Breast cancer, HER2-positive
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Are you looking for a regimen, but can't find it here? It is possible that we've moved it to the historical regimens page. For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!
Note: these are regimens tested in biomarker-specific populations, please see the main breast cancer page for other regimens.
- Regimens for ER/HER2 co-expressing ("double positive") breast cancer are here.
- Regimens for CNS metastases are here.
123 regimens on this page
201 variants on this page
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Guidelines
ASCO
- 2022: Ramakrishna et al. Management of Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases PubMed
- 2022: Giordano et al. Systemic Therapy for Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer PubMed
- 2021: Korde et al. Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer: ASCO Guideline PubMed
- 2020: Denduluri et al. Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer: ASCO Guideline Update PubMed
Older
- 2018: Ramakrishna et al. Recommendations on disease management for patients with advanced human epidermal growth factor receptor 2-positive breast cancer and brain metastases: American Society of Clinical Oncology clinical practice guideline update PubMed
- 2018: Giordano et al. Systemic therapy for patients with advanced human epidermal growth factor receptor 2–positive breast cancer: ASCO Clinical Practice Guideline update PubMed
- 2018: Denduluri et al. Selection of optimal adjuvant chemotherapy and targeted therapy for early breast cancer: ASCO clinical practice guideline focused update PubMed
- 2016: Harris et al. Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: American Society of Clinical Oncology Clinical Practice Guideline PubMed
- 2015: Van Poznak et al. Use of biomarkers to guide decisions on systemic therapy for women with metastatic breast cancer: American Society of Clinical Oncology Clinical Practice Guideline PubMed
- 2014: Giordano et al. Systemic therapy for patients with advanced human epidermal growth factor receptor 2-positive breast cancer: American Society of Clinical Oncology clinical practice guideline PubMed
- 2014: Ramakrishna et al. Recommendations on disease management for patients with advanced human epidermal growth factor receptor 2-positive breast cancer and brain metastases: American Society of Clinical Oncology clinical practice guideline PubMed
ESMO
- 2023: Tarantino et al. ESMO expert consensus statements (ECS) on the definition, diagnosis, and management of HER2-low breast cancer PubMed
- 2017: Cardoso et al. 3rd ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3). PubMed
- 2015: Senkus et al. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. PubMed
NCCN
- NCCN does not have guidelines at this granular level; please see NCCN Guidelines - Breast Cancer.
St Gallen Breast Guidelines
- 2019: Burstein et al. Estimating the benefits of therapy for early-stage breast cancer: the St. Gallen International Consensus Guidelines for the primary therapy of early breast cancer 2019 PubMed
Older
- 2017: Curigliano et al. St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2017 PubMed
- 2015: Coates et al. Tailoring therapies—improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015 PubMed
Neoadjuvant therapy, sequential regimens
AC-TH (Paclitaxel)
AC-TH: Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxol (Paclitaxel) & Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Robidoux et al. 2013 (NSABP B-41) | 2007-2011 | Phase 3 (C) | 1. AC-THL | Might have inferior pCR rate |
2. AC-TL | Did not meet primary endpoint of pCR rate |
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22
- Cycles 6 to 8: 2 mg/kg IV once per day on days 1, 8, 15, 22
21-day cycle for 4 cycles, then 28-day cycle for 4 cycles
Subsequent treatment
- Surgery, then adjuvant trastuzumab for a total of 52 weeks of therapy.
References
- NSABP B-41: Robidoux A, Tang G, Rastogi P, Geyer CE Jr, Azar CA, Atkins JN, Fehrenbacher L, Bear HD, Baez-Diaz L, Sarwar S, Margolese RG, Farrar WB, Brufsky AM, Shibata HR, Bandos H, Paik S, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1183-92. Epub 2013 Oct 4. link to original article contains dosing details in abstract PubMed NCT00486668
AC-THL (Paclitaxel)
AC-THL: Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxol (Paclitaxel), Herceptin (Trastuzumab), Lapatinib
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Robidoux et al. 2013 (NSABP B-41) | 2007-2011 | Phase 3 (E-esc) | 1. AC-TH | Might have superior pCR rate (primary endpoint) |
2. AC-TL | Might have superior pCR rate (primary endpoint) |
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Chemotherapy, THL portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, THL portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22
- Cycles 6 to 8: 2 mg/kg IV once per day on days 1, 8, 15, 22
- Lapatinib (Tykerb) as follows:
- Cycles 5 to 8: 750 mg PO once per day
21-day cycle for 4 cycles, then 28-day cycle for 4 cycles
Subsequent treatment
- Surgery, then adjuvant trastuzumab for a total of 52 weeks of therapy
References
- NSABP B-41: Robidoux A, Tang G, Rastogi P, Geyer CE Jr, Azar CA, Atkins JN, Fehrenbacher L, Bear HD, Baez-Diaz L, Sarwar S, Margolese RG, Farrar WB, Brufsky AM, Shibata HR, Bandos H, Paik S, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1183-92. Epub 2013 Oct 4. link to original article contains dosing details in abstract PubMed NCT00486668
AC-THP (Docetaxel)
AC-THP: Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxotere (Docetaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tan et al. 2021 (FeDeriCa) | 2018-06-14 to 2018-12-24 | Phase 3 (C) | 1a. ddAC-THP (Paclitaxel, Phesgo) 1b. AC-THP (Docetaxel, Phesgo) |
Non-inferior serum trough |
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, THP portion (cycles 5 to 8)
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 8: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 8: 420 mg IV once on day 1
21-day cycle for 8 cycles
References
- FeDeriCa: Tan AR, Im SA, Mattar A, Colomer R, Stroyakovskii D, Nowecki Z, De Laurentiis M, Pierga JY, Jung KH, Schem C, Hogea A, Badovinac Crnjevic T, Heeson S, Shivhare M, Kirschbrown WP, Restuccia E, Jackisch C; FeDeriCa study group. Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection plus chemotherapy in HER2-positive early breast cancer (FeDeriCa): a randomised, open-label, multicentre, non-inferiority, phase 3 study. Lancet Oncol. 2021 Jan;22(1):85-97. Epub 2020 Dec 21. Erratum in: Lancet Oncol. 2021 Feb;22(2):e42. link to original article PubMed NCT03493854
AC-THP (Docetaxel, Phesgo)
AC-THP (Phesgo): Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxotere (Docetaxel) and Phesgo
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tan et al. 2021 (FeDeriCa) | 2018-06-14 to 2018-12-24 | Phase 3 (E-RT-switch-ic) | 1a. ddAC-THP 1b. AC-THP |
Non-inferior serum trough |
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Chemotherapy, THP (Phesgo) portion
- Docetaxel (Taxotere) as follows:
- Cycle 5: 75 mg/m2 IV once on day 1
- Cycles 6 to 8, if tolerated: 100 mg/m2 IV once on day 1
Targeted therapy, THP (Phesgo) portion
- Pertuzumab and Trastuzumab hyaluronidase (Phesgo) as follows:
- Cycle 5: 1200/600 SC once on day 1
- Cycles 6 to 8: 600/600 SC once on day 1
21-day cycle for 8 cycles
References
- FeDeriCa: Tan AR, Im SA, Mattar A, Colomer R, Stroyakovskii D, Nowecki Z, De Laurentiis M, Pierga JY, Jung KH, Schem C, Hogea A, Badovinac Crnjevic T, Heeson S, Shivhare M, Kirschbrown WP, Restuccia E, Jackisch C; FeDeriCa study group. Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection plus chemotherapy in HER2-positive early breast cancer (FeDeriCa): a randomised, open-label, multicentre, non-inferiority, phase 3 study. Lancet Oncol. 2021 Jan;22(1):85-97. Epub 2020 Dec 21. Erratum in: Lancet Oncol. 2021 Feb;22(2):e42. link to original article PubMed NCT03493854
ddAC-THP (Paclitaxel)
ddAC-THP: dose-dense Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxol (Paclitaxel), Herceptin (Trastuzumab), Pertuzumab
ddAC-PacPH: dose-dense Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Paclitaxel, Pertuzumab, Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Swain et al. 2018 (BERENICE) | 2014-2015 | Phase 2 (RT) | ||
Tan et al. 2021 (FeDeriCa) | 2018-06-14 to 2018-12-24 | Phase 3 (C) | 1a. ddAC-THP (Paclitaxel, Phesgo) 1b. AC-THP (Docetaxel, Phesgo) |
Non-inferior serum trough |
Huober et al. 2022 (IMpassion050) | 2019-01 to 2020-08 | Phase 3 (C) | ddAC-THP & Atezolizumab | Did not meet primary endpoint of pCR rate |
Chemotherapy, ddAC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Supportive therapy, ddAC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, THP portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 8: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 8: 420 mg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 4 cycles
References
- BERENICE: Swain SM, Ewer MS, Viale G, Delaloge S, Ferrero JM, Verrill M, Colomer R, Vieira C, Werner TL, Douthwaite H, Bradley D, Waldron-Lynch M, Kiermaier A, Eng-Wong J, Dang C; BERENICE Study Group. Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): a phase II, open-label, multicenter, multinational cardiac safety study. Ann Oncol. 2018 Mar 1;29(3):646-653. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02132949
- Update: Dang C, Ewer MS, Delaloge S, Ferrero JM, Colomer R, de la Cruz-Merino L, Werner TL, Dadswell K, Verrill M, Eiger D, Sarkar S, de Haas SL, Restuccia E, Swain SM. BERENICE Final Analysis: Cardiac Safety Study of Neoadjuvant Pertuzumab, Trastuzumab, and Chemotherapy Followed by Adjuvant Pertuzumab and Trastuzumab in HER2-Positive Early Breast Cancer. Cancers (Basel). 2022 May 24;14(11):2596. link to original article link to PMC article PubMed
- FeDeriCa: Tan AR, Im SA, Mattar A, Colomer R, Stroyakovskii D, Nowecki Z, De Laurentiis M, Pierga JY, Jung KH, Schem C, Hogea A, Badovinac Crnjevic T, Heeson S, Shivhare M, Kirschbrown WP, Restuccia E, Jackisch C; FeDeriCa study group. Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection plus chemotherapy in HER2-positive early breast cancer (FeDeriCa): a randomised, open-label, multicentre, non-inferiority, phase 3 study. Lancet Oncol. 2021 Jan;22(1):85-97. Epub 2020 Dec 21. Erratum in: Lancet Oncol. 2021 Feb;22(2):e42. link to original article PubMed NCT03493854
- IMpassion050: Huober J, Barrios CH, Niikura N, Jarząb M, Chang YC, Huggins-Puhalla SL, Pedrini J, Zhukova L, Graupner V, Eiger D, Henschel V, Gochitashvili N, Lambertini C, Restuccia E, Zhang H; IMpassion050 Trial Investigators. Atezolizumab With Neoadjuvant Anti-Human Epidermal Growth Factor Receptor 2 Therapy and Chemotherapy in Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: Primary Results of the Randomized Phase III IMpassion050 Trial. J Clin Oncol. 2022 Sep 1;40(25):2946-2956. Epub 2022 Jun 28. link to original article link to PMC article PubMed NCT03726879
ddAC-THP (Paclitaxel, Phesgo)
ddAC-THP (Phesgo): dose-dense Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxol (Paclitaxel) and Phesgo
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tan et al. 2021 (FeDeriCa) | 2018-06-14 to 2018-12-24 | Phase 3 (E-RT-switch-ic) | 1a. ddAC-THP 1b. AC-THP |
Non-inferior serum trough |
Chemotherapy, ddAC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Supportive therapy, ddAC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, THP (Phesgo) portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, THP (Phesgo) portion
- Pertuzumab and Trastuzumab hyaluronidase (Phesgo) as follows:
- Cycle 5: 1200/600 SC once on day 1
- Cycles 6 to 8: 600/600 SC once on day 1
14-day cycle for 4, then 21-day cycle for 4 cycles
References
- FeDeriCa: Tan AR, Im SA, Mattar A, Colomer R, Stroyakovskii D, Nowecki Z, De Laurentiis M, Pierga JY, Jung KH, Schem C, Hogea A, Badovinac Crnjevic T, Heeson S, Shivhare M, Kirschbrown WP, Restuccia E, Jackisch C; FeDeriCa study group. Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection plus chemotherapy in HER2-positive early breast cancer (FeDeriCa): a randomised, open-label, multicentre, non-inferiority, phase 3 study. Lancet Oncol. 2021 Jan;22(1):85-97. Epub 2020 Dec 21. Erratum in: Lancet Oncol. 2021 Feb;22(2):e42. link to original article PubMed NCT03493854
AC-TL (Paclitaxel)
AC-TL: Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxol (Paclitaxel) & Lapatinib
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Robidoux et al. 2013 (NSABP B-41) | 2007-2011 | Phase 3 (E-switch-ic) | 1. AC-TH | Did not meet primary endpoint of pCR rate |
2. AC-THL | Might have inferior pCR rate (primary endpoint) |
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Chemotherapy, TL portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, TL portion (cycles 5 to 8)
- Lapatinib (Tykerb) 1250 mg PO once per day
21-day cycle for 4 cycles, then 28-day cycle for 4 cycles
Subsequent treatment
- Surgery, then adjuvant trastuzumab for a total of 52 weeks of therapy
References
- NSABP B-41: Robidoux A, Tang G, Rastogi P, Geyer CE Jr, Azar CA, Atkins JN, Fehrenbacher L, Bear HD, Baez-Diaz L, Sarwar S, Margolese RG, Farrar WB, Brufsky AM, Shibata HR, Bandos H, Paik S, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1183-92. Epub 2013 Oct 4. link to original article contains dosing details in abstract PubMed NCT00486668
EC-TH (Docetaxel)
EC-TH: Epirubicin & Cyclophosphamide, followed by Taxotere (Docetaxel) & Herceptin (Trastuzumab)
EC-DT: Epirubicin & Cyclophosphamide, followed by Docetaxel & Trastuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Alba et al. 2014 (GEICAM 2006-14) | 2009-2010 | Phase 3 (C) | EC-TL | Superior pCR rate |
Chemotherapy, EC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 5 to 8)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 8: 6 mg/kg IV once on day 1
21-day cycle for 8 cycles
Subsequent treatment
References
- GEICAM 2006-14: Alba E, Albanell J, de la Haba J, Barnadas A, Calvo L, Sánchez-Rovira P, Ramos M, Rojo F, Burgués O, Carrasco E, Caballero R, Porras I, Tibau A, Cámara MC, Lluch A. Trastuzumab or lapatinib with standard chemotherapy for HER2-positive breast cancer: results from the GEICAM/2006-14 trial. Br J Cancer. 2014 Mar 4;110(5):1139-47. Epub 2014 Jan 23. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00841828
ECH-TH (Docetaxel)
ECH-TH: Epirubicin, Cyclophosphamide, Herceptin (Trastuzumab), followed by Taxotere (Docetaxel) & Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Untch et al. 2012 (GeparQuinto) | 2007-2010 | Phase 3 (C) | ECL-TL | Seems to have superior pCR rate |
Chemotherapy, ECH portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Targeted therapy, ECH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 4: 6 mg/kg IV once on day 1
Chemotherapy, TH portion (cycles 5 to 8)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, TH portion (cycles 5 to 8)
- Trastuzumab (Herceptin) 6 mg/kg IV once on day 1
21-day cycle for 8 cycles
Subsequent treatment
- Surgery, then adjuvant trastuzumab for 1 year total
References
- GeparQuinto: Untch M, Loibl S, Bischoff J, Eidtmann H, Kaufmann M, Blohmer JU, Hilfrich J, Strumberg D, Fasching PA, Kreienberg R, Tesch H, Hanusch C, Gerber B, Rezai M, Jackisch C, Huober J, Kühn T, Nekljudova V, von Minckwitz G; German Breast Group; Arbeitsgemeinschaft Gynäkologische Onkologie-Breast Study Group. Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial. Lancet Oncol. 2012 Feb;13(2):135-44. Epub 2012 Jan 17. link to original article contains dosing details in manuscript PubMed NCT00567554
- Update: Untch M, von Minckwitz G, Gerber B, Schem C, Rezai M, Fasching PA, Tesch H, Eggemann H, Hanusch C, Huober J, Solbach C, Jackisch C, Kunz G, Blohmer JU, Hauschild M, Fehm T, Nekljudova V, Loibl S; GBG; AGO-B Study Group. Survival analysis after neoadjuvant chemotherapy with trastuzumab or lapatinib in patients with human epidermal growth factor receptor 2-positive breast cancer in the GeparQuinto (G5) study (GBG 44). J Clin Oncol. 2018 May 1;36(13):1308-1316. Epub 2018 Mar 15. link to original article PubMed
FEC-TH (Paclitaxel)
FEC-TH: Fluorouracil, Epirubicin, Cyclophosphamide, followed by Taxol (Paclitaxel) & Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Buzdar et al. 2013 (ACOSOG Z1041) | 2007-2011 | Phase 3 (C) | TH-FEC & H | Did not meet primary endpoint of pCR |
Chemotherapy, FEC portion (cycles 1 to 4)
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 6 to 8: 2 mg/kg IV once per day on days 1, 8, 15
21-day cycle for 8 cycles
Subsequent treatment
References
- ACOSOG Z1041: Buzdar AU, Suman VJ, Meric-Bernstam F, Leitch AM, Ellis MJ, Boughey JC, Unzeitig G, Royce M, McCall LM, Ewer MS, Hunt KK; American College of Surgeons Oncology Group. Fluorouracil, epirubicin, and cyclophosphamide (FEC-75) followed by paclitaxel plus trastuzumab versus paclitaxel plus trastuzumab followed by FEC-75 plus trastuzumab as neoadjuvant treatment for patients with HER2-positive breast cancer (Z1041): a randomised, controlled, phase 3 trial. Lancet Oncol. 2013 Dec;14(13):1317-25. Epub 2013 Nov 13. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00513292
- Update: Buzdar AU, Suman VJ, Meric-Bernstam F, Leitch AM, Ellis MJ, Boughey JC, Unzeitig GW, Royce ME, Hunt KK. Disease-Free and Overall Survival Among Patients With Operable HER2-Positive Breast Cancer Treated With Sequential vs Concurrent Chemotherapy: The ACOSOG Z1041 (Alliance) Randomized Clinical Trial. JAMA Oncol. 2019 Jan 1;5(1):45-50. link to original article link to PMC article PubMed
FEC-THP (Docetaxel)
FEC-THP: Fluorouracil, Epirubicin, Cyclophosphamide, followed by Taxotere (Docetaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen variant #1, 3 x 3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Schneeweiss et al. 2013 (TRYPHAENA) | 2009-2011 | Randomized Phase 2 (E-RT-switch-ic) | 1. FEC & HP-THP 2. TCHP |
Not reported |
Chemotherapy, FEC portion (cycles 1 to 3)
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Chemotherapy, THP portion
- Docetaxel (Taxotere) as follows:
- Cycle 4: 75 mg/m2 IV once on day 1
- Cycles 5 & 6, if no toxic effects occurred: 100 mg/m2 IV once on day 1
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 4: 8 mg/kg IV once on day 1
- Cycles 5 & 6: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 4: 840 mg IV once on day 1
- Cycles 5 & 6: 420 mg IV once on day 1
21-day cycle for 6 cycles
Subsequent treatment
- Surgery, then further adjuvant treatment (radiotherapy, chemotherapy, hormonal treatment) according to local guidelines (a total of 1 year of trastuzumab was given)
Regimen variant #2, 4 x 4
Study | Dates of enrollment | Evidence |
---|---|---|
Swain et al. 2018 (BERENICE) | 2014-2015 | Phase 2 (RT) |
Chemotherapy, FEC portion (cycles 1 to 4)
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Chemotherapy, THP portion
- Docetaxel (Taxotere) as follows:
- Cycle 5: 75 mg/m2 IV once on day 1
- Cycles 6 to 8, if no toxic effects occurred: 100 mg/m2 IV once on day 1
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 8: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 8: 420 mg IV once on day 1
21-day cycle for 8 cycles
References
- TRYPHAENA: Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, Tausch C, Seo JH, Tsai YF, Ratnayake J, McNally V, Ross G, Cortés J. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013 Sep;24(9):2278-84. Epub 2013 May 22. link to original article contains dosing details in manuscript PubMed NCT00976989
- Update: Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Waldron-Lynch M, Eng-Wong J, Kirk S, Cortés J. Long-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: Evaluating pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer. Eur J Cancer. 2018 Jan;89:27-35. Epub 2017 Dec 8. link to original article PubMed
- BERENICE: Swain SM, Ewer MS, Viale G, Delaloge S, Ferrero JM, Verrill M, Colomer R, Vieira C, Werner TL, Douthwaite H, Bradley D, Waldron-Lynch M, Kiermaier A, Eng-Wong J, Dang C; BERENICE Study Group. Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): a phase II, open-label, multicenter, multinational cardiac safety study. Ann Oncol. 2018 Mar 1;29(3):646-653. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02132949
- Update: Dang C, Ewer MS, Delaloge S, Ferrero JM, Colomer R, de la Cruz-Merino L, Werner TL, Dadswell K, Verrill M, Eiger D, Sarkar S, de Haas SL, Restuccia E, Swain SM. BERENICE Final Analysis: Cardiac Safety Study of Neoadjuvant Pertuzumab, Trastuzumab, and Chemotherapy Followed by Adjuvant Pertuzumab and Trastuzumab in HER2-Positive Early Breast Cancer. Cancers (Basel). 2022 May 24;14(11):2596. link to original article link to PMC article PubMed
Neratinib & Paclitaxel, then AC
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Park et al. 2016 (I-SPY 2 neratinib) | 2010-2013 | Adaptively Randomized Phase 2 (E-switch-ic) | 1. TH-AC 2. TH-ddAC |
Seems to have superior pCR rate (primary endpoint) |
Targeted therapy, neratinib & paclitaxel portion (cycles 1 to 4)
- Neratinib (Nerlynx) 240 mg PO once per day
Chemotherapy, neratinib & paclitaxel portion (cycles 1 to 4)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Supportive therapy, neratinib & paclitaxel portion (cycles 1 to 4)
- Loperamide (Imodium) 4 mg PO once on day 1, then 2 mg PO once 8 hours later, then 2 mg PO twice per day for two weeks, then decreased per patient choice, started on day 1 of neratinib
Chemotherapy, AC portion (cycles 5 to 8)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 8 cycles
Subsequent treatment
References
- I-SPY 2 neratinib: Park JW, Liu MC, Yee D, Yau C, van 't Veer LJ, Symmans WF, Paoloni M, Perlmutter J, Hylton NM, Hogarth M, DeMichele A, Buxton MB, Chien AJ, Wallace AM, Boughey JC, Haddad TC, Chui SY, Kemmer KA, Kaplan HG, Isaacs C, Nanda R, Tripathy D, Albain KS, Edmiston KK, Elias AD, Northfelt DW, Pusztai L, Moulder SL, Lang JE, Viscusi RK, Euhus DM, Haley BB, Khan QJ, Wood WC, Melisko M, Schwab R, Helsten T, Lyandres J, Davis SE, Hirst GL, Sanil A, Esserman LJ, Berry DA; I-SPY 2 Investigators. Adaptive randomization of neratinib in early breast cancer. N Engl J Med. 2016 Jul 7;375(1):11-22. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01042379
Neratinib & Paclitaxel, then ddAC
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Park et al. 2016 (I-SPY 2 neratinib) | 2010-2013 | Adaptively Randomized Phase 2 (E-switch-ic) | 1. TH-AC 2. TH-ddAC |
Seems to have superior pCR rate (primary endpoint) |
Targeted therapy, neratinib & paclitaxel portion (cycles 1 to 4)
- Neratinib (Nerlynx) 240 mg PO once per day
Chemotherapy, neratinib & paclitaxel portion (cycles 1 to 4)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Supportive therapy, neratinib & paclitaxel portion (cycles 1 to 4)
- Loperamide (Imodium) 4 mg PO once on day 1, then 2 mg PO once 8 hours later, then 2 mg PO twice per day for two weeks, then decreased per patient choice, started on day 1 of neratinib
Chemotherapy, ddAC portion (cycles 5 to 8)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Supportive therapy, ddAC portion (cycles 5 to 8)
- Pegfilgrastim (Neulasta) 6 mg SC once on day 2, given 24 hours after chemotherapy
21-day cycle for 4 cycles, then 14-day cycle for 4 cycles
Subsequent treatment
References
- I-SPY 2 neratinib: Park JW, Liu MC, Yee D, Yau C, van 't Veer LJ, Symmans WF, Paoloni M, Perlmutter J, Hylton NM, Hogarth M, DeMichele A, Buxton MB, Chien AJ, Wallace AM, Boughey JC, Haddad TC, Chui SY, Kemmer KA, Kaplan HG, Isaacs C, Nanda R, Tripathy D, Albain KS, Edmiston KK, Elias AD, Northfelt DW, Pusztai L, Moulder SL, Lang JE, Viscusi RK, Euhus DM, Haley BB, Khan QJ, Wood WC, Melisko M, Schwab R, Helsten T, Lyandres J, Davis SE, Hirst GL, Sanil A, Esserman LJ, Berry DA; I-SPY 2 Investigators. Adaptive randomization of neratinib in early breast cancer. N Engl J Med. 2016 Jul 7;375(1):11-22. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01042379
TH-AC (Paclitaxel)
TH-AC: Taxol (Paclitaxel) & Herceptin (Trastuzumab), followed by Adriamycin (Doxorubicin) & Cyclophosphamide
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Park et al. 2016 (I-SPY 2 neratinib) | 2010-2013 | Adaptively Randomized Phase 2 (C) | 1. Neratinib & Paclitaxel, then AC 2. Neratinib & Paclitaxel, then ddAC |
Seems to have inferior pCR rate |
=Chemotherapy, TH portion (cycles 1 to 4)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 2 to 4: 2 mg/kg IV once per day on days 1, 8, 15
Chemotherapy, AC portion (cycles 5 to 8)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 8 cycles
Subsequent treatment
References
- I-SPY 2 neratinib: Park JW, Liu MC, Yee D, Yau C, van 't Veer LJ, Symmans WF, Paoloni M, Perlmutter J, Hylton NM, Hogarth M, DeMichele A, Buxton MB, Chien AJ, Wallace AM, Boughey JC, Haddad TC, Chui SY, Kemmer KA, Kaplan HG, Isaacs C, Nanda R, Tripathy D, Albain KS, Edmiston KK, Elias AD, Northfelt DW, Pusztai L, Moulder SL, Lang JE, Viscusi RK, Euhus DM, Haley BB, Khan QJ, Wood WC, Melisko M, Schwab R, Helsten T, Lyandres J, Davis SE, Hirst GL, Sanil A, Esserman LJ, Berry DA; I-SPY 2 Investigators. Adaptive randomization of neratinib in early breast cancer. N Engl J Med. 2016 Jul 7;375(1):11-22. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01042379
TH-ddAC (Paclitaxel)
TH-ddAC: Taxol (Paclitaxel) & Herceptin (Trastuzumab), followed by dose-dense Adriamycin (Doxorubicin) & Cyclophosphamide
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Park et al. 2016 (I-SPY 2 neratinib) | 2010-2013 | Adaptively Randomized Phase 2 (C) | 1. Neratinib & Paclitaxel, then AC 2. Neratinib & Paclitaxel, then ddAC |
Seems to have inferior pCR rate |
Chemotherapy, TH portion (cycles 1 to 4)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 2 to 4: 2 mg/kg IV once per day on days 1, 8, 15
Chemotherapy, ddAC portion (cycles 5 to 8)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Supportive therapy, ddAC portion (cycles 5 to 8)
- Pegfilgrastim (Neulasta) 6 mg SC once on day 2, given 24 hours after chemotherapy
21-day cycle for 4 cycles, then 14-day cycle for 4 cycles
Subsequent treatment
References
- I-SPY 2 neratinib: Park JW, Liu MC, Yee D, Yau C, van 't Veer LJ, Symmans WF, Paoloni M, Perlmutter J, Hylton NM, Hogarth M, DeMichele A, Buxton MB, Chien AJ, Wallace AM, Boughey JC, Haddad TC, Chui SY, Kemmer KA, Kaplan HG, Isaacs C, Nanda R, Tripathy D, Albain KS, Edmiston KK, Elias AD, Northfelt DW, Pusztai L, Moulder SL, Lang JE, Viscusi RK, Euhus DM, Haley BB, Khan QJ, Wood WC, Melisko M, Schwab R, Helsten T, Lyandres J, Davis SE, Hirst GL, Sanil A, Esserman LJ, Berry DA; I-SPY 2 Investigators. Adaptive randomization of neratinib in early breast cancer. N Engl J Med. 2016 Jul 7;375(1):11-22. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01042379
TH-FEC & H (Docetaxel)
TH-FEC & H: Taxotere (Docetaxel) & Herceptin (Trastuzumab), followed by Fluorouracil, Epirubicin, Cyclophosphamide, Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ismael et al. 2012 (HannaH) | 2009-2010 | Phase 3 (C) | TH-FEC & H (SC) | Non-inferior pCR rate |
Pivot et al. 2018 (SB3-G31-BC) | 2014-04 to 2015-08 | Phase 3 (C) | TH-FEC & H (Biosimilar trastuzumab) | Equivalent pCR rate |
Chemotherapy, T portion (cycles 1 to 4)
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Chemotherapy, FEC portion (cycles 5 to 8)
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
Targeted therapy, both portions
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 8: 6 mg/kg IV once on day 1
21-day cycle for 8 cycles
Subsequent treatment
- HannaH: Surgery
- SB3-G31-BC: Surgery, then adjuvant trastuzumab x 30 wk
References
- HannaH: Ismael G, Hegg R, Muehlbauer S, Heinzmann D, Lum B, Kim SB, Pienkowski T, Lichinitser M, Semiglazov V, Melichar B, Jackisch C. Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I-III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial. Lancet Oncol. 2012 Sep;13(9):869-78. Epub 2012 Aug 9. link to original article contains dosing details in manuscript PubMed NCT00950300
- Update: Jackisch C, Kim SB, Semiglazov V, Melichar B, Pivot X, Hillenbach C, Stroyakovskiy D, Lum BL, Elliott R, Weber HA, Ismael G. Subcutaneous versus intravenous formulation of trastuzumab for HER2-positive early breast cancer: updated results from the phase III HannaH study. Ann Oncol. 2015 Feb;26(2):320-5. Epub 2014 Nov 17. link to original article PubMed
- Update: Jackisch C, Stroyakovskiy D, Pivot X, Ahn JS, Melichar B, Chen SC, Meyenberg C, Al-Sakaff N, Heinzmann D, Hegg R. Subcutaneous vs intravenous trastuzumab for patients with ERBB2-positive early breast cancer: final analysis of the HannaH phase 3 randomized clinical trial. JAMA Oncol. 2019 May 1;5(5):e190339. Epub 2019 May 9. link to original article link to PMC article PubMed
- SB3-G31-BC: Pivot X, Bondarenko I, Nowecki Z, Dvorkin M, Trishkina E, Ahn JH, Vinnyk Y, Im SA, Sarosiek T, Chatterjee S, Wojtukiewicz MZ, Moiseyenko V, Shparyk Y, Bello M 3rd, Semiglazov V, Song S, Lim J. Phase III, randomized, double-blind study comparing the efficacy, safety, and immunogenicity of SB3 (trastuzumab biosimilar) and reference trastuzumab in patients treated with neoadjuvant therapy for human epidermal growth factor receptor 2-positive early breast cancer. J Clin Oncol. 2018 Apr 1;36(10):968-974. Epub 2018 Jan 26. link to original article contains dosing details in manuscript PubMed NCT02149524
TH-FEC & H (Docetaxel, SC Trastuzumab)
TH-FEC & H: Taxotere (Docetaxel) & Herceptin Hylecta (Trastuzumab and hyaluronidase), followed by Fluorouracil, Epirubicin, Cyclophosphamide, Herceptin Hylecta (Trastuzumab and hyaluronidase)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ismael et al. 2012 (HannaH) | 2009-2010 | Phase 3 (E-RT-switch-ic) | TH-FEC & H (IV) | Non-inferior pCR rate (co-primary endpoint) |
Chemotherapy, T portion (cycles 1 to 4)
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Chemotherapy, FEC portion (cycles 5 to 8)
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
Targeted therapy, both portions (cycles 1 to 8)
- Trastuzumab and hyaluronidase (Herceptin Hylecta) 600 mg/10,000 units SC once on day 1
21-day cycle for 8 cycles
Subsequent treatment
References
- HannaH: Ismael G, Hegg R, Muehlbauer S, Heinzmann D, Lum B, Kim SB, Pienkowski T, Lichinitser M, Semiglazov V, Melichar B, Jackisch C. Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I-III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial. Lancet Oncol. 2012 Sep;13(9):869-78. Epub 2012 Aug 9. link to original article contains dosing details in manuscript PubMed NCT00950300
- Update: Jackisch C, Kim SB, Semiglazov V, Melichar B, Pivot X, Hillenbach C, Stroyakovskiy D, Lum BL, Elliott R, Weber HA, Ismael G. Subcutaneous versus intravenous formulation of trastuzumab for HER2-positive early breast cancer: updated results from the phase III HannaH study. Ann Oncol. 2015 Feb;26(2):320-5. Epub 2014 Nov 17. link to original article PubMed
- Update: Jackisch C, Stroyakovskiy D, Pivot X, Ahn JS, Melichar B, Chen SC, Meyenberg C, Al-Sakaff N, Heinzmann D, Hegg R. Subcutaneous vs intravenous trastuzumab for patients with ERBB2-positive early breast cancer: final analysis of the HannaH phase 3 randomized clinical trial. JAMA Oncol. 2019 May 1;5(5):e190339. Epub 2019 May 9. link to original article link to PMC article PubMed
TH-FEC & H (Paclitaxel)
TH-FEC & H: Taxol (Paclitaxel) & Herceptin (Trastuzumab), followed by Fluorouracil, Epirubicin, Cyclophosphamide, Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Buzdar et al. 2005 | 2001-2003 | Phase 3 (E-esc) | T-FEC | Seems to have superior pCR rate (primary endpoint) |
Chemotherapy, T portion (cycles 1 to 4)
- Paclitaxel (Taxol) 225 mg/m2 IV continuous infusion over 24 hours, started on day 1
Chemotherapy, FEC portion (cycles 5 to 8)
- Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 & 4
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
Targeted therapy, both portions
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, given prior to first dose of paclitaxel, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 2 to 8: 2 mg/kg IV once per day on days 1, 8, 15
21-day cycle for 8 cycles
Subsequent treatment
References
- Buzdar AU, Ibrahim NK, Francis D, Booser DJ, Thomas ES, Theriault RL, Pusztai L, Green MC, Arun BK, Giordano SH, Cristofanilli M, Frye DK, Smith TL, Hunt KK, Singletary SE, Sahin AA, Ewer MS, Buchholz TA, Berry D, Hortobagyi GN. Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol. 2005 Jun 1;23(16):3676-85. Epub 2005 Feb 28. link to original article contains dosing details in manuscript PubMed
- Update: Buzdar AU, Valero V, Ibrahim NK, Francis D, Broglio KR, Theriault RL, Pusztai L, Green MC, Singletary SE, Hunt KK, Sahin AA, Esteva F, Symmans WF, Ewer MS, Buchholz TA, Hortobagyi GN. Neoadjuvant therapy with paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide chemotherapy and concurrent trastuzumab in human epidermal growth factor receptor 2-positive operable breast cancer: an update of the initial randomized study population and data of additional patients treated with the same regimen. Clin Cancer Res. 2007 Jan 1;13(1):228-33. link to original article PubMed
Neoadjuvant therapy
Lapatinib & Trastuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Baselga et al. 2012 (NeoALTTO) | 2008-2010 | Phase 3 (E-esc) | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Targeted therapy
- Lapatinib (Tykerb) 1000 mg PO once per day
- Trastuzumab (Herceptin) 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22, 29, 36
6-week course
Subsequent treatment
- THL (Taxol) x 12 wk, then surgery
References
- NeoALTTO: Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00553358
- Update: de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. Epub 2014 Aug 14. link to original article PubMed
- Update: Huober J, Holmes E, Baselga J, de Azambuja E, Untch M, Fumagalli D, Sarp S, Lang I, Smith I, Boyle F, Xu B, Lecocq C, Wildiers H, Jouannaud C, Hackman J, Dasappa L, Ciruelos E, Toral Pena JC, Adamchuk H, Hickish T, de la Pena L, Jackisch C, Gelber RD, Piccart-Gebhart M, Di Cosimo S. Survival outcomes of the NeoALTTO study (BIG 1-06): updated results of a randomised multicenter phase III neoadjuvant clinical trial in patients with HER2-positive primary breast cancer. Eur J Cancer. 2019 Sep;118:169-177. Epub 2019 Aug 1. link to original article PubMed
TCHP (Paclitaxel)
TCHP: Taxol (Paclitaxel), Carboplatin, Herceptin (Trastuzumab), Pertuzumab
Regimen variant #1, standard carboplatin
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
van Ramshorst et al. 2018 (TRAIN-2) | 2013-2016 | Phase 3 (E-switch-ic) | FEC & HP x 3, then TCHP x 6 | Did not meet primary endpoint of pCR rate |
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1 & 8
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 9: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycles 2 to 9: 420 mg IV once on day 1
21-day cycle for 9 cycles
Subsequent treatment
Regimen variant #2, split carboplatin
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
van Ramshorst et al. 2018 (TRAIN-2) | 2013-2016 | Phase 3 (E-switch-ic) | FEC & HP x 3, then TCHP x 6 | Did not meet primary endpoint of pCR rate |
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1 & 8
- Carboplatin (Paraplatin) AUC 3 IV once per day on days 1 & 8
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 9: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycles 2 to 9: 420 mg IV once on day 1
21-day cycle for 9 cycles
Subsequent treatment
References
- TRAIN-2: van Ramshorst MS, van der Voort A, van Werkhoven ED, Mandjes IA, Kemper I, Dezentjé VO, Oving IM, Honkoop AH, Tick LW, van de Wouw AJ, Mandigers CM, van Warmerdam LJ, Wesseling J, Vrancken Peeters MT, Linn SC, Sonke GS; Dutch Breast Cancer Research Group. Neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2 blockade for HER2-positive breast cancer (TRAIN-2): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2018 Dec;19(12):1630-1640. Epub 2018 Nov 6. link to original article contains dosing details in abstract PubMed NCT01996267
- Update: van der Voort A, van Ramshorst MS, van Werkhoven ED, Mandjes IA, Kemper I, Vulink AJ, Oving IM, Honkoop AH, Tick LW, van de Wouw AJ, Mandigers CM, van Warmerdam LJ, Wesseling J, Vrancken Peeters MT, Linn SC, Sonke GS. Three-Year Follow-up of Neoadjuvant Chemotherapy With or Without Anthracyclines in the Presence of Dual ERBB2 Blockade in Patients With ERBB2-Positive Breast Cancer: A Secondary Analysis of the TRAIN-2 Randomized, Phase 3 Trial. JAMA Oncol. 2021 Jul 1;7(7):978-984. link to original article link to PMC article PubMed
TCHP (Docetaxel)
TCHP: Taxotere (Docetaxel), Carboplatin, Herceptin (Trastuzumab), Pertuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Schneeweiss et al. 2013 (TRYPHAENA) | 2009-2011 | Randomized Phase 2 (E-RT-switch-ic) | 1. FEC-THP 2. FEC & HP-THP |
Not reported |
Hurvitz et al. 2017 (KRISTINE) | 2014-2015 | Phase 3 (C) | Pertuzumab & T-DM1 | Superior EFS1 (HR 0.38, 95% CI 0.20-0.74) |
1Reported efficacy for KRISTINE is based on the 2019 update. EFS was a secondary endpoint.
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 6: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycles 2 to 6: 420 mg IV once on day 1
21-day cycle for 6 cycles
References
- TRYPHAENA: Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, Tausch C, Seo JH, Tsai YF, Ratnayake J, McNally V, Ross G, Cortés J. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013 Sep;24(9):2278-84. Epub 2013 May 22. link to original article contains dosing details in manuscript PubMed NCT00976989
- Update: Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Waldron-Lynch M, Eng-Wong J, Kirk S, Cortés J. Long-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: Evaluating pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer. Eur J Cancer. 2018 Jan;89:27-35. Epub 2017 Dec 8. link to original article PubMed
- KRISTINE: Hurvitz SA, Martin M, Symmans WF, Jung KH, Huang CS, Thompson AM, Harbeck N, Valero V, Stroyakovskiy D, Wildiers H, Campone M, Boileau JF, Beckmann MW, Afenjar K, Fresco R, Helms HJ, Xu J, Lin YG, Sparano J, Slamon D. Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2018 Jan;19(1):115-126. Epub 2017 Nov 23. link to original article contains dosing details in abstract PubMed NCT02131064
- Update: Hurvitz SA, Martin M, Jung KH, Huang CS, Harbeck N, Valero V, Stroyakovskiy D, Wildiers H, Campone M, Boileau JF, Fasching PA, Afenjar K, Spera G, Lopez-Valverde V, Song C, Trask P, Boulet T, Sparano JA, Symmans WF, Thompson AM, Slamon D. Neoadjuvant trastuzumab emtansine and pertuzumab in human epidermal growth factor receptor 2-positive breast cancer: three-year outcomes from the phase III KRISTINE Study. J Clin Oncol. 2019 Sep 1;37(25):2206-2216. Epub 2019 Jun 3. link to original article link to PMC article PubMed
Paclitaxel & Trastuzumab (TH)
TH: Taxol (Paclitaxel) & Herceptin (Trastuzumab)
T-T: Taxol (Paclitaxel) & Trastuzumab
Regimen variant #1, weekly paclitaxel x 12, weekly trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Baselga et al. 2012 (NeoALTTO) | 2008-2010 | Phase 3 (C) | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. Patients in NeoALTTO had already undergone trastuzumab loading so would continue at the 2 mg/kg weekly dose.
Preceding treatment
- NeoALTTO: Trastuzumab x 6 wk
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 2 to 4: 2 mg/kg IV once per day on days 1, 8, 15
21-day cycle for 4 cycles
Regimen variant #2, weekly paclitaxel x 12, q3wk trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2018 (LILAC) | 2013-2015 | Phase 3 (C) | Paclitaxel & Trastuzumab-anns | Inconclusive whether equivalent pCR rate |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 4: 6 mg/kg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
Regimen variant #3, weekly paclitaxel x 16
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Carey et al. 2015 (CALGB 40601) | 2008-2012 | Phase 3 (C) | 1. THL | Did not meet primary endpoint of pCR rate |
2. TL | Not reported |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15, 22
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22
- Cycles 2 to 4: 2 mg/kg IV once per day on days 1, 8, 15, 22
28-day cycle for 4 cycles
Subsequent treatment
- Surgery, then adjuvant AC x 4 or ddAC x 4, then trastuzumab for 36 weeks was recommended but not mandated
Regimen variant #4, q3wk, paclitaxel 175 mg/m2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2018 (LILAC) | 2013-2015 | Phase 3 (C) | Paclitaxel & Trastuzumab-anns | Inconclusive whether equivalent pCR rate |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once
- Cycles 2 to 4: 6 mg/kg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
References
- NeoALTTO: Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00553358
- Update: de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. Epub 2014 Aug 14. link to original article PubMed
- Update: Huober J, Holmes E, Baselga J, de Azambuja E, Untch M, Fumagalli D, Sarp S, Lang I, Smith I, Boyle F, Xu B, Lecocq C, Wildiers H, Jouannaud C, Hackman J, Dasappa L, Ciruelos E, Toral Pena JC, Adamchuk H, Hickish T, de la Pena L, Jackisch C, Gelber RD, Piccart-Gebhart M, Di Cosimo S. Survival outcomes of the NeoALTTO study (BIG 1-06): updated results of a randomised multicenter phase III neoadjuvant clinical trial in patients with HER2-positive primary breast cancer. Eur J Cancer. 2019 Sep;118:169-177. Epub 2019 Aug 1. link to original article PubMed
- CALGB 40601: Carey LA, Berry DA, Cirrincione CT, Barry WT, Pitcher BN, Harris LN, Ollila DