted therapy
- Margetuximab (Margenza) 15 mg/kg IV over 120 minutes once on day 1
21-day cycles
References
- SOPHIA: Rugo HS, Im SA, Cardoso F, Cortés J, Curigliano G, Musolino A, Pegram MD, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Kaufman B, Yerushalmi R, Fasching PA, Nordstrom JL, Bonvini E, Koenig S, Edlich S, Hong S, Rock EP, Gradishar WJ; SOPHIA Study Group. Efficacy of Margetuximab vs Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Apr 1;7(4):573-584. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT02492711
- Update: Rugo HS, Im SA, Cardoso F, Cortes J, Curigliano G, Musolino A, Pegram MD, Bachelot T, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Schwartz GN, Pluard TJ, Ricci F, Gwin WR 3rd, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Gal-Yam EN, Yerushalmi R, Fasching PA, Kaufman PA, Ashley EJ, Perez-Olle R, Hong S, Rosales MK, Gradishar WJ; SOPHIA Study Group. Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial. J Clin Oncol. 2023 Jan 10;41(2):198-205. Epub 2022 Nov 4. link to original article link to PMC article PubMed
Gemcitabine & Trastuzumab
Regimen variant #1, 1000/q3wk trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rugo et al. 2021 (SOPHIA) | 2015-2018 | Phase 3 (C) | 1a. Capecitabine & Margetuximab 1b. Eribulin & Margetuximab 1c. Gemcitabine & Margetuximab 1d. Vinorelbine & Margetuximab |
Seems to have inferior PFS |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
Regimen variant #2, 1200/q3wk trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yamamoto et al. 2022 (PRECIOUS) | 2015-2018 | Phase 3 (C) | 1a. THP (Docetaxel) 1b. THP (Paclitaxel) 1c. nab-Paclitaxel, Pertuzumab, Trastuzumab 1d. VHP 1e. EHP 1f. XHP 1g. GHP |
Might have inferior OS |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Prior treatment criteria
- PRECIOUS: History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this.
Chemotherapy
- Gemcitabine (Gemzar) 1200 mg/m2 IV once per day on days 1 & 8
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
Regimen variant #3, weekly trastuzumab
Study | Dates of enrollment | Evidence |
---|---|---|
O'Shaughnessy et al. 2004 | 1999-04 to 2001-07 | Phase 2 |
Chemotherapy
- Gemcitabine (Gemzar) 1200 mg/m2 IV once per day on days 1 & 8
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycle 2 onwards: 2 mg/kg IV once per day on days 1, 8, 15
21-day cycles
References
- O'Shaughnessy JA, Vukelja S, Marsland T, Kimmel G, Ratnam S, Pippen JE. Phase II study of trastuzumab plus gemcitabine in chemotherapy-pretreated patients with metastatic breast cancer. Clin Breast Cancer. 2004 Jun;5(2):142-7. link to original article dosing details in abstract have been reviewed by our editors PubMed
- SOPHIA: Rugo HS, Im SA, Cardoso F, Cortés J, Curigliano G, Musolino A, Pegram MD, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Kaufman B, Yerushalmi R, Fasching PA, Nordstrom JL, Bonvini E, Koenig S, Edlich S, Hong S, Rock EP, Gradishar WJ; SOPHIA Study Group. Efficacy of Margetuximab vs Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Apr 1;7(4):573-584. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT02492711
- Update: Rugo HS, Im SA, Cardoso F, Cortes J, Curigliano G, Musolino A, Pegram MD, Bachelot T, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Schwartz GN, Pluard TJ, Ricci F, Gwin WR 3rd, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Gal-Yam EN, Yerushalmi R, Fasching PA, Kaufman PA, Ashley EJ, Perez-Olle R, Hong S, Rosales MK, Gradishar WJ; SOPHIA Study Group. Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial. J Clin Oncol. 2023 Jan 10;41(2):198-205. Epub 2022 Nov 4. link to original article link to PMC article PubMed
- PRECIOUS: Yamamoto Y, Iwata H, Taira N, Masuda N, Takahashi M, Yoshinami T, Ueno T, Toyama T, Yamanaka T, Takano T, Kashiwaba M, Tsugawa K, Hasegawa Y, Tamura K, Tada H, Hara F, Fujisawa T, Niikura N, Saji S, Morita S, Toi M, Ohno S. Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS). Cancer Sci. 2022 Sep;113(9):3169-3179. Epub 2022 Jul 23. link to original article link to PMC article dosing details in supplement have been reviewed by our editors PubMed UMIN000018202
GHP
GHP: Gemcitabine, Herceptin (Trastuzumab), Pertuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yamamoto et al. 2022 (PRECIOUS) | 2015-2018 | Phase 3 (E-esc) | 1a. TH (Docetaxel) 1b. TH (Paclitaxel) 1c. nab-Paclitaxel & Trastuzumab 1d. VH 1e. EH 1f. XH 1g. GH |
Might have superior OS1 (secondary endpoint) Median OS: 28.8 vs 23.4 mo (HR 0.71, 95% CI NA-1.03) Seems to have superior PFS (primary endpoint) Median PFS: 5.3 vs 4.2 mo (sHR 0.76, 95% CI NA-0.97) |
1Results are based on a one-sided statistical analysis.
Prior treatment criteria
- PRECIOUS: History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this.
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
Targeted therapy
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycle 2 onwards: 420 mg IV once on day 1
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
References
- PRECIOUS: Yamamoto Y, Iwata H, Taira N, Masuda N, Takahashi M, Yoshinami T, Ueno T, Toyama T, Yamanaka T, Takano T, Kashiwaba M, Tsugawa K, Hasegawa Y, Tamura K, Tada H, Hara F, Fujisawa T, Niikura N, Saji S, Morita S, Toi M, Ohno S. Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS). Cancer Sci. 2022 Sep;113(9):3169-3179. Epub 2022 Jul 23. link to original article link to PMC article dosing details in supplement have been reviewed by our editors PubMed UMIN000018202
Lapatinib & Trastuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Blackwell et al. 2010 (EGF104900) | 2005-11 to 2006-11 | Phase 3 (E-esc) | Lapatinib | Superior PFS1 (primary endpoint) Median PFS: 11.1 vs 8.1 weeks (HR 0.74, 95% CI 0.58-0.94) Seems to have superior OS1 (secondary endpoint) Median OS: 14 vs 9.5 mo (HR 0.74, 95% CI 0.57-0.97) |
1Reported efficacy is based on the 2012 update.
