Difference between revisions of "Breast cancer, ER and HER2 co-expressing"
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− | {{#lst: | + | <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}} | ||
<big>'''Note: these are regimens tested in patients with hormone receptor-positive, HER2-positive breast cancer. Please see the [[breast cancer|main breast cancer page]], [[Breast cancer, ER-positive|ER+ breast cancer page]], and [[Breast cancer, HER2-positive|HER2+ breast cancer page]] for other regimens.'''</big> | <big>'''Note: these are regimens tested in patients with hormone receptor-positive, HER2-positive breast cancer. Please see the [[breast cancer|main breast cancer page]], [[Breast cancer, ER-positive|ER+ breast cancer page]], and [[Breast cancer, HER2-positive|HER2+ breast cancer page]] for other regimens.'''</big> | ||
{| class="wikitable" style="float:right; margin-right: 5px;" | {| class="wikitable" style="float:right; margin-right: 5px;" | ||
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|} | |} | ||
{{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.''' | ||
+ | ==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] | ||
+ | *'''2020:''' Allison et al. [https://doi.org/10.1200/jco.19.02309 Estrogen and Progesterone Receptor Testing in Breast Cancer: ASCO/CAP Guideline Update] [https://pubmed.ncbi.nlm.nih.gov/31928404/ PubMed] | ||
+ | **'''2010:''' Hammond et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2881855/ American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer] [https://pubmed.ncbi.nlm.nih.gov/20404251/ PubMed] | ||
+ | |||
+ | ==NCCN== | ||
+ | *''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].'' | ||
+ | |||
+ | =Neoadjuvant chemotherapy= | ||
+ | ==Trastuzumab emtansine monotherapy {{#subobject:ef98f0|Regimen=1}}== | ||
+ | T-DM1: '''<u>T</u>'''rastuzumab-'''<u>DM1</u>''' (Trastuzumab emtansine) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:91b517|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/10.1200/JCO.2016.71.9815 Harbeck et al. 2017 (WGSG ADAPT)] | ||
+ | |rowspan=2|2012-2015 | ||
+ | |rowspan=2 style="background-color:#1a9851"|Randomized Phase 2 (E-switch-ic) | ||
+ | |1. [[#T-DM1_.26_ET|T-DM1 & ET]] | ||
+ | |style="background-color:#d0d0d0"|Not reported | ||
+ | |- | ||
+ | |2. [[#Trastuzumab_.26_ET|Trastuzumab & ET]] | ||
+ | |style="background-color:#1a9850"|Superior pCR rate (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 cycle for 4 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] was performed within 3 weeks of the end of therapy. Adjuvant therapy consisted of [[Breast_cancer,_HER2-positive#EC-TH_.28Paclitaxel.29|EC-TH]], unless the patient had pCR in which case adjuvant therapy was optional | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''WGSG ADAPT:''' Harbeck N, Gluz O, Christgen M, Kates RE, Braun M, Küemmel S, Schumacher C, Potenberg J, Kraemer S, Kleine-Tebbe A, Augustin D, Aktas B, Forstbauer H, Tio J, von Schumann R, Liedtke C, Grischke EM, Schumacher J, Wuerstlein R, Kreipe HH, Nitz UA; West German Study Group. De-escalation strategies in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC): Final analysis of the West German Study Group Adjuvant Dynamic marker-Adjusted Personalized Therapy trial optimizing risk assessment and therapy response prediction in early BC HER2- and hormone receptor-positive phase II randomized trial-efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET. J Clin Oncol. 2017 Sep 10;35(26):3046-3054. Epub 2017 Jul 6. [https://doi.org/10.1200/JCO.2016.71.9815 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28682681/ PubMed] [https://clinicaltrials.gov/study/NCT01817452 NCT01817452] | ||
+ | ==T-DM1 & ET {{#subobject:207386|Regimen=1}}== | ||
+ | T-DM1 & ET: '''<u>T</u>'''rastuzumab-DM1 (Trastuzumab emtansine) & '''<u>E</u>'''ndocrine '''<u>T</u>'''herapy | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:b28ce1|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/10.1200/JCO.2016.71.9815 Harbeck et al. 2017 (WGSG ADAPT)] | ||
+ | |rowspan=2|2012-2015 | ||
+ | |rowspan=2 style="background-color:#1a9851"|Randomized Phase 2 (E-esc) | ||
+ | |1. [[#Trastuzumab_emtansine_monotherapy|T-DM1]] | ||
+ | |style="background-color:#d0d0d0"|Not reported | ||
+ | |- | ||
+ | |2. [[#Trastuzumab_.26_ET|Trastuzumab & ET]] | ||
+ | |style="background-color:#1a9850"|Superior pCR rate (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 | ||
+ | ====Endocrine therapy==== | ||
+ | *One of the following: | ||
+ | **Premenopausal women: [[Tamoxifen (Nolvadex)]] recommended | ||
+ | **[[:Category:GnRH_agonists|GnRH analogs]] were also allowed | ||
+ | **Postmenopausal women: [[:Category:Aromatase inhibitors|Aromatase inhibitor]] recommended | ||
+ | '''21-day cycle for 4 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] was performed within 3 weeks of the end of therapy. Adjuvant therapy consisted of [[Breast_cancer,_HER2-positive#EC-TH_.28Paclitaxel.29|EC-TH]], unless the patient had pCR in which case adjuvant therapy was optional | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''WGSG ADAPT:''' Harbeck N, Gluz O, Christgen M, Kates RE, Braun M, Küemmel S, Schumacher C, Potenberg J, Kraemer S, Kleine-Tebbe A, Augustin D, Aktas B, Forstbauer H, Tio J, von Schumann R, Liedtke C, Grischke EM, Schumacher J, Wuerstlein R, Kreipe HH, Nitz UA; West German Study Group. De-escalation strategies in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC): Final analysis of the West German Study Group Adjuvant Dynamic marker-Adjusted Personalized Therapy trial optimizing risk assessment and therapy response prediction in early BC HER2- and hormone receptor-positive phase II randomized trial-efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET. J Clin Oncol. 2017 Sep 10;35(26):3046-3054. Epub 2017 Jul 6. [https://doi.org/10.1200/JCO.2016.71.9815 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28682681/ PubMed] [https://clinicaltrials.gov/study/NCT01817452 NCT01817452] | ||
+ | ==Trastuzumab & ET {{#subobject:b9d62c|Regimen=1}}== | ||
+ | Trastuzumab & ET: Trastuzumab & '''<u>E</u>'''ndocrine '''<u>T</u>'''herapy | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:d0233|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.2016.71.9815 Harbeck et al. 2017 (WGSG ADAPT)] | ||
+ | |2012-2015 | ||
+ | |style="background-color:#1a9851"|Randomized Phase 2 (C) | ||
+ | |1. [[#Trastuzumab_emtansine_monotherapy|T-DM1]]<br>2. [[#T-DM1_.26_ET|T-DM1 & ET]] | ||
+ | |style="background-color:#d73027"|Inferior pCR rate | ||
+ | |- | ||
+ | |} | ||
+ | <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 4: 6 mg/kg IV once on day 1 | ||
+ | ====Endocrine therapy==== | ||
+ | *Endocrine therapy by the following criteria: | ||
+ | **Premenopausal women: [[Tamoxifen (Nolvadex)]] recommended | ||
+ | ***[[:Category:GnRH_agonists|GnRH analogs]] were also allowed | ||
+ | **Postmenopausal women: [[:Category:Aromatase inhibitors|Aromatase inhibitor]] recommended | ||
+ | '''21-day cycle for 4 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[Surgery#Breast_cancer_surgery|Surgery]] was performed within 3 weeks of the end of therapy. Adjuvant therapy consisted of [[Breast_cancer,_HER2-positive#EC-TH_.28Paclitaxel.29|EC-TH]], unless the patient had pCR in which case adjuvant therapy was optional | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''WGSG ADAPT:''' Harbeck N, Gluz O, Christgen M, Kates RE, Braun M, Küemmel S, Schumacher C, Potenberg J, Kraemer S, Kleine-Tebbe A, Augustin D, Aktas B, Forstbauer H, Tio J, von Schumann R, Liedtke C, Grischke EM, Schumacher J, Wuerstlein R, Kreipe HH, Nitz UA; West German Study Group. De-escalation strategies in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC): Final analysis of the West German Study Group Adjuvant Dynamic marker-Adjusted Personalized Therapy trial optimizing risk assessment and therapy response prediction in early BC HER2- and hormone receptor-positive phase II randomized trial-efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET. J Clin Oncol. 2017 Sep 10;35(26):3046-3054. Epub 2017 Jul 6. [https://doi.org/10.1200/JCO.2016.71.9815 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28682681/ PubMed] [https://clinicaltrials.gov/study/NCT01817452 NCT01817452] | ||
+ | =Adjuvant therapy= | ||
+ | ==Anastrozole monotherapy {{#subobject:79h35|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:gav33c|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.clinicaltrials.gov/study/NCT04752332 Awaiting publication (eMonarcHER)] | ||
+ | |2021-ongoing | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |[[#ET_.26_Abemaciclib_666|ET & Abemaciclib]] | ||
+ | | style="background-color:#d3d3d3" |In progress | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *Adjuvant [[Regimen_classes#Anti-HER2-based_regimen|HER2-targeted therapy]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Endocrine therapy==== | ||
+ | *[[Anastrozole (Arimidex)]] 1 mg PO once per day | ||
+ | '''Up to 10-year course''' | ||
+ | </div></div> | ||
+ | |||
+ | ===References=== | ||
+ | #'''eMonarcHER:''' [https://clinicaltrials.gov/study/NCT04752332 NCT04752332] | ||
=Metastatic disease, first-line therapy= | =Metastatic disease, first-line therapy= | ||
==Anastrozole monotherapy {{#subobject:796bb|Regimen=1}}== | ==Anastrozole monotherapy {{#subobject:796bb|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:bd033c|Variant=1}}=== | ===Regimen {{#subobject:bd033c|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 24: | Line 174: | ||
|[https://doi.org/10.1200/JCO.2008.20.6847 Kaufman et al. 2009 (TAnDEM)] | |[https://doi.org/10.1200/JCO.2008.20.6847 Kaufman et al. 2009 (TAnDEM)] | ||
|2001-2004 | |2001-2004 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
|[[#Anastrozole_.26_Trastuzumab|Anastrozole & Trastuzumab]] | |[[#Anastrozole_.26_Trastuzumab|Anastrozole & Trastuzumab]] | ||
| style="background-color:#d73027" |Inferior PFS | | style="background-color:#d73027" |Inferior PFS | ||
|- | |- | ||
|} | |} | ||
− | ==== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[Anastrozole (Arimidex)]] 1 mg PO once per day | + | ====Endocrine therapy==== |
− | + | *[[Anastrozole (Arimidex)]] 1 mg PO once per day on days 1 to 28 | |
'''28-day cycles''' | '''28-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''TAnDEM:''' Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, Tjulandin S, Jahn M, Lehle M, Feyereislova A, Révil C, Jones A. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol. 2009 Nov 20;27(33):5529-37. Epub 2009 Sep 28. [https://doi.org/10.1200/JCO.2008.20.6847 link to original article] '''contains | + | # '''TAnDEM:''' Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, Tjulandin S, Jahn M, Lehle M, Feyereislova A, Révil C, Jones A. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol. 2009 Nov 20;27(33):5529-37. Epub 2009 Sep 28. [https://doi.org/10.1200/JCO.2008.20.6847 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19786670/ PubMed] [https://clinicaltrials.gov/study/NCT00022672 NCT00022672] |
− | |||
==Anastrozole & Trastuzumab {{#subobject:8077ad|Regimen=1}}== | ==Anastrozole & Trastuzumab {{#subobject:8077ad|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen variant #1, weekly trastuzumab {{#subobject:e6f8f0|Variant=1}}=== | ===Regimen variant #1, weekly trastuzumab {{#subobject:e6f8f0|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 51: | Line 198: | ||
|[https://doi.org/10.1200/JCO.2008.20.6847 Kaufman et al. 2009 (TAnDEM)] | |[https://doi.org/10.1200/JCO.2008.20.6847 Kaufman et al. 2009 (TAnDEM)] | ||
|2001-2004 | |2001-2004 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
− | |[[# | + | |[[#Anastrozole_monotherapy_2|Anastrozole]] |
− | | style="background-color:#1a9850" |Superior PFS | + | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 4.8 vs 2.4 mo<br>(HR 0.63, 95% CI 0.47-0.84) |
|- | |- | ||
|} | |} | ||
− | ==== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[Anastrozole (Arimidex)]] 1 mg PO once per day | + | ====Endocrine therapy==== |
+ | *[[Anastrozole (Arimidex)]] 1 mg PO once per day on days 1 to 28 | ||
====Targeted therapy==== | ====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, 22 | **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 | **Cycle 2 onwards: 2 mg/kg IV once per day on days 1, 8, 15, 22 | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, q3wk trastuzumab {{#subobject:ugibx4|Variant=1}}=== | ===Regimen variant #2, q3wk trastuzumab {{#subobject:ugibx4|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 75: | Line 223: | ||
|rowspan=2|[https://doi.org/10.1200/jco.20.01894 Johnston et al. 2020 (ALTERNATIVE)] | |rowspan=2|[https://doi.org/10.1200/jco.20.01894 Johnston et al. 2020 (ALTERNATIVE)] | ||
|rowspan=2|2011-2016 | |rowspan=2|2011-2016 | ||
− | |rowspan=2 style="background-color:#1a9851"|Phase | + | |rowspan=2 style="background-color:#1a9851"|Phase 3 (C) |
− | | | + | |1a. [[#Anastrozole_.26_Lapatinib_999|Anastrozole & Lapatinib]]<br>1b. [[#Exemestane_.26_Lapatinib_999|Exemestane & Lapatinib]]<br> 1c. [[#Lapatinib_.26_Letrozole|Lapatinib & Letrozole]] |
− | | style="background-color:# | + | | style="background-color:#ffffbf" |Did not meet secondary endpoint of PFS |
|- | |- | ||
− | | | + | |2a. [[#Anastrozole.2C_Lapatinib.2C_Trastuzumab|Anastrozole, Lapatinib, Trastuzumab]]<br>2b. [[#Exemestane.2C_Lapatinib.2C_Trastuzumab|Exemestane, Lapatinib, Trastuzumab]]<br>2c. [[#Lapatinib.2C_Letrozole.2C_Trastuzumab|Lapatinib, Letrozole, Trastuzumab]] |
| style="background-color:#d73027" |Inferior PFS | | style="background-color:#d73027" |Inferior PFS | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377763/ Hua et al. 2022 (SYSUCC-002)] | ||
+ | |2013-2019 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-switch-ooc) | ||
+ | |1a. [[#Paclitaxel_.26_Trastuzumab_.28TH.29|TH (Paclitaxel)]]<br>1b. [[#Docetaxel_.26_Trastuzumab_.28TH.29|TH (Docetaxel)]]<br>1c. [[#Vinorelbine_.26_Trastuzumab_.28VH.29|VH]]<br>1d. [[#Capecitabine_.26_Trastuzumab_.28XH.29|XH]] | ||
+ | | style="background-color:#eeee01" |Non-inferior PFS (primary endpoint)<br>Median PFS: 19.2 vs 14.8 mo<br>(HR 0.88, 95% CI 0.71-1.09) | ||
|- | |- | ||
|} | |} | ||
− | ''Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.'' | + | ''Note: the original ALTERNATIVE article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published. Hua et al. 2022 does not contain dosing instructions for anastrozole.'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====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 | ||
**Cycle 2 onwards: 6 mg/kg IV once on day 1 | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
− | ==== | + | ====Endocrine therapy==== |
− | *[[Anastrozole (Arimidex)]] 1 mg PO once per day | + | *[[Anastrozole (Arimidex)]] 1 mg PO once per day on days 1 to 21 |
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''TAnDEM:''' Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, Tjulandin S, Jahn M, Lehle M, Feyereislova A, Révil C, Jones A. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol. 2009 Nov 20;27(33):5529-37. Epub 2009 Sep 28. [https://doi.org/10.1200/JCO.2008.20.6847 link to original article] '''contains | + | # '''TAnDEM:''' Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, Tjulandin S, Jahn M, Lehle M, Feyereislova A, Révil C, Jones A. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol. 2009 Nov 20;27(33):5529-37. Epub 2009 Sep 28. [https://doi.org/10.1200/JCO.2008.20.6847 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19786670/ PubMed] [https://clinicaltrials.gov/study/NCT00022672 NCT00022672] |
− | <!--- # '''RETRACTED:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: ALTERNATIVE. J Clin Oncol. 2018 Mar 10;36(8):741-748. Epub 2017 Dec 15. [https://doi.org/10.1200/JCO.2017.74.7824 link to original article] '''contains | + | <!--- # '''RETRACTED:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: ALTERNATIVE. J Clin Oncol. 2018 Mar 10;36(8):741-748. Epub 2017 Dec 15. [https://doi.org/10.1200/JCO.2017.74.7824 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29244528/ PubMed] --> |
− | # '''ALTERNATIVE:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. [https://doi.org/10.1200/jco.20.01894 link to original article] '''contains | + | # '''ALTERNATIVE:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. [https://doi.org/10.1200/jco.20.01894 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32822287/ PubMed] [https://clinicaltrials.gov/study/NCT01160211 NCT01160211] |
− | + | # '''SYSUCC-002:''' Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. [https://doi.org/10.1158/1078-0432.ccr-21-3435 link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377763/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34810217/ PubMed] [https://clinicaltrials.gov/study/NCT01950182 NCT01950182] | |
==Anastrozole, Lapatinib, Trastuzumab {{#subobject:gg0dbc|Regimen=1}}== | ==Anastrozole, Lapatinib, Trastuzumab {{#subobject:gg0dbc|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:ug8a84|Variant=1}}=== | ===Regimen {{#subobject:ug8a84|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 113: | Line 264: | ||
|rowspan=2|[https://doi.org/10.1200/jco.20.01894 Johnston et al. 2020 (ALTERNATIVE)] | |rowspan=2|[https://doi.org/10.1200/jco.20.01894 Johnston et al. 2020 (ALTERNATIVE)] | ||
|rowspan=2|2011-2016 | |rowspan=2|2011-2016 | ||
− | |rowspan=2 style="background-color:#1a9851"|Phase | + | |rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc) |
− | | | + | |1a. [[#Anastrozole_.26_Lapatinib_999|Anastrozole & Lapatinib]]<br>1b. [[#Exemestane_.26_Lapatinib_999|Exemestane & Lapatinib]]<br>1c. [[#Lapatinib_.26_Letrozole|Lapatinib & Letrozole]] |
| style="background-color:#d3d3d3" |Not reported | | style="background-color:#d3d3d3" |Not reported | ||
|- | |- | ||
− | | | + | |2a. [[#Anastrozole_.26_Trastuzumab|Anastrozole & Trastuzumab]]<br>2b. [[#Exemestane_.26.Trastuzumab|Exemestane & Trastuzumab]]<br>2c. [[#Letrozole_.26_Trastuzumab|Letrozole & Trastuzumab]] |
− | | style="background-color:#1a9850" |Superior PFS | + | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 11 vs 5.6 mo<br>(HR 0.62, 95% CI 0.45-0.88) |
|- | |- | ||
|} | |} | ||
''Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.'' | ''Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | *[[Lapatinib (Tykerb)]] 1000 mg PO once per day | + | *[[Lapatinib (Tykerb)]] 1000 mg PO once per day on days 1 to 21 |
*[[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 | ||
**Cycle 2 onwards: 6 mg/kg IV once on day 1 | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
− | ==== | + | ====Endocrine therapy==== |
− | *[[Anastrozole (Arimidex)]] 1 mg PO once per day | + | *[[Anastrozole (Arimidex)]] 1 mg PO once per day on days 1 to 21 |
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | <!--- # '''RETRACTED:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: ALTERNATIVE. J Clin Oncol. 2018 Mar 10;36(8):741-748. Epub 2017 Dec 15. [https://doi.org/10.1200/JCO.2017.74.7824 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29244528/ PubMed] --> | ||
+ | # '''ALTERNATIVE:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. [https://doi.org/10.1200/jco.20.01894 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32822287/ PubMed] [https://clinicaltrials.gov/study/NCT01160211 NCT01160211] | ||
+ | ==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:a1b284|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/PMC9377763/ Hua et al. 2022 (SYSUCC-002)] | ||
+ | |2013-2019 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#Anastrozole_.26_Trastuzumab|Anastrozole & Trastuzumab]]<br>1b. [[#Exemestane_.26_Trastuzumab|Exemestane & Trastuzumab]]<br>1c. [[#Letrozole_.26_Trastuzumab|Letrozole & Trastuzumab]]<br>1d. [[#Tamoxifen_.26_Trastuzumab|Tamoxifen & Trastuzumab]]<br>1e. [[#Toremifene_.26_Trastuzumab|Toremifene & Trastuzumab]] | ||
+ | | style="background-color:#eeee01" |Non-inferior PFS (primary endpoint) | ||
+ | |- | ||
+ | |} | ||
+ | <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> | ||
+ | ===References=== | ||
+ | # '''SYSUCC-002:''' Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. [https://doi.org/10.1158/1078-0432.ccr-21-3435 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377763/ link to PMC article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/34810217/ PubMed] [https://clinicaltrials.gov/study/NCT01950182 NCT01950182] | ||
+ | ==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 {{#subobject:a1bzcn|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/PMC9377763/ Hua et al. 2022 (SYSUCC-002)] | ||
+ | |2013-2019 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#Anastrozole_.26_Trastuzumab|Anastrozole & Trastuzumab]]<br>1b. [[#Exemestane_.26_Trastuzumab|Exemestane & Trastuzumab]]<br>1c. [[#Letrozole_.26_Trastuzumab|Letrozole & Trastuzumab]]<br>1d. [[#Tamoxifen_.26_Trastuzumab|Tamoxifen & Trastuzumab]]<br>1e. [[#Toremifene_.26_Trastuzumab|Toremifene & Trastuzumab]] | ||
+ | | style="background-color:#eeee01" |Non-inferior PFS (primary endpoint) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Docetaxel (Taxotere)]] 75 to 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 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | # '''SYSUCC-002:''' Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. [https://doi.org/10.1158/1078-0432.ccr-21-3435 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377763/ link to PMC article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/34810217/ PubMed] [https://clinicaltrials.gov/study/NCT01950182 NCT01950182] | |
− | |||
==Exemestane & Trastuzumab {{#subobject:ugjxbc|Regimen=1}}== | ==Exemestane & Trastuzumab {{#subobject:ugjxbc|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:1yga84|Variant=1}}=== | ===Regimen {{#subobject:1yga84|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 151: | Line 358: | ||
|rowspan=2|[https://doi.org/10.1200/jco.20.01894 Johnston et al. 2020 (ALTERNATIVE)] | |rowspan=2|[https://doi.org/10.1200/jco.20.01894 Johnston et al. 2020 (ALTERNATIVE)] | ||
|rowspan=2|2011-2016 | |rowspan=2|2011-2016 | ||
− | |rowspan=2 style="background-color:#1a9851"|Phase | + | |rowspan=2 style="background-color:#1a9851"|Phase 3 (C) |
− | | | + | |1a. [[#Anastrozole_.26_Lapatinib_999|Anastrozole & Lapatinib]]<br>1b. [[#Exemestane_.26_Lapatinib_999|Exemestane & Lapatinib]]<br>1c. [[#Lapatinib_.26_Letrozole|Lapatinib & Letrozole]] |
− | | style="background-color:# | + | | style="background-color:#ffffbf" |Did not meet secondary endpoint of PFS |
|- | |- | ||
− | | | + | |2a. [[#Anastrozole.2C_Lapatinib.2C_Trastuzumab|Anastrozole, Lapatinib, Trastuzumab]]<br>2b. [[#Exemestane.2C_Lapatinib.2C_Trastuzumab|Exemestane, Lapatinib, Trastuzumab]]<br>2c. [[#Lapatinib.2C_Letrozole.2C_Trastuzumab|Lapatinib, Letrozole, Trastuzumab]] |
| style="background-color:#d73027" |Inferior PFS | | style="background-color:#d73027" |Inferior PFS | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377763/ Hua et al. 2022 (SYSUCC-002)] | ||
+ | |2013-2019 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-switch-ooc) | ||
+ | |1a. [[#Paclitaxel_.26_Trastuzumab_.28TH.29|TH (Paclitaxel)]]<br>1b. [[#Docetaxel_.26_Trastuzumab_.28TH.29|TH (Docetaxel)]]<br>1c. [[#Vinorelbine_.26_Trastuzumab_.28VH.29|VH]]<br>1d. [[#Capecitabine_.26_Trastuzumab_.28XH.29|XH]] | ||
+ | | style="background-color:#eeee01" |Non-inferior PFS (primary endpoint)<br>Median PFS: 19.2 vs 14.8 mo<br>(HR 0.88, 95% CI 0.71-1.09) | ||
|- | |- | ||
|} | |} | ||
− | ''Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.'' | + | ''Note: the original ALTERNATIVE article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published. Hua et al. 2022 does not contain dosing instructions for exemestane.'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====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 | ||
**Cycle 2 onwards: 6 mg/kg IV once on day 1 | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
− | ==== | + | ====Endocrine therapy==== |
− | *[[Exemestane (Aromasin)]] 1 mg PO once per day | + | *[[Exemestane (Aromasin)]] 1 mg PO once per day on days 1 to 21 |
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | <!--- # '''RETRACTED:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: ALTERNATIVE. J Clin Oncol. 2018 Mar 10;36(8):741-748. Epub 2017 Dec 15. [https://doi.org/10.1200/JCO.2017.74.7824 link to original article] '''contains | + | <!--- # '''RETRACTED:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: ALTERNATIVE. J Clin Oncol. 2018 Mar 10;36(8):741-748. Epub 2017 Dec 15. [https://doi.org/10.1200/JCO.2017.74.7824 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29244528/ PubMed] --> |
− | # '''ALTERNATIVE:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. [https://doi.org/10.1200/jco.20.01894 link to original article] '''contains | + | # '''ALTERNATIVE:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. [https://doi.org/10.1200/jco.20.01894 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32822287/ PubMed] [https://clinicaltrials.gov/study/NCT01160211 NCT01160211] |
+ | # '''SYSUCC-002:''' Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. [https://doi.org/10.1158/1078-0432.ccr-21-3435 link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377763/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34810217/ PubMed] [https://clinicaltrials.gov/study/NCT01950182 NCT01950182] | ||
==Exemestane, Lapatinib, Trastuzumab {{#subobject:hh0dbc|Regimen=1}}== | ==Exemestane, Lapatinib, Trastuzumab {{#subobject:hh0dbc|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:258gja|Variant=1}}=== | ===Regimen {{#subobject:258gja|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 187: | Line 399: | ||
|rowspan=2|[https://doi.org/10.1200/jco.20.01894 Johnston et al. 2020 (ALTERNATIVE)] | |rowspan=2|[https://doi.org/10.1200/jco.20.01894 Johnston et al. 2020 (ALTERNATIVE)] | ||
|rowspan=2|2011-2016 | |rowspan=2|2011-2016 | ||
− | |rowspan=2 style="background-color:#1a9851"|Phase | + | |rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc) |
− | | | + | |1a. [[#Anastrozole_.26_Lapatinib_999|Anastrozole & Lapatinib]]<br>1b. [[#Exemestane_.26_Lapatinib_999|Exemestane & Lapatinib]]<br>1c. [[#Lapatinib_.26_Letrozole|Lapatinib & Letrozole]] |
| style="background-color:#d3d3d3" |Not reported | | style="background-color:#d3d3d3" |Not reported | ||
|- | |- | ||
− | | | + | |2a. [[#Anastrozole_.26_Trastuzumab|Anastrozole & Trastuzumab]]<br>2b. [[#Exemestane_.26.Trastuzumab|Exemestane & Trastuzumab]]<br>2c. [[#Letrozole_.26_Trastuzumab|Letrozole & Trastuzumab]] |
− | | style="background-color:#1a9850" |Superior PFS | + | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 11 vs 5.6 mo<br>(HR 0.62, 95% CI 0.45-0.88) |
|- | |- | ||
|} | |} | ||
''Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.'' | ''Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | *[[Lapatinib (Tykerb)]] 1000 mg PO once per day | + | *[[Lapatinib (Tykerb)]] 1000 mg PO once per day on days 1 to 21 |
*[[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 | ||
**Cycle 2 onwards: 6 mg/kg IV once on day 1 | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
− | ==== | + | ====Endocrine therapy==== |
− | *[[Exemestane (Aromasin)]] 25 mg PO once per day | + | *[[Exemestane (Aromasin)]] 25 mg PO once per day on days 1 to 21 |
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | <!--- # '''RETRACTED:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: ALTERNATIVE. J Clin Oncol. 2018 Mar 10;36(8):741-748. Epub 2017 Dec 15. [https://doi.org/10.1200/JCO.2017.74.7824 link to original article] '''contains | + | <!--- # '''RETRACTED:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: ALTERNATIVE. J Clin Oncol. 2018 Mar 10;36(8):741-748. Epub 2017 Dec 15. [https://doi.org/10.1200/JCO.2017.74.7824 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29244528/ PubMed] --> |
− | # '''ALTERNATIVE:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. [https://doi.org/10.1200/jco.20.01894 link to original article] '''contains | + | # '''ALTERNATIVE:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. [https://doi.org/10.1200/jco.20.01894 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32822287/ PubMed] [https://clinicaltrials.gov/study/NCT01160211 NCT01160211] |
− | |||
==Lapatinib & Letrozole {{#subobject:5fba83|Regimen=1}}== | ==Lapatinib & Letrozole {{#subobject:5fba83|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:879969|Variant=1}}=== | ===Regimen {{#subobject:879969|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 225: | Line 433: | ||
|[https://doi.org/10.1200/JCO.2009.23.3734 Johnston et al. 2009 (EGF30008)] | |[https://doi.org/10.1200/JCO.2009.23.3734 Johnston et al. 2009 (EGF30008)] | ||
|2003-2006 | |2003-2006 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-RT-esc) |
|[[#Letrozole_monotherapy_3|Letrozole]] | |[[#Letrozole_monotherapy_3|Letrozole]] | ||
− | | style="background-color:#91cf60" |Seems to have superior PFS | + | | style="background-color:#91cf60" |Seems to have superior PFS (primary endpoint)<br>Median PFS: 8.2 vs 3 mo<br>(HR 0.71, 95% CI 0.53-0.96) |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Lapatinib (Tykerb)]] 1500 mg PO once per day | *[[Lapatinib (Tykerb)]] 1500 mg PO once per day | ||
− | ==== | + | ====Endocrine therapy==== |
*[[Letrozole (Femara)]] 2.5 mg PO once per day | *[[Letrozole (Femara)]] 2.5 mg PO once per day | ||
− | |||
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''EGF30008:''' Johnston S, Pippen J Jr, Pivot X, Lichinitser M, Sadeghi S, Dieras V, Gomez HL, Romieu G, Manikhas A, Kennedy MJ, Press MF, Maltzman J, Florance A, O'Rourke L, Oliva C, Stein S, Pegram M. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 2009 Nov 20;27(33):5538-46. Epub 2009 Sep 28. [https://doi.org/10.1200/JCO.2009.23.3734 link to original article] '''contains | + | # '''EGF30008:''' Johnston S, Pippen J Jr, Pivot X, Lichinitser M, Sadeghi S, Dieras V, Gomez HL, Romieu G, Manikhas A, Kennedy MJ, Press MF, Maltzman J, Florance A, O'Rourke L, Oliva C, Stein S, Pegram M. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 2009 Nov 20;27(33):5538-46. Epub 2009 Sep 28. [https://doi.org/10.1200/JCO.2009.23.3734 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19786658/ PubMed] [https://clinicaltrials.gov/study/NCT00073528 NCT00073528] |
− | |||
==Lapatinib, Letrozole, Trastuzumab {{#subobject:ee0dbc|Regimen=1}}== | ==Lapatinib, Letrozole, Trastuzumab {{#subobject:ee0dbc|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:251384|Variant=1}}=== | ===Regimen {{#subobject:251384|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 255: | Line 459: | ||
|rowspan=2|[https://doi.org/10.1200/jco.20.01894 Johnston et al. 2020 (ALTERNATIVE)] | |rowspan=2|[https://doi.org/10.1200/jco.20.01894 Johnston et al. 2020 (ALTERNATIVE)] | ||
|rowspan=2|2011-2016 | |rowspan=2|2011-2016 | ||
− | |rowspan=2 style="background-color:#1a9851"|Phase | + | |rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc) |
− | | | + | |1a. [[#Anastrozole_.26_Lapatinib_999|Anastrozole & Lapatinib]]<br>1b. [[#Exemestane_.26_Lapatinib_999|Exemestane & Lapatinib]]<br>1c. [[#Lapatinib_.26_Letrozole|Lapatinib & Letrozole]] |
| style="background-color:#d3d3d3" |Not reported | | style="background-color:#d3d3d3" |Not reported | ||
|- | |- | ||
− | | | + | |2a. [[#Anastrozole_.26_Trastuzumab|Anastrozole & Trastuzumab]]<br>2b. [[#Exemestane_.26.Trastuzumab|Exemestane & Trastuzumab]]<br>2c. [[#Letrozole_.26_Trastuzumab|Letrozole & Trastuzumab]] |
− | | style="background-color:#1a9850" |Superior PFS | + | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 11 vs 5.6 mo<br>(HR 0.62, 95% CI 0.45-0.88) |
|- | |- | ||
|} | |} | ||
''Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.'' | ''Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | *[[Lapatinib (Tykerb)]] 1000 mg PO once per day | + | *[[Lapatinib (Tykerb)]] 1000 mg PO once per day on days 1 to 21 |
*[[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 | ||
**Cycle 2 onwards: 6 mg/kg IV once on day 1 | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
− | ==== | + | ====Endocrine therapy==== |
− | *[[Letrozole (Femara)]] 2.5 mg PO once per day | + | *[[Letrozole (Femara)]] 2.5 mg PO once per day on days 1 to 21 |
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | <!--- # '''RETRACTED:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: ALTERNATIVE. J Clin Oncol. 2018 Mar 10;36(8):741-748. Epub 2017 Dec 15. [https://doi.org/10.1200/JCO.2017.74.7824 link to original article] '''contains | + | <!--- # '''RETRACTED:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: ALTERNATIVE. J Clin Oncol. 2018 Mar 10;36(8):741-748. Epub 2017 Dec 15. [https://doi.org/10.1200/JCO.2017.74.7824 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29244528/ PubMed] --> |
− | # '''ALTERNATIVE:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. [https://doi.org/10.1200/jco.20.01894 link to original article] '''contains | + | # '''ALTERNATIVE:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. [https://doi.org/10.1200/jco.20.01894 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32822287/ PubMed] [https://clinicaltrials.gov/study/NCT01160211 NCT01160211] |
− | |||
==Letrozole monotherapy {{#subobject:75d541|Regimen=1}}== | ==Letrozole monotherapy {{#subobject:75d541|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:d7ef99|Variant=1}}=== | ===Regimen {{#subobject:d7ef99|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 293: | Line 493: | ||
|[https://doi.org/10.1200/JCO.2009.23.3734 Johnston et al. 2009 (EGF30008)] | |[https://doi.org/10.1200/JCO.2009.23.3734 Johnston et al. 2009 (EGF30008)] | ||
|2003-2006 | |2003-2006 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (C) |
|[[#Lapatinib_.26_Letrozole|Lapatinib & Letrozole]] | |[[#Lapatinib_.26_Letrozole|Lapatinib & Letrozole]] | ||
| style="background-color:#fc8d59" |Seems to have inferior PFS | | style="background-color:#fc8d59" |Seems to have inferior PFS | ||
|- | |- | ||
|} | |} | ||
− | ==== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[Letrozole (Femara)]] 2.5 mg PO once per day | + | ====Endocrine therapy==== |
− | + | *[[Letrozole (Femara)]] 2.5 mg PO once per day on days 1 to 28 | |
'''28-day cycles''' | '''28-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''EGF30008:''' Johnston S, Pippen J Jr, Pivot X, Lichinitser M, Sadeghi S, Dieras V, Gomez HL, Romieu G, Manikhas A, Kennedy MJ, Press MF, Maltzman J, Florance A, O'Rourke L, Oliva C, Stein S, Pegram M. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 2009 Nov 20;27(33):5538-46. Epub 2009 Sep 28. [https://doi.org/10.1200/JCO.2009.23.3734 link to original article] '''contains | + | # '''EGF30008:''' Johnston S, Pippen J Jr, Pivot X, Lichinitser M, Sadeghi S, Dieras V, Gomez HL, Romieu G, Manikhas A, Kennedy MJ, Press MF, Maltzman J, Florance A, O'Rourke L, Oliva C, Stein S, Pegram M. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 2009 Nov 20;27(33):5538-46. Epub 2009 Sep 28. [https://doi.org/10.1200/JCO.2009.23.3734 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19786658/ PubMed] [https://clinicaltrials.gov/study/NCT00073528 NCT00073528] |
− | |||
==Letrozole & Trastuzumab {{#subobject:8ugz41|Regimen=1}}== | ==Letrozole & Trastuzumab {{#subobject:8ugz41|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:6cq284|Variant=1}}=== | ===Regimen {{#subobject:6cq284|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 320: | Line 517: | ||
|rowspan=2|[https://doi.org/10.1200/jco.20.01894 Johnston et al. 2020 (ALTERNATIVE)] | |rowspan=2|[https://doi.org/10.1200/jco.20.01894 Johnston et al. 2020 (ALTERNATIVE)] | ||
|rowspan=2|2011-2016 | |rowspan=2|2011-2016 | ||
− | |rowspan=2 style="background-color:#1a9851"|Phase | + | |rowspan=2 style="background-color:#1a9851"|Phase 3 (C) |
− | | | + | |1a. [[#Anastrozole_.26_Lapatinib_999|Anastrozole & Lapatinib]]<br>1b. [[#Exemestane_.26_Lapatinib_999|Exemestane & Lapatinib]]<br>1c. [[#Lapatinib_.26_Letrozole|Lapatinib & Letrozole]] |
− | | style="background-color:# | + | | style="background-color:#ffffbf" |Did not meet secondary endpoint of PFS |
|- | |- | ||
− | | | + | |2a. [[#Anastrozole.2C_Lapatinib.2C_Trastuzumab|Anastrozole, Lapatinib, Trastuzumab]]<br>2b. [[#Exemestane.2C_Lapatinib.2C_Trastuzumab|Exemestane, Lapatinib, Trastuzumab]]<br>2c. [[#Lapatinib.2C_Letrozole.2C_Trastuzumab|Lapatinib, Letrozole, Trastuzumab]] |
| style="background-color:#d73027" |Inferior PFS | | style="background-color:#d73027" |Inferior PFS | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377763/ Hua et al. 2022 (SYSUCC-002)] | ||
+ | |2013-2019 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-switch-ooc) | ||
+ | |1a. [[#Paclitaxel_.26_Trastuzumab_.28TH.29|TH (Paclitaxel)]]<br>1b. [[#Docetaxel_.26_Trastuzumab_.28TH.29|TH (Docetaxel)]]<br>1c. [[#Vinorelbine_.26_Trastuzumab_.28VH.29|VH]]<br>1d. [[#Capecitabine_.26_Trastuzumab_.28XH.29|XH]] | ||
+ | | style="background-color:#eeee01" |Non-inferior PFS (primary endpoint)<br>Median PFS: 19.2 vs 14.8 mo<br>(HR 0.88, 95% CI 0.71-1.09) | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: the original ALTERNATIVE article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published. Hua et al. does not contain dosing instructions for letrozole.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====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 | ||
+ | ====Endocrine therapy==== | ||
+ | *[[Letrozole (Femara)]] 2.5 mg PO once per day on days 1 to 21 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | <!--- # '''RETRACTED:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: ALTERNATIVE. J Clin Oncol. 2018 Mar 10;36(8):741-748. Epub 2017 Dec 15. [https://doi.org/10.1200/JCO.2017.74.7824 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29244528/ PubMed] --> | ||
+ | # '''ALTERNATIVE:''' Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. [https://doi.org/10.1200/jco.20.01894 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32822287/ PubMed] [https://clinicaltrials.gov/study/NCT01160211 NCT01160211] | ||
+ | # '''SYSUCC-002:''' Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. [https://doi.org/10.1158/1078-0432.ccr-21-3435 link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377763/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34810217/ PubMed] [https://clinicaltrials.gov/study/NCT01950182 NCT01950182] | ||
+ | ==Paclitaxel & Trastuzumab (TH) {{#subobject:aa22dd|Regimen=1}}== | ||
+ | TH: '''<u>T</u>'''axol (Paclitaxel), '''<u>H</u>'''erceptin (Trastuzumab) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:a1ga84|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/PMC9377763/ Hua et al. 2022 (SYSUCC-002)] | ||
+ | |2013-2019 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#Anastrozole_.26_Trastuzumab|Anastrozole & Trastuzumab]]<br>1b. [[#Exemestane_.26_Trastuzumab|Exemestane & Trastuzumab]]<br>1c. [[#Letrozole_.26_Trastuzumab|Letrozole & Trastuzumab]]<br>1d. [[#Tamoxifen_.26_Trastuzumab|Tamoxifen & Trastuzumab]]<br>1e. [[#Toremifene_.26_Trastuzumab|Toremifene & Trastuzumab]] | ||
+ | | style="background-color:#eeee01" |Non-inferior 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 | ||
+ | ====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=== | ||
+ | # '''SYSUCC-002:''' Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. [https://doi.org/10.1158/1078-0432.ccr-21-3435 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377763/ link to PMC article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/34810217/ PubMed] [https://clinicaltrials.gov/study/NCT01950182 NCT01950182] | ||
+ | ==Tamoxifen & Trastuzumab {{#subobject:8jnc41|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:1tex84|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/PMC9377763/ Hua et al. 2022 (SYSUCC-002)] | ||
+ | |2013-2019 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-switch-ooc) | ||
+ | |1a. [[#Paclitaxel_.26_Trastuzumab_.28TH.29|TH (Paclitaxel)]]<br>1b. [[#Docetaxel_.26_Trastuzumab_.28TH.29|TH (Docetaxel)]]<br>1c. [[#Vinorelbine_.26_Trastuzumab_.28VH.29|VH]]<br>1d. [[#Capecitabine_.26_Trastuzumab_.28XH.29|XH]] | ||
+ | | style="background-color:#eeee01" |Non-inferior PFS (primary endpoint)<br>Median PFS: 19.2 vs 14.8 mo<br>(HR 0.88, 95% CI 0.71-1.09) | ||
|- | |- | ||
|} | |} | ||
− | ''Note: | + | ''Note: Hua et al. 2022 does not contain dosing instructions for tamoxifen; this is a commonly used dosage.'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====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 | ||
+ | ====Endocrine therapy==== | ||
+ | *[[Tamoxifen (Nolvadex)]] 20 mg PO once per day on days 1 to 21 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''SYSUCC-002:''' Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. [https://doi.org/10.1158/1078-0432.ccr-21-3435 link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377763/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34810217/ PubMed] [https://clinicaltrials.gov/study/NCT01950182 NCT01950182] | ||
+ | ==Toremifene & Trastuzumab {{#subobject:torc41|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:1tecx5|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/PMC9377763/ Hua et al. 2022 (SYSUCC-002)] | ||
+ | |2013-2019 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-switch-ooc) | ||
+ | |1a. [[#Paclitaxel_.26_Trastuzumab_.28TH.29|TH (Paclitaxel)]]<br>1b. [[#Docetaxel_.26_Trastuzumab_.28TH.29|TH (Docetaxel)]]<br>1c. [[#Vinorelbine_.26_Trastuzumab_.28VH.29|VH]]<br>1d. [[#Capecitabine_.26_Trastuzumab_.28XH.29|XH]] | ||
+ | | style="background-color:#eeee01" |Non-inferior PFS (primary endpoint)<br>Median PFS: 19.2 vs 14.8 mo<br>(HR 0.88, 95% CI 0.71-1.09) | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: Hua et al. 2022 does not contain dosing instructions for toremifene; this is a commonly used dosage.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====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 | ||
**Cycle 2 onwards: 6 mg/kg IV once on day 1 | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
− | ==== | + | ====Endocrine therapy==== |
− | *[[ | + | *[[Toremifene (Fareston)]] 60 mg PO once per day on days 1 to 21 |
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''SYSUCC-002:''' Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. [https://doi.org/10.1158/1078-0432.ccr-21-3435 link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377763/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34810217/ PubMed] [https://clinicaltrials.gov/study/NCT01950182 NCT01950182] | ||
+ | ==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, IV {{#subobject:hgu44n|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/PMC9377763/ Hua et al. 2022 (SYSUCC-002)] | ||
+ | |2013-2019 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#Anastrozole_.26_Trastuzumab|Anastrozole & Trastuzumab]]<br>1b. [[#Exemestane_.26_Trastuzumab|Exemestane & Trastuzumab]]<br>1c. [[#Letrozole_.26_Trastuzumab|Letrozole & Trastuzumab]]<br>1d. [[#Tamoxifen_.26_Trastuzumab|Tamoxifen & Trastuzumab]]<br>1e. [[#Toremifene_.26_Trastuzumab|Toremifene & Trastuzumab]] | ||
+ | | style="background-color:#eeee01" |Non-inferior PFS (primary endpoint) | ||
+ | |- | ||
+ | |} | ||
+ | <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, PO {{#subobject:hur42n|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/PMC9377763/ Hua et al. 2022 (SYSUCC-002)] | ||
+ | |2013-2019 | ||
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
+ | |1a. [[#Anastrozole_.26_Trastuzumab|Anastrozole & Trastuzumab]]<br>1b. [[#Exemestane_.26_Trastuzumab|Exemestane & Trastuzumab]]<br>1c. [[#Letrozole_.26_Trastuzumab|Letrozole & Trastuzumab]]<br>1d. [[#Tamoxifen_.26_Trastuzumab|Tamoxifen & Trastuzumab]]<br>1e. [[#Toremifene_.26_Trastuzumab|Toremifene & Trastuzumab]] | ||
+ | | style="background-color:#eeee01" |Non-inferior PFS (primary endpoint) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Vinorelbine (Navelbine)]] 60 to 80 mg/m<sup>2</sup> PO 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''' | '''21-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | # '''SYSUCC-002:''' Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. [https://doi.org/10.1158/1078-0432.ccr-21-3435 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377763/ link to PMC article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/34810217/ PubMed] [https://clinicaltrials.gov/study/NCT01950182 NCT01950182] | |
− | |||
[[Category:Breast cancer regimens]] | [[Category:Breast cancer regimens]] | ||
[[Category:Biomarker-specific pages]] | [[Category:Biomarker-specific pages]] | ||
[[Category:Malignant breast neoplasm]] | [[Category:Malignant breast neoplasm]] |
Latest revision as of 12:11, 23 June 2024
Section editor | |
---|---|
TBA |
Note: these are regimens tested in patients with hormone receptor-positive, HER2-positive breast cancer. Please see the main breast cancer page, ER+ breast cancer page, and HER2+ breast cancer page for other regimens.
19 regimens on this page
21 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/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
- 2020: Allison et al. Estrogen and Progesterone Receptor Testing in Breast Cancer: ASCO/CAP Guideline Update PubMed
NCCN
- NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Breast Cancer.
Neoadjuvant chemotherapy
Trastuzumab emtansine monotherapy
T-DM1: Trastuzumab-DM1 (Trastuzumab emtansine)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Harbeck et al. 2017 (WGSG ADAPT) | 2012-2015 | Randomized Phase 2 (E-switch-ic) | 1. T-DM1 & ET | Not reported |
2. Trastuzumab & ET | Superior pCR rate (primary endpoint) |
Antibody-drug conjugate therapy
- Trastuzumab emtansine (Kadcyla) 3.6 mg/kg IV once on day 1
21-day cycle for 4 cycles
References
- WGSG ADAPT: Harbeck N, Gluz O, Christgen M, Kates RE, Braun M, Küemmel S, Schumacher C, Potenberg J, Kraemer S, Kleine-Tebbe A, Augustin D, Aktas B, Forstbauer H, Tio J, von Schumann R, Liedtke C, Grischke EM, Schumacher J, Wuerstlein R, Kreipe HH, Nitz UA; West German Study Group. De-escalation strategies in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC): Final analysis of the West German Study Group Adjuvant Dynamic marker-Adjusted Personalized Therapy trial optimizing risk assessment and therapy response prediction in early BC HER2- and hormone receptor-positive phase II randomized trial-efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET. J Clin Oncol. 2017 Sep 10;35(26):3046-3054. Epub 2017 Jul 6. link to original article contains dosing details in manuscript PubMed NCT01817452
T-DM1 & ET
T-DM1 & ET: Trastuzumab-DM1 (Trastuzumab emtansine) & Endocrine Therapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Harbeck et al. 2017 (WGSG ADAPT) | 2012-2015 | Randomized Phase 2 (E-esc) | 1. T-DM1 | Not reported |
2. Trastuzumab & ET | Superior pCR rate (primary endpoint) |
Antibody-drug conjugate therapy
- Trastuzumab emtansine (Kadcyla) 3.6 mg/kg IV once on day 1
Endocrine therapy
- One of the following:
- Premenopausal women: Tamoxifen (Nolvadex) recommended
- GnRH analogs were also allowed
- Postmenopausal women: Aromatase inhibitor recommended
21-day cycle for 4 cycles
References
- WGSG ADAPT: Harbeck N, Gluz O, Christgen M, Kates RE, Braun M, Küemmel S, Schumacher C, Potenberg J, Kraemer S, Kleine-Tebbe A, Augustin D, Aktas B, Forstbauer H, Tio J, von Schumann R, Liedtke C, Grischke EM, Schumacher J, Wuerstlein R, Kreipe HH, Nitz UA; West German Study Group. De-escalation strategies in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC): Final analysis of the West German Study Group Adjuvant Dynamic marker-Adjusted Personalized Therapy trial optimizing risk assessment and therapy response prediction in early BC HER2- and hormone receptor-positive phase II randomized trial-efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET. J Clin Oncol. 2017 Sep 10;35(26):3046-3054. Epub 2017 Jul 6. link to original article contains dosing details in manuscript PubMed NCT01817452
Trastuzumab & ET
Trastuzumab & ET: Trastuzumab & Endocrine Therapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Harbeck et al. 2017 (WGSG ADAPT) | 2012-2015 | Randomized Phase 2 (C) | 1. T-DM1 2. T-DM1 & ET |
Inferior pCR rate |
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
Endocrine therapy
- Endocrine therapy by the following criteria:
- Premenopausal women: Tamoxifen (Nolvadex) recommended
- GnRH analogs were also allowed
- Postmenopausal women: Aromatase inhibitor recommended
- Premenopausal women: Tamoxifen (Nolvadex) recommended
21-day cycle for 4 cycles
References
- WGSG ADAPT: Harbeck N, Gluz O, Christgen M, Kates RE, Braun M, Küemmel S, Schumacher C, Potenberg J, Kraemer S, Kleine-Tebbe A, Augustin D, Aktas B, Forstbauer H, Tio J, von Schumann R, Liedtke C, Grischke EM, Schumacher J, Wuerstlein R, Kreipe HH, Nitz UA; West German Study Group. De-escalation strategies in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC): Final analysis of the West German Study Group Adjuvant Dynamic marker-Adjusted Personalized Therapy trial optimizing risk assessment and therapy response prediction in early BC HER2- and hormone receptor-positive phase II randomized trial-efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET. J Clin Oncol. 2017 Sep 10;35(26):3046-3054. Epub 2017 Jul 6. link to original article contains dosing details in manuscript PubMed NCT01817452
Adjuvant therapy
Anastrozole monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Awaiting publication (eMonarcHER) | 2021-ongoing | Phase 3 (C) | ET & Abemaciclib | In progress |
Preceding treatment
- Adjuvant HER2-targeted therapy
References
- eMonarcHER: NCT04752332
Metastatic disease, first-line therapy
Anastrozole monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kaufman et al. 2009 (TAnDEM) | 2001-2004 | Phase 3 (C) | Anastrozole & Trastuzumab | Inferior PFS |
References
- TAnDEM: Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, Tjulandin S, Jahn M, Lehle M, Feyereislova A, Révil C, Jones A. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol. 2009 Nov 20;27(33):5529-37. Epub 2009 Sep 28. link to original article contains dosing details in abstract PubMed NCT00022672
Anastrozole & Trastuzumab
Regimen variant #1, weekly trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kaufman et al. 2009 (TAnDEM) | 2001-2004 | Phase 3 (E-esc) | Anastrozole | Superior PFS (primary endpoint) Median PFS: 4.8 vs 2.4 mo (HR 0.63, 95% CI 0.47-0.84) |
Endocrine therapy
- Anastrozole (Arimidex) 1 mg PO once per day on days 1 to 28
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 #2, q3wk trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Johnston et al. 2020 (ALTERNATIVE) | 2011-2016 | Phase 3 (C) | 1a. Anastrozole & Lapatinib 1b. Exemestane & Lapatinib 1c. Lapatinib & Letrozole |
Did not meet secondary endpoint of PFS |
2a. Anastrozole, Lapatinib, Trastuzumab 2b. Exemestane, Lapatinib, Trastuzumab 2c. Lapatinib, Letrozole, Trastuzumab |
Inferior PFS | |||
Hua et al. 2022 (SYSUCC-002) | 2013-2019 | Phase 3 (E-switch-ooc) | 1a. TH (Paclitaxel) 1b. TH (Docetaxel) 1c. VH 1d. XH |
Non-inferior PFS (primary endpoint) Median PFS: 19.2 vs 14.8 mo (HR 0.88, 95% CI 0.71-1.09) |
Note: the original ALTERNATIVE article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published. Hua et al. 2022 does not contain dosing instructions for anastrozole.
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
Endocrine therapy
- Anastrozole (Arimidex) 1 mg PO once per day on days 1 to 21
21-day cycles
References
- TAnDEM: Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, Tjulandin S, Jahn M, Lehle M, Feyereislova A, Révil C, Jones A. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol. 2009 Nov 20;27(33):5529-37. Epub 2009 Sep 28. link to original article contains dosing details in abstract PubMed NCT00022672
- ALTERNATIVE: Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. link to original article contains dosing details in manuscript PubMed NCT01160211
- SYSUCC-002: Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. link to original article contains partial protocol link to PMC article PubMed NCT01950182
Anastrozole, Lapatinib, Trastuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Johnston et al. 2020 (ALTERNATIVE) | 2011-2016 | Phase 3 (E-esc) | 1a. Anastrozole & Lapatinib 1b. Exemestane & Lapatinib 1c. Lapatinib & Letrozole |
Not reported |
2a. Anastrozole & Trastuzumab 2b. Exemestane & Trastuzumab 2c. Letrozole & Trastuzumab |
Superior PFS (primary endpoint) Median PFS: 11 vs 5.6 mo (HR 0.62, 95% CI 0.45-0.88) |
Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.
Targeted therapy
- Lapatinib (Tykerb) 1000 mg PO once 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
Endocrine therapy
- Anastrozole (Arimidex) 1 mg PO once per day on days 1 to 21
21-day cycles
References
- ALTERNATIVE: Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. link to original article contains dosing details in manuscript PubMed NCT01160211
Capecitabine & Trastuzumab (XH)
XH: Xeloda (Capecitabine) & Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hua et al. 2022 (SYSUCC-002) | 2013-2019 | Phase 3 (C) | 1a. Anastrozole & Trastuzumab 1b. Exemestane & Trastuzumab 1c. Letrozole & Trastuzumab 1d. Tamoxifen & Trastuzumab 1e. Toremifene & Trastuzumab |
Non-inferior PFS (primary endpoint) |
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
References
- SYSUCC-002: Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. link to original article link to PMC article contains dosing details in supplement PubMed NCT01950182
Docetaxel & Trastuzumab (TH)
TH: Taxotere (Docetaxel) & Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hua et al. 2022 (SYSUCC-002) | 2013-2019 | Phase 3 (C) | 1a. Anastrozole & Trastuzumab 1b. Exemestane & Trastuzumab 1c. Letrozole & Trastuzumab 1d. Tamoxifen & Trastuzumab 1e. Toremifene & Trastuzumab |
Non-inferior PFS (primary endpoint) |
Chemotherapy
- Docetaxel (Taxotere) 75 to 100 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
- SYSUCC-002: Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. link to original article link to PMC article contains dosing details in supplement PubMed NCT01950182
Exemestane & Trastuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Johnston et al. 2020 (ALTERNATIVE) | 2011-2016 | Phase 3 (C) | 1a. Anastrozole & Lapatinib 1b. Exemestane & Lapatinib 1c. Lapatinib & Letrozole |
Did not meet secondary endpoint of PFS |
2a. Anastrozole, Lapatinib, Trastuzumab 2b. Exemestane, Lapatinib, Trastuzumab 2c. Lapatinib, Letrozole, Trastuzumab |
Inferior PFS | |||
Hua et al. 2022 (SYSUCC-002) | 2013-2019 | Phase 3 (E-switch-ooc) | 1a. TH (Paclitaxel) 1b. TH (Docetaxel) 1c. VH 1d. XH |
Non-inferior PFS (primary endpoint) Median PFS: 19.2 vs 14.8 mo (HR 0.88, 95% CI 0.71-1.09) |
Note: the original ALTERNATIVE article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published. Hua et al. 2022 does not contain dosing instructions for exemestane.
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
Endocrine therapy
- Exemestane (Aromasin) 1 mg PO once per day on days 1 to 21
21-day cycles
References
- ALTERNATIVE: Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. link to original article contains dosing details in manuscript PubMed NCT01160211
- SYSUCC-002: Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. link to original article contains partial protocol link to PMC article PubMed NCT01950182
Exemestane, Lapatinib, Trastuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Johnston et al. 2020 (ALTERNATIVE) | 2011-2016 | Phase 3 (E-esc) | 1a. Anastrozole & Lapatinib 1b. Exemestane & Lapatinib 1c. Lapatinib & Letrozole |
Not reported |
2a. Anastrozole & Trastuzumab 2b. Exemestane & Trastuzumab 2c. Letrozole & Trastuzumab |
Superior PFS (primary endpoint) Median PFS: 11 vs 5.6 mo (HR 0.62, 95% CI 0.45-0.88) |
Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.
Targeted therapy
- Lapatinib (Tykerb) 1000 mg PO once 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
Endocrine therapy
- Exemestane (Aromasin) 25 mg PO once per day on days 1 to 21
21-day cycles
References
- ALTERNATIVE: Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. link to original article contains dosing details in manuscript PubMed NCT01160211
Lapatinib & Letrozole
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Johnston et al. 2009 (EGF30008) | 2003-2006 | Phase 3 (E-RT-esc) | Letrozole | Seems to have superior PFS (primary endpoint) Median PFS: 8.2 vs 3 mo (HR 0.71, 95% CI 0.53-0.96) |
Targeted therapy
- Lapatinib (Tykerb) 1500 mg PO once per day
Endocrine therapy
- Letrozole (Femara) 2.5 mg PO once per day
Continued indefinitely
References
- EGF30008: Johnston S, Pippen J Jr, Pivot X, Lichinitser M, Sadeghi S, Dieras V, Gomez HL, Romieu G, Manikhas A, Kennedy MJ, Press MF, Maltzman J, Florance A, O'Rourke L, Oliva C, Stein S, Pegram M. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 2009 Nov 20;27(33):5538-46. Epub 2009 Sep 28. link to original article contains dosing details in abstract PubMed NCT00073528
Lapatinib, Letrozole, Trastuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Johnston et al. 2020 (ALTERNATIVE) | 2011-2016 | Phase 3 (E-esc) | 1a. Anastrozole & Lapatinib 1b. Exemestane & Lapatinib 1c. Lapatinib & Letrozole |
Not reported |
2a. Anastrozole & Trastuzumab 2b. Exemestane & Trastuzumab 2c. Letrozole & Trastuzumab |
Superior PFS (primary endpoint) Median PFS: 11 vs 5.6 mo (HR 0.62, 95% CI 0.45-0.88) |
Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.
Targeted therapy
- Lapatinib (Tykerb) 1000 mg PO once 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
Endocrine therapy
- Letrozole (Femara) 2.5 mg PO once per day on days 1 to 21
21-day cycles
References
- ALTERNATIVE: Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. link to original article contains dosing details in manuscript PubMed NCT01160211
Letrozole monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Johnston et al. 2009 (EGF30008) | 2003-2006 | Phase 3 (C) | Lapatinib & Letrozole | Seems to have inferior PFS |
References
- EGF30008: Johnston S, Pippen J Jr, Pivot X, Lichinitser M, Sadeghi S, Dieras V, Gomez HL, Romieu G, Manikhas A, Kennedy MJ, Press MF, Maltzman J, Florance A, O'Rourke L, Oliva C, Stein S, Pegram M. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 2009 Nov 20;27(33):5538-46. Epub 2009 Sep 28. link to original article contains dosing details in abstract PubMed NCT00073528
Letrozole & Trastuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Johnston et al. 2020 (ALTERNATIVE) | 2011-2016 | Phase 3 (C) | 1a. Anastrozole & Lapatinib 1b. Exemestane & Lapatinib 1c. Lapatinib & Letrozole |
Did not meet secondary endpoint of PFS |
2a. Anastrozole, Lapatinib, Trastuzumab 2b. Exemestane, Lapatinib, Trastuzumab 2c. Lapatinib, Letrozole, Trastuzumab |
Inferior PFS | |||
Hua et al. 2022 (SYSUCC-002) | 2013-2019 | Phase 3 (E-switch-ooc) | 1a. TH (Paclitaxel) 1b. TH (Docetaxel) 1c. VH 1d. XH |
Non-inferior PFS (primary endpoint) Median PFS: 19.2 vs 14.8 mo (HR 0.88, 95% CI 0.71-1.09) |
Note: the original ALTERNATIVE article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published. Hua et al. does not contain dosing instructions for letrozole.
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
Endocrine therapy
- Letrozole (Femara) 2.5 mg PO once per day on days 1 to 21
21-day cycles
References
- ALTERNATIVE: Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. link to original article contains dosing details in manuscript PubMed NCT01160211
- SYSUCC-002: Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. link to original article contains partial protocol link to PMC article PubMed NCT01950182
Paclitaxel & Trastuzumab (TH)
TH: Taxol (Paclitaxel), Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hua et al. 2022 (SYSUCC-002) | 2013-2019 | Phase 3 (C) | 1a. Anastrozole & Trastuzumab 1b. Exemestane & Trastuzumab 1c. Letrozole & Trastuzumab 1d. Tamoxifen & Trastuzumab 1e. Toremifene & Trastuzumab |
Non-inferior PFS (primary endpoint) |
Chemotherapy
- Paclitaxel (Taxol) 80 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
- SYSUCC-002: Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. link to original article link to PMC article contains dosing details in supplement PubMed NCT01950182
Tamoxifen & Trastuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hua et al. 2022 (SYSUCC-002) | 2013-2019 | Phase 3 (E-switch-ooc) | 1a. TH (Paclitaxel) 1b. TH (Docetaxel) 1c. VH 1d. XH |
Non-inferior PFS (primary endpoint) Median PFS: 19.2 vs 14.8 mo (HR 0.88, 95% CI 0.71-1.09) |
Note: Hua et al. 2022 does not contain dosing instructions for tamoxifen; this is a commonly used dosage.
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
Endocrine therapy
- Tamoxifen (Nolvadex) 20 mg PO once per day on days 1 to 21
21-day cycles
References
- SYSUCC-002: Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. link to original article contains partial protocol link to PMC article PubMed NCT01950182
Toremifene & Trastuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hua et al. 2022 (SYSUCC-002) | 2013-2019 | Phase 3 (E-switch-ooc) | 1a. TH (Paclitaxel) 1b. TH (Docetaxel) 1c. VH 1d. XH |
Non-inferior PFS (primary endpoint) Median PFS: 19.2 vs 14.8 mo (HR 0.88, 95% CI 0.71-1.09) |
Note: Hua et al. 2022 does not contain dosing instructions for toremifene; this is a commonly used dosage.
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
Endocrine therapy
- Toremifene (Fareston) 60 mg PO once per day on days 1 to 21
21-day cycles
References
- SYSUCC-002: Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. link to original article contains partial protocol link to PMC article PubMed NCT01950182
Vinorelbine & Trastuzumab (VH)
VH: Vinorelbine & Herceptin (Trastuzumab)
Regimen variant #1, IV
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hua et al. 2022 (SYSUCC-002) | 2013-2019 | Phase 3 (C) | 1a. Anastrozole & Trastuzumab 1b. Exemestane & Trastuzumab 1c. Letrozole & Trastuzumab 1d. Tamoxifen & Trastuzumab 1e. Toremifene & Trastuzumab |
Non-inferior PFS (primary endpoint) |
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, PO
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hua et al. 2022 (SYSUCC-002) | 2013-2019 | Phase 3 (C) | 1a. Anastrozole & Trastuzumab 1b. Exemestane & Trastuzumab 1c. Letrozole & Trastuzumab 1d. Tamoxifen & Trastuzumab 1e. Toremifene & Trastuzumab |
Non-inferior PFS (primary endpoint) |
Chemotherapy
- Vinorelbine (Navelbine) 60 to 80 mg/m2 PO 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
- SYSUCC-002: Hua X, Bi XW, Zhao JL, Shi YX, Lin Y, Wu ZY, Zhang YQ, Zhang LH, Zhang AQ, Huang H, Liu XM, Xu F, Guo Y, Xia W, Hong RX, Jiang KK, Xue C, An X, Zhong YY, Wang SS, Huang JJ, Yuan ZY. Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002). Clin Cancer Res. 2022 Feb 15;28(4):637-645. link to original article link to PMC article contains dosing details in supplement PubMed NCT01950182