Targeted therapy
- Lapatinib (Tykerb) 1000 mg PO once per day on days 1 to 7
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1,
- Cycle 2 onwards: 2 mg/kg IV once on day 1
7-day cycles
References
- EGF104900: Blackwell KL, Burstein HJ, Storniolo AM, Rugo H, Sledge G, Koehler M, Ellis C, Casey M, Vukelja S, Bischoff J, Baselga J, O'Shaughnessy J. Randomized study of Lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol. 2010 Mar 1;28(7):1124-30. Epub 2010 Feb 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00320385
- Update: Blackwell KL, Burstein HJ, Storniolo AM, Rugo HS, Sledge G, Aktan G, Ellis C, Florance A, Vukelja S, Bischoff J, Baselga J, O'Shaughnessy J. Overall survival benefit with lapatinib in combination with trastuzumab for patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: final results from the EGF104900 Study. J Clin Oncol. 2012 Jul 20;30(21):2585-92. Epub 2012 Jun 11. link to original article PubMed
Paclitaxel & Trastuzumab (TH)
TH: Taxol (Paclitaxel), Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yamamoto et al. 2022 (PRECIOUS) | 2015-2018 | Phase 3 (C) | 1a. THP (Docetaxel) 1b. THP (Paclitaxel) 1c. nab-Paclitaxel, Pertuzumab, Trastuzumab 1d. VHP 1e. EHP 1f. XHP 1g. GHP |
Might have inferior OS |
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
References
- PRECIOUS: Yamamoto Y, Iwata H, Taira N, Masuda N, Takahashi M, Yoshinami T, Ueno T, Toyama T, Yamanaka T, Takano T, Kashiwaba M, Tsugawa K, Hasegawa Y, Tamura K, Tada H, Hara F, Fujisawa T, Niikura N, Saji S, Morita S, Toi M, Ohno S. Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS). Cancer Sci. 2022 Sep;113(9):3169-3179. Epub 2022 Jul 23. link to original article link to PMC article dosing details in supplement have been reviewed by our editors PubMed UMIN000018202
Paclitaxel, Pertuzumab, Trastuzumab emtansine
Regimen variant #1, q3wk T-DM1
Study | Dates of enrollment | Evidence |
---|---|---|
Krop et al. 2016 (TDM4652g) | 2009 to not reported | Phase 1b/2a |
Note: this is the MTD.
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycle 2 onwards: 420 mg IV once on day 1
Antibody-drug conjugate therapy
- Trastuzumab emtansine (Kadcyla) 3.6 mg/kg IV once on day 1
21-day cycles
Regimen variant #2, weekly T-DM1
Study | Dates of enrollment | Evidence |
---|---|---|
Krop et al. 2016 (TDM4652g) | 2009 to not reported | Phase 1b/2a |
Note: this is the MTD.
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycle 2 onwards: 420 mg IV once on day 1
Antibody-drug conjugate therapy
- Trastuzumab emtansine (Kadcyla) 2.4 mg/kg IV once per day on days 1, 8, 15
21-day cycles
References
- TDM4652g: Krop IE, Modi S, LoRusso PM, Pegram M, Guardino E, Althaus B, Lu D, Strasak A, Elias A. Phase 1b/2a study of trastuzumab emtansine (T-DM1), paclitaxel, and pertuzumab in HER2-positive metastatic breast cancer. Breast Cancer Res. 2016 Mar 15;18(1):34. link to original article link to PMC article dosing details in abstract have been reviewed by our editors PubMed
nab-Paclitaxel & Trastuzumab
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yamamoto et al. 2022 (PRECIOUS) | 2015-2018 | Phase 3 (C) | 1a. THP (Docetaxel) 1b. THP (Paclitaxel) 1c. nab-Paclitaxel, Pertuzumab, Trastuzumab 1d. VHP 1e. EHP 1f. XHP 1g. GHP |
Might have inferior OS |
Chemotherapy
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 220 mg/m2 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yamamoto et al. 2022 (PRECIOUS) | 2015-2018 | Phase 3 (C) | 1a. THP (Docetaxel) 1b. THP (Paclitaxel) 1c. nab-Paclitaxel, Pertuzumab, Trastuzumab 1d. VHP 1e. EHP 1f. XHP 1g. GHP |
Might have inferior OS |
Chemotherapy
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 260 mg/m2 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
References
- PRECIOUS: Yamamoto Y, Iwata H, Taira N, Masuda N, Takahashi M, Yoshinami T, Ueno T, Toyama T, Yamanaka T, Takano T, Kashiwaba M, Tsugawa K, Hasegawa Y, Tamura K, Tada H, Hara F, Fujisawa T, Niikura N, Saji S, Morita S, Toi M, Ohno S. Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS). Cancer Sci. 2022 Sep;113(9):3169-3179. Epub 2022 Jul 23. link to original article link to PMC article dosing details in supplement have been reviewed by our editors PubMed UMIN000018202
nab-Paclitaxel, Pertuzumab, Trastuzumab
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yamamoto et al. 2022 (PRECIOUS) | 2015-2018 | Phase 3 (E-esc) | 1a. TH (Docetaxel) 1b. TH (Paclitaxel) 1c. nab-Paclitaxel & Trastuzumab 1d. VH 1e. EH 1f. XH 1g. GH |
Might have superior OS1 (secondary endpoint) Median OS: 28.8 vs 23.4 mo (HR 0.71, 95% CI NA-1.03) Seems to have superior PFS (primary endpoint) Median PFS: 5.3 vs 4.2 mo (sHR 0.76, 95% CI NA-0.97) |
1Results are based on a one-sided statistical analysis.
Prior treatment criteria
- PRECIOUS: History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this.
Chemotherapy
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 220 mg/m2 IV once on day 1
Targeted therapy
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycle 2 onwards: 420 mg IV once on day 1
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yamamoto et al. 2022 (PRECIOUS) | 2015-2018 | Phase 3 (E-esc) | 1a. TH (Docetaxel) 1b. TH (Paclitaxel) 1c. nab-Paclitaxel & Trastuzumab 1d. VH 1e. EH 1f. XH 1g. GH |
Might have superior OS1 (secondary endpoint) Median OS: 28.8 vs 23.4 mo (HR 0.71, 95% CI NA-1.03) Seems to have superior PFS (primary endpoint) Median PFS: 5.3 vs 4.2 mo (sHR 0.76, 95% CI NA-0.97) |
1Results are based on a one-sided statistical analysis.
Prior treatment criteria
- PRECIOUS: History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this.
Chemotherapy
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 260 mg/m2 IV once on day 1
Targeted therapy
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycle 2 onwards: 420 mg IV once on day 1
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
References
- PRECIOUS: Yamamoto Y, Iwata H, Taira N, Masuda N, Takahashi M, Yoshinami T, Ueno T, Toyama T, Yamanaka T, Takano T, Kashiwaba M, Tsugawa K, Hasegawa Y, Tamura K, Tada H, Hara F, Fujisawa T, Niikura N, Saji S, Morita S, Toi M, Ohno S. Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS). Cancer Sci. 2022 Sep;113(9):3169-3179. Epub 2022 Jul 23. link to original article link to PMC article dosing details in supplement have been reviewed by our editors PubMed UMIN000018202
Pertuzumab & Trastuzumab
Regimen variant #1, q3wk trastuzumab
Study | Dates of enrollment | Evidence |
---|---|---|
Baselga et al. 2010 (NCI-P6660) | 2005 to not reported | Phase 2 |
Targeted therapy
- Pertuzumab (Perjeta) as follows, given second:
- Cycle 1: 840 mg IV once on day 2
- Cycle 2 onwards: 420 mg IV once on day 1
- Trastuzumab (Herceptin) as follows:
- Loading dose: 8 mg/kg IV once on day -28 (that is, 28 days before the start of cycle 1)
- Cycle 1 onwards: 6 mg/kg IV once on day 1, given first
21-day cycle for 8 cycles Treatment can be continued if there is no progressive disease.
Regimen variant #2, weekly trastuzumab
Study | Dates of enrollment | Evidence |
---|---|---|
Baselga et al. 2010 (NCI-P6660) | 2005 to not reported | Phase 2 |
Targeted therapy
- Pertuzumab (Perjeta) given second as follows:
- Cycle 1: 840 mg IV once on day 2
- Cycles 2 to 8: 420 mg IV once on day 1
- Trastuzumab (Herceptin) given first as follows:
- Cycle 0: 4 mg/kg IV once on day -28 (that is, 28 days before the start of cycle 1)
- Cycles 1 to 8: 2 mg/kg IV once per day on days 1, 8, 15
21-day cycle for 8 cycles; treatment can be continued if there is no progressive disease
References
- NCI-P6660: Baselga J, Gelmon KA, Verma S, Wardley A, Conte P, Miles D, Bianchi G, Cortes J, McNally VA, Ross GA, Fumoleau P, Gianni L. Phase II trial of pertuzumab and trastuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer that progressed during prior trastuzumab therapy. J Clin Oncol. 2010 Mar 1;28(7):1138-44. Epub 2010 Feb 1. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00301899
THP (Docetaxel)
THP: Taxotere (Docetaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yamamoto et al. 2022 (PRECIOUS) | 2015-2018 | Phase 3 (E-esc) | 1a. TH (Docetaxel) 1b. TH (Paclitaxel) 1c. nab-Paclitaxel & Trastuzumab 1d. VH 1e. EH 1f. XH 1g. GH |
Might have superior OS1 (secondary endpoint) Median OS: 28.8 vs 23.4 mo (HR 0.71, 95% CI NA-1.03) Seems to have superior PFS (primary endpoint) Median PFS: 5.3 vs 4.2 mo (sHR 0.76, 95% CI NA-0.97) |
1Results are based on a one-sided statistical analysis.
Prior treatment criteria
- PRECIOUS: History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this.
Chemotherapy
- Docetaxel (Taxotere) 60 mg/m2 IV once on day 1
Targeted therapy
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycle 2 onwards: 420 mg IV once on day 1
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yamamoto et al. 2022 (PRECIOUS) | 2015-2018 | Phase 3 (E-esc) | 1a. TH (Docetaxel) 1b. TH (Paclitaxel) 1c. nab-Paclitaxel & Trastuzumab 1d. VH 1e. EH 1f. XH 1g. GH |
Might have superior OS1 (secondary endpoint) Median OS: 28.8 vs 23.4 mo (HR 0.71, 95% CI NA-1.03) Seems to have superior PFS (primary endpoint) Median PFS: 5.3 vs 4.2 mo (sHR 0.76, 95% CI NA-0.97) |
1Results are based on a one-sided statistical analysis.
Prior treatment criteria
- PRECIOUS: History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this.
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycle 2 onwards: 420 mg IV once on day 1
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
References
- PRECIOUS: Yamamoto Y, Iwata H, Taira N, Masuda N, Takahashi M, Yoshinami T, Ueno T, Toyama T, Yamanaka T, Takano T, Kashiwaba M, Tsugawa K, Hasegawa Y, Tamura K, Tada H, Hara F, Fujisawa T, Niikura N, Saji S, Morita S, Toi M, Ohno S. Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS). Cancer Sci. 2022 Sep;113(9):3169-3179. Epub 2022 Jul 23. link to original article link to PMC article dosing details in supplement have been reviewed by our editors PubMed UMIN000018202
THP (Paclitaxel)
THP: Taxol (Paclitaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yamamoto et al. 2022 (PRECIOUS) | 2015-2018 | Phase 3 (E-esc) | 1a. TH (Docetaxel) 1b. TH (Paclitaxel) 1c. nab-Paclitaxel & Trastuzumab 1d. VH 1e. EH 1f. XH 1g. GH |
Might have superior OS1 (secondary endpoint) Median OS: 28.8 vs 23.4 mo (HR 0.71, 95% CI NA-1.03) Seems to have superior PFS (primary endpoint) Median PFS: 5.3 vs 4.2 mo (sHR 0.76, 95% CI NA-0.97) |
1Results are based on a one-sided statistical analysis.
Prior treatment criteria
- PRECIOUS: History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this.
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycle 2 onwards: 420 mg IV once on day 1
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
References
- PRECIOUS: Yamamoto Y, Iwata H, Taira N, Masuda N, Takahashi M, Yoshinami T, Ueno T, Toyama T, Yamanaka T, Takano T, Kashiwaba M, Tsugawa K, Hasegawa Y, Tamura K, Tada H, Hara F, Fujisawa T, Niikura N, Saji S, Morita S, Toi M, Ohno S. Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS). Cancer Sci. 2022 Sep;113(9):3169-3179. Epub 2022 Jul 23. link to original article link to PMC article dosing details in supplement have been reviewed by our editors PubMed UMIN000018202
Trastuzumab monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Cobleigh et al. 1999 | 1995-04 to 1996-09 | Phase 2 (RT) |
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV over 90 minutes once on day 1
- Cycle 2 onwards: 2 mg/kg IV over 30 minutes once on day 1
7-day cycles
References
- Cobleigh MA, Vogel CL, Tripathy D, Robert NJ, Scholl S, Fehrenbacher L, Wolter JM, Paton V, Shak S, Lieberman G, Slamon DJ. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol. 1999 Sep;17(9):2639-48. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Trastuzumab deruxtecan monotherapy
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Modi et al. 2019 (DESTINY-Breast01) | 2017-2018 | Phase 2 (RT) | ||
Cortés et al. 2022 (DESTINY-Breast03) | 2018-2020 | Phase 3 (E-RT-switch-ic) | T-DM1 | Superior PFS (primary endpoint) PFS12: 75.8% vs 34.1% (HR 0.28, 95% CI 0.22-0.37) Superior OS1 (secondary endpoint) Median OS: NYR vs NYR (HR 0.64, 95% CI 0.47-0.87) |
André et al. 2023 (DESTINY-Breast02) | 2018-09-06 to 2020-12-31 | Phase 3 (E-switch-ooc) | Investigator's choice of: 1a. Capecitabine & Lapatinib 1b. XH |
Superior PFS (primary endpoint) Median PFS: 17.8 vs 6.9 mo (HR 0.36, 95% CI 0.28-0.45) |
1Reported efficacy is based on the 2022 update.
Prior treatment criteria
- DESTINY-Breast01 & DESTINY-Breast02: Refractory to trastuzumab emtansine
- DESTINY-Breast03: Trastuzumab and taxane
Antibody-drug conjugate therapy
- Trastuzumab deruxtecan (Enhertu) 5.4 mg/kg IV once on day 1
21-day cycles
References
- DESTINY-Breast01: Modi S, Saura C, Yamashita T, Park YH, Kim SB, Tamura K, Andre F, Iwata H, Ito Y, Tsurutani J, Sohn J, Denduluri N, Perrin C, Aogi K, Tokunaga E, Im SA, Lee KS, Hurvitz SA, Cortes J, Lee C, Chen S, Zhang L, Shahidi J, Yver A, Krop I; DESTINY-Breast01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. N Engl J Med. 2020 Feb 13;382(7):610-621. Epub 2019 Dec 11. link to original article dosing details in abstract have been reviewed by our editors link to PMC article PubMed NCT03248492
- Update: Saura C, Modi S, Krop I, Park YH, Kim SB, Tamura K, Iwata H, Tsurutani J, Sohn J, Mathias E, Liu Y, Cathcart J, Singh J, Yamashita T. Trastuzumab deruxtecan in previously treated patients with HER2-positive metastatic breast cancer: updated survival results from a phase II trial (DESTINY-Breast01). Ann Oncol. 2024 Mar;35(3):302-307. Epub 2023 Dec 11. link to original article PubMed
- DESTINY-Breast03: Cortés J, Kim SB, Chung WP, Im SA, Park YH, Hegg R, Kim MH, Tseng LM, Petry V, Chung CF, Iwata H, Hamilton E, Curigliano G, Xu B, Huang CS, Kim JH, Chiu JWY, Pedrini JL, Lee C, Liu Y, Cathcart J, Bako E, Verma S, Hurvitz SA; DESTINY-Breast03 Trial Investigators. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med. 2022 Mar 24;386(12):1143-1154. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT03529110
- Update: Hurvitz SA, Hegg R, Chung WP, Im SA, Jacot W, Ganju V, Chiu JWY, Xu B, Hamilton E, Madhusudan S, Iwata H, Altintas S, Henning JW, Curigliano G, Perez-Garcia JM, Kim SB, Petry V, Huang CS, Li W, Frenel JS, Antolin S, Yeo W, Bianchini G, Loi S, Tsurutani J, Egorov A, Liu Y, Cathcart J, Ashfaque S, Cortés J. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. Lancet. 2023 Jan 14;401(10371):105-117. Epub 2022 Dec 7. link to original article PubMed
- PRO analysis: Curigliano G, Dunton K, Rosenlund M, Janek M, Cathcart J, Liu Y, Fasching PA, Iwata H. Patient-reported outcomes and hospitalization data in patients with HER2-positive metastatic breast cancer receiving trastuzumab deruxtecan or trastuzumab emtansine in the phase III DESTINY-Breast03 study. Ann Oncol. 2023 Jul;34(7):569-577. Epub 2023 May 12. link to original article PubMed
- Subgroup analysis: Hurvitz SA, Kim SB, Chung WP, Im SA, Park YH, Hegg R, Kim MH, Tseng LM, Petry V, Chung CF, Iwata H, Hamilton E, Curigliano G, Xu B, Egorov A, Liu Y, Cathcart J, Bako E, Tecson K, Verma S, Cortés J. Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer patients with brain metastases from the randomized DESTINY-Breast03 trial. ESMO Open. 2024 May;9(5):102924. Epub 2024 Apr 24. link to original article link to PMC article PubMed
- DESTINY-Breast02: André F, Hee Park Y, Kim SB, Takano T, Im SA, Borges G, Lima JP, Aksoy S, Gavila Gregori J, De Laurentiis M, Bianchini G, Roylance R, Miyoshi Y, Armstrong A, Sinha R, Ruiz Borrego M, Lim E, Ettl J, Yerushalmi R, Zagouri F, Duhoux FP, Fehm T, Gambhire D, Cathcart J, Wu C, Chu C, Egorov A, Krop I. Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2023 May 27;401(10390):1773-1785. Epub 2023 Apr 20. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT03523585
- PRO analysis: Fehm T, Cottone F, Dunton K, André F, Krop I, Park YH, De Laurentiis M, Miyoshi Y, Armstrong A, Borrego MR, Yerushalmi R, Duhoux FP, Takano T, Lu W, Egorov A, Kim SB. Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): patient-reported outcomes from a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2024 May;25(5):614-625. link to original article PubMed
Trastuzumab emtansine monotherapy
T-DM1: Trastuzumab-DM1 (Trastuzumab emtansine)
Example orders
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Verma et al. 2012 (EMILIA) | 2009-2011 | Phase 3 (E-RT-switch-ooc) | Capecitabine & Lapatinib | Superior OS1 (co-primary endpoint) Median OS: 29.9 vs 25.9 mo (HR 0.75, 95% CI 0.64-0.88) |
Krop et al. 2014 (TH3RESA) | 2011-09-14 to 2012-11-19 | Phase 3 (E-switch-ooc) | Physician's choice | Superior OS2 (co-primary endpoint) Median OS: 22.7 vs 15.8 mo (HR 0.68, 95% CI 0.54-0.85) |
Cortés et al. 2022 (DESTINY-Breast03) | 2018-2020 | Phase 3 (C) | Trastuzumab deruxtecan | Inferior OS |
1Reported efficacy for EMILIA is based on the 2017 update.
2Reported efficacy for TH3RESA is based on the 2017 update.
Antibody-drug conjugate therapy
- Trastuzumab emtansine (Kadcyla) 3.6 mg/kg IV once on day 1
21-day cycles
References
- EMILIA: Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh DY, Diéras V, Guardino E, Fang L, Lu MW, Olsen S, Blackwell K; EMILIA Study Group. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012 Nov 8;367(19):1783-91. Epub 2012 Oct 1. Erratum in: N Engl J Med. 2013 Jun 20;368(25):2442. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00829166
- PRO analysis: Welslau M, Diéras V, Sohn JH, Hurvitz SA, Lalla D, Fang L, Althaus B, Guardino E, Miles D. Patient-reported outcomes from EMILIA, a randomized phase 3 study of trastuzumab emtansine (T-DM1) versus capecitabine and lapatinib in human epidermal growth factor receptor 2-positive locally advanced or metastatic breast cancer. Cancer. 2014 Mar 1;120(5):642-51. Epub 2013 Nov 12. link to original article PubMed
- Update: Diéras V, Miles D, Verma S, Pegram M, Welslau M, Baselga J, Krop IE, Blackwell K, Hoersch S, Xu J, Green M, Gianni L. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2017 Jun;18(6):732-742. Epub 2017 May 16. link to original article link to PMC article PubMed
- TH3RESA: Krop IE, Kim SB, González-Martín A, LoRusso PM, Ferrero JM, Smitt M, Yu R, Leung AC, Wildiers H; TH3RESA study collaborators. Trastuzumab emtansine versus treatment of physician's choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014 Jun;15(7):689-99. Epub 2014 May 2. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT01419197
- Update: Krop IE, Kim SB, Martin AG, LoRusso PM, Ferrero JM, Badovinac-Crnjevic T, Hoersch S, Smitt M, Wildiers H. Trastuzumab emtansine versus treatment of physician's choice in patients with previously treated HER2-positive metastatic breast cancer (TH3RESA): final overall survival results from a randomised open-label phase 3 trial. Lancet Oncol. 2017 Jun;18(6):743-754. Epub 2017 May 16. link to original article PubMed
- DESTINY-Breast03: Cortés J, Kim SB, Chung WP, Im SA, Park YH, Hegg R, Kim MH, Tseng LM, Petry V, Chung CF, Iwata H, Hamilton E, Curigliano G, Xu B, Huang CS, Kim JH, Chiu JWY, Pedrini JL, Lee C, Liu Y, Cathcart J, Bako E, Verma S, Hurvitz SA; DESTINY-Breast03 Trial Investigators. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med. 2022 Mar 24;386(12):1143-1154. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT03529110
- Update: Hurvitz SA, Hegg R, Chung WP, Im SA, Jacot W, Ganju V, Chiu JWY, Xu B, Hamilton E, Madhusudan S, Iwata H, Altintas S, Henning JW, Curigliano G, Perez-Garcia JM, Kim SB, Petry V, Huang CS, Li W, Frenel JS, Antolin S, Yeo W, Bianchini G, Loi S, Tsurutani J, Egorov A, Liu Y, Cathcart J, Ashfaque S, Cortés J. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. Lancet. 2023 Jan 14;401(10371):105-117. Epub 2022 Dec 7. link to original article PubMed
- PRO analysis: Curigliano G, Dunton K, Rosenlund M, Janek M, Cathcart J, Liu Y, Fasching PA, Iwata H. Patient-reported outcomes and hospitalization data in patients with HER2-positive metastatic breast cancer receiving trastuzumab deruxtecan or trastuzumab emtansine in the phase III DESTINY-Breast03 study. Ann Oncol. 2023 Jul;34(7):569-577. Epub 2023 May 12. link to original article PubMed
- Subgroup analysis: Hurvitz SA, Kim SB, Chung WP, Im SA, Park YH, Hegg R, Kim MH, Tseng LM, Petry V, Chung CF, Iwata H, Hamilton E, Curigliano G, Xu B, Egorov A, Liu Y, Cathcart J, Bako E, Tecson K, Verma S, Cortés J. Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer patients with brain metastases from the randomized DESTINY-Breast03 trial. ESMO Open. 2024 May;9(5):102924. Epub 2024 Apr 24. link to original article link to PMC article PubMed
Vinorelbine & Margetuximab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rugo et al. 2021 (SOPHIA) | 2015-2018 | Phase 3 (E-RT-switch-ic) | 1a. Eribulin & Trastuzumab 1b. Gemcitabine & Trastuzumab 1c. VH 1d. XH |
Seems to have superior PFS (primary endpoint) Median PFS: 6 vs 5 mo (HR 0.76, 95% CI 0.59-0.98) Did not meet secondary endpoint of OS1 Median OS: 21.6 vs 21.9 mo (HR 0.95, 95% CI 0.77-1.17) |
1Reported efficacy is based on the 2022 update.
Chemotherapy
- Vinorelbine (Navelbine) 25 to 30 mg/m2 IV once per day on days 1 & 8
Targeted therapy
- Margetuximab (Margenza) 15 mg/kg IV over 120 minutes once on day 1
21-day cycles
References
- SOPHIA: Rugo HS, Im SA, Cardoso F, Cortés J, Curigliano G, Musolino A, Pegram MD, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Kaufman B, Yerushalmi R, Fasching PA, Nordstrom JL, Bonvini E, Koenig S, Edlich S, Hong S, Rock EP, Gradishar WJ; SOPHIA Study Group. Efficacy of Margetuximab vs Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Apr 1;7(4):573-584. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT02492711
- Update: Rugo HS, Im SA, Cardoso F, Cortes J, Curigliano G, Musolino A, Pegram MD, Bachelot T, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Schwartz GN, Pluard TJ, Ricci F, Gwin WR 3rd, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Gal-Yam EN, Yerushalmi R, Fasching PA, Kaufman PA, Ashley EJ, Perez-Olle R, Hong S, Rosales MK, Gradishar WJ; SOPHIA Study Group. Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial. J Clin Oncol. 2023 Jan 10;41(2):198-205. Epub 2022 Nov 4. link to original article link to PMC article PubMed
Vinorelbine & Trastuzumab (VH)
VH: Vinorelbine & Herceptin (Trastuzumab)
Regimen variant #1, 2 out of 3 weeks
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rugo et al. 2021 (SOPHIA) | 2015-2018 | Phase 3 (C) | 1a. Capecitabine & Margetuximab 1b. Eribulin & Margetuximab 1c. Gemcitabine & Margetuximab 1d. Vinorelbine & Margetuximab |
Seems to have inferior PFS |
Yamamoto et al. 2022 (PRECIOUS) | 2015-2018 | Phase 3 (C) | 1a. THP (Docetaxel) 1b. THP (Paclitaxel) 1c. nab-Paclitaxel, Pertuzumab, Trastuzumab 1d. VHP 1e. EHP 1f. XHP 1g. GHP |
Might have inferior OS |
Note: this is the lower bound of vinorelbine dosing specified in SOPHIA.
Prior treatment criteria
- PRECIOUS: History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this.
Chemotherapy
- Vinorelbine (Navelbine) 25 mg/m2 IV once per day on days 1 & 8
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
Regimen variant #2, 2 out of 3 weeks
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rugo et al. 2021 (SOPHIA) | 2015-2018 | Phase 3 (C) | 1a. Capecitabine & Margetuximab 1b. Eribulin & Margetuximab 1c. Gemcitabine & Margetuximab 1d. Vinorelbine & Margetuximab |
Seems to have inferior PFS |
Note: this is the upper bound of vinorelbine dosing specified in SOPHIA.
Chemotherapy
- Vinorelbine (Navelbine) 30 mg/m2 IV once per day on days 1 & 8
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
Regimen variant #3, weekly
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
André et al. 2014 (BOLERO-3) | 2009-2012 | Phase 3 (C) | VH & Everolimus | Inferior PFS |
Harbeck et al. 2016 (LUX-Breast 1) | 2010-2013 | Phase 3 (C) | Afatinib & Vinorelbine | Did not meet primary endpoint of PFS Median PFS: 5.6 vs 5.5 mo (HR 0.91, 95% CI 0.71-1.16) |
Chemotherapy
- Vinorelbine (Navelbine) 25 mg/m2 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1
- Cycle 2 onwards: 2 mg/kg IV once on day 1
7-day cycles
References
- BOLERO-3: André F, O'Regan R, Ozguroglu M, Toi M, Xu B, Jerusalem G, Masuda N, Wilks S, Arena F, Isaacs C, Yap YS, Papai Z, Lang I, Armstrong A, Lerzo G, White M, Shen K, Litton J, Chen D, Zhang Y, Ali S, Taran T, Gianni L. Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2014 May;15(6):580-91. Epub 2014 Apr 14. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01007942
- LUX-Breast 1: Harbeck N, Huang CS, Hurvitz S, Yeh DC, Shao Z, Im SA, Jung KH, Shen K, Ro J, Jassem J, Zhang Q, Im YH, Wojtukiewicz M, Sun Q, Chen SC, Goeldner RG, Uttenreuther-Fischer M, Xu B, Piccart-Gebhart M; LUX-Breast 1 study group. Afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one previous trastuzumab treatment (LUX-Breast 1): an open-label, randomised, phase 3 trial. Lancet Oncol. 2016 Mar;17(3):357-66. Epub 2016 Jan 26. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01125566
- SOPHIA: Rugo HS, Im SA, Cardoso F, Cortés J, Curigliano G, Musolino A, Pegram MD, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Kaufman B, Yerushalmi R, Fasching PA, Nordstrom JL, Bonvini E, Koenig S, Edlich S, Hong S, Rock EP, Gradishar WJ; SOPHIA Study Group. Efficacy of Margetuximab vs Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Apr 1;7(4):573-584. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT02492711
- Update: Rugo HS, Im SA, Cardoso F, Cortes J, Curigliano G, Musolino A, Pegram MD, Bachelot T, Wright GS, Saura C, Escrivá-de-Romaní S, De Laurentiis M, Schwartz GN, Pluard TJ, Ricci F, Gwin WR 3rd, Levy C, Brown-Glaberman U, Ferrero JM, de Boer M, Kim SB, Petráková K, Yardley DA, Freedman O, Jakobsen EH, Gal-Yam EN, Yerushalmi R, Fasching PA, Kaufman PA, Ashley EJ, Perez-Olle R, Hong S, Rosales MK, Gradishar WJ; SOPHIA Study Group. Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial. J Clin Oncol. 2023 Jan 10;41(2):198-205. Epub 2022 Nov 4. link to original article link to PMC article PubMed
- PRECIOUS: Yamamoto Y, Iwata H, Taira N, Masuda N, Takahashi M, Yoshinami T, Ueno T, Toyama T, Yamanaka T, Takano T, Kashiwaba M, Tsugawa K, Hasegawa Y, Tamura K, Tada H, Hara F, Fujisawa T, Niikura N, Saji S, Morita S, Toi M, Ohno S. Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS). Cancer Sci. 2022 Sep;113(9):3169-3179. Epub 2022 Jul 23. link to original article link to PMC article dosing details in supplement have been reviewed by our editors PubMed UMIN000018202
- SWOG-S0347: NCT00103233
Vinorelbine & Trastuzumab (VH) & Everolimus
VH & Everolimus: Vinorelbine, Herceptin (Trastuzumab), Everolimus
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
André et al. 2014 (BOLERO-3) | 2009-2012 | Phase 3 (E-esc) | VH | Superior PFS (primary endpoint) Median PFS: 7 vs 5.8 mo (HR 0.78, 95% CI 0.65-0.95) |
Chemotherapy
- Vinorelbine (Navelbine) 25 mg/m2 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1
- Cycle 2 onwards: 2 mg/kg IV once on day 1
- Everolimus (Afinitor) 5 mg PO once per day on days 1 to 7
7-day cycles
References
- BOLERO-3: André F, O'Regan R, Ozguroglu M, Toi M, Xu B, Jerusalem G, Masuda N, Wilks S, Arena F, Isaacs C, Yap YS, Papai Z, Lang I, Armstrong A, Lerzo G, White M, Shen K, Litton J, Chen D, Zhang Y, Ali S, Taran T, Gianni L. Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2014 May;15(6):580-91. Epub 2014 Apr 14. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01007942
VHP
VHP: Vinorelbine, Herceptin (Trastuzumab), Pertuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yamamoto et al. 2022 (PRECIOUS) | 2015-2018 | Phase 3 (E-esc) | 1a. TH (Docetaxel) 1b. TH (Paclitaxel) 1c. nab-Paclitaxel & Trastuzumab 1d. VH 1e. EH 1f. XH 1g. GH |
Might have superior OS1 (secondary endpoint) Median OS: 28.8 vs 23.4 mo (HR 0.71, 95% CI NA-1.03) Seems to have superior PFS (primary endpoint) Median PFS: 5.3 vs 4.2 mo (sHR 0.76, 95% CI NA-0.97) |
1Results are based on a one-sided statistical analysis.
Prior treatment criteria
- PRECIOUS: History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this.
Chemotherapy
- Vinorelbine (Navelbine) 25 mg/m2 IV once per day on days 1 & 8
Targeted therapy
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycle 2 onwards: 420 mg IV once on day 1
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
References
- PRECIOUS: Yamamoto Y, Iwata H, Taira N, Masuda N, Takahashi M, Yoshinami T, Ueno T, Toyama T, Yamanaka T, Takano T, Kashiwaba M, Tsugawa K, Hasegawa Y, Tamura K, Tada H, Hara F, Fujisawa T, Niikura N, Saji S, Morita S, Toi M, Ohno S. Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS). Cancer Sci. 2022 Sep;113(9):3169-3179. Epub 2022 Jul 23. link to original article link to PMC article dosing details in supplement have been reviewed by our editors PubMed UMIN000018202
XHP
XHP: Xeloda (Capecitabine), Herceptin (Trastuzumab), Pertuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Urruticoechea et al. 2017 (PHEREXA) | 2010-2013 | Phase 3 (E-esc) | Capecitabine & Trastuzumab | Might have superior PFS (primary endpoint) Median PFS: 11.1 vs 9 mo (HR 0.82, 95% CI 0.65-1.02) |
Yamamoto et al. 2022 (PRECIOUS) | 2015-2018 | Phase 3 (E-esc) | 1a. TH (Docetaxel) 1b. TH (Paclitaxel) 1c. nab-Paclitaxel & Trastuzumab 1d. VH 1e. EH 1f. XH 1g. GH |
Might have superior OS1 (secondary endpoint) Median OS: 28.8 vs 23.4 mo (HR 0.71, 95% CI NA-1.03) Seems to have superior PFS (primary endpoint) Median PFS: 5.3 vs 4.2 mo (sHR 0.76, 95% CI NA-0.97) |
1Results are based on a one-sided statistical analysis.
Prior treatment criteria
- PRECIOUS: History of pertuzumab and trastuzumab‐containing chemotherapy; pertuzumab not permitted in the regimen immediately prior to this.
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
Targeted therapy
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycle 2 onwards: 420 mg IV once on day 1
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
References
- PHEREXA: Urruticoechea A, Rizwanullah M, Im SA, Ruiz ACS, Láng I, Tomasello G, Douthwaite H, Badovinac Crnjevic T, Heeson S, Eng-Wong J, Muñoz M. Randomized phase III trial of trastuzumab plus capecitabine with or without pertuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who experienced disease progression during or after trastuzumab-based therapy. J Clin Oncol. 2017 Sep 10;35(26):3030-3038. Epub 2017 Apr 24. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01026142
- PRECIOUS: Yamamoto Y, Iwata H, Taira N, Masuda N, Takahashi M, Yoshinami T, Ueno T, Toyama T, Yamanaka T, Takano T, Kashiwaba M, Tsugawa K, Hasegawa Y, Tamura K, Tada H, Hara F, Fujisawa T, Niikura N, Saji S, Morita S, Toi M, Ohno S. Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS). Cancer Sci. 2022 Sep;113(9):3169-3179. Epub 2022 Jul 23. link to original article link to PMC article dosing details in supplement have been reviewed by our editors PubMed UMIN000018202
Maintenance for metastatic or unresectable disease
Pertuzumab & Trastuzumab
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Baselga et al. 2011 (CLEOPATRA) | 2008-2010 | Non-randomized part of phase 3 RCT |
Preceding treatment
- First-line THP (Docetaxel) for at least 6 cycles
Targeted therapy
- Pertuzumab (Perjeta) 420 mg IV once on day 1
- Trastuzumab (Herceptin) 6 mg/kg IV once on day 1
21-day cycles
References
- CLEOPATRA: Baselga J, Cortés J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, Clark E, Benyunes MC, Ross G, Swain SM; CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012 Jan 12;366(2):109-19. Epub 2011 Dec 7. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00567190
- Update: Swain SM, Kim SB, Cortés J, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Knott A, Clark E, Ross G, Benyunes MC, Baselga J. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2013 May;14(6):461-71. Epub 2013 Apr 18. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
- HRQoL analysis: Cortés J, Baselga J, Im YH, Im SA, Pivot X, Ross G, Clark E, Knott A, Swain SM. Health-related quality-of-life assessment in CLEOPATRA, a phase III study combining pertuzumab with trastuzumab and docetaxel in metastatic breast cancer. Ann Oncol. 2013 Oct;24(10):2630-2635. Epub 2013 Jul 17. link to original article PubMed
- Update: Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S, Clark E, Ross G, Benyunes MC, Cortés J; CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015 Feb 19;372(8):724-34. link to original article link to PMC article PubMed
- Update: Swain SM, Miles D, Kim SB, Im YH, Im SA, Semiglazov V, Ciruelos E, Schneeweiss A, Loi S, Monturus E, Clark E, Knott A, Restuccia E, Benyunes MC, Cortés J; CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020 Apr;21(4):519-530. Epub 2020 Mar 12. link to original article PubMed
Trastuzumab monotherapy
Regimen variant #1, q3wk dosing
Study | Dates of enrollment | Evidence |
---|---|---|
Perez et al. 2005 (NCCTG 983252) | 1999-04 to 2003-07 | Phase 2 |
Valero et al. 2010 (BCIRG 007) | 2001-2004 | Non-randomized part of phase 3 RCT |
Baselga et al. 2011 (CLEOPATRA) | 2008-2010 | Non-randomized part of phase 3 RCT |
Gelmon et al. 2015 (NCIC-CTG MA.31) | 2008-2011 | Non-randomized part of phase 3 RCT |
Preceding treatment
- NCCTG 983252: First-line TPC (q3wk) x 8
- BCIRG 007: First-line TH (Docetaxel) x 8 versus TCH (Taxotere) x 8
- CLEOPATRA: First-line TH (Docetaxel)
- NCIC-CTG MA.31: First-line TH (Paclitaxel) x 6 or TH (Docetaxel) x 8
Regimen variant #2, weekly dosing
Study | Dates of enrollment | Evidence |
---|---|---|
Robert et al. 2006 | 1998-2002 | Non-randomized part of phase 3 RCT |
Perez et al. 2005 (NCCTG 983252) | 1999-04 to 2003-07 | Phase 2 |
Marty et al. 2005 (M77001) | 2000-2002 | Non-randomized part of phase 2 RCT |
Preceding treatment
- M77001: First-line TH (Docetaxel) for at least 6 cycles
- NCCTG 983252: First-line TPC (weekly) x 6
- Robert et al. 2006: First-line TP x 6 versus TPC x 6
References
- M77001: Marty M, Cognetti F, Maraninchi D, Snyder R, Mauriac L, Tubiana-Hulin M, Chan S, Grimes D, Antón A, Lluch A, Kennedy J, O'Byrne K, Conte P, Green M, Ward C, Mayne K, Extra JM. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol. 2005 Jul 1;23(19):4265-74. Epub 2005 May 23. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- NCCTG 983252: Perez EA, Suman VJ, Rowland KM, Ingle JN, Salim M, Loprinzi CL, Flynn PJ, Mailliard JA, Kardinal CG, Krook JE, Thrower AR, Visscher DW, Jenkins RB. Two concurrent phase II trials of paclitaxel/carboplatin/trastuzumab (weekly or every-3-week schedule) as first-line therapy in women with HER2-overexpressing metastatic breast cancer: NCCTG study 983252. Clin Breast Cancer. 2005 Dec;6(5):425-32. link to original article dosing details in abstract have been reviewed by our editors PubMed
- Robert N, Leyland-Jones B, Asmar L, Belt R, Ilegbodu D, Loesch D, Raju R, Valentine E, Sayre R, Cobleigh M, Albain K, McCullough C, Fuchs L, Slamon D. Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer. J Clin Oncol. 2006 Jun 20;24(18):2786-92. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- BCIRG 007: Valero V, Forbes J, Pegram MD, Pienkowski T, Eiermann W, von Minckwitz G, Roche H, Martin M, Crown J, Mackey JR, Fumoleau P, Rolski J, Mrsic-Krmpotic Z, Jagiello-Gruszfeld A, Riva A, Buyse M, Taupin H, Sauter G, Press MF, Slamon DJ. Multicenter phase III randomized trial comparing docetaxel and trastuzumab with docetaxel, carboplatin, and trastuzumab as first-line chemotherapy for patients with HER2-gene-amplified metastatic breast cancer (BCIRG 007 study): two highly active therapeutic regimens. J Clin Oncol. 2011 Jan 10;29(2):149-56. Epub 2010 Nov 29. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00047255
- CLEOPATRA: Baselga J, Cortés J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, Clark E, Benyunes MC, Ross G, Swain SM; CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012 Jan 12;366(2):109-19. Epub 2011 Dec 7. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00567190
- Update: Swain SM, Kim SB, Cortés J, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Knott A, Clark E, Ross G, Benyunes MC, Baselga J. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2013 May;14(6):461-71. Epub 2013 Apr 18. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
- HRQoL analysis: Cortés J, Baselga J, Im YH, Im SA, Pivot X, Ross G, Clark E, Knott A, Swain SM. Health-related quality-of-life assessment in CLEOPATRA, a phase III study combining pertuzumab with trastuzumab and docetaxel in metastatic breast cancer. Ann Oncol. 2013 Oct;24(10):2630-2635. Epub 2013 Jul 17. link to original article PubMed
- Update: Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S, Clark E, Ross G, Benyunes MC, Cortés J; CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015 Feb 19;372(8):724-34. link to original article link to PMC article PubMed
- Update: Swain SM, Miles D, Kim SB, Im YH, Im SA, Semiglazov V, Ciruelos E, Schneeweiss A, Loi S, Monturus E, Clark E, Knott A, Restuccia E, Benyunes MC, Cortés J; CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020 Apr;21(4):519-530. Epub 2020 Mar 12. link to original article PubMed
- NCIC-CTG MA.31: Gelmon KA, Boyle FM, Kaufman B, Huntsman DG, Manikhas A, Di Leo A, Martin M, Schwartzberg LS, Lemieux J, Aparicio S, Shepherd LE, Dent S, Ellard SL, Tonkin K, Pritchard KI, Whelan TJ, Nomikos D, Nusch A, Coleman RE, Mukai H, Tjulandin S, Khasanov R, Rizel S, Connor AP, Santillana SL, Chapman JA, Parulekar WR. Lapatinib or trastuzumab plus taxane therapy for human epidermal growth factor receptor 2-positive advanced breast cancer: final results of NCIC-CTG MA.31. J Clin Oncol. 2015 May 10;33(14):1574-83. Epub 2015 Mar 16. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00667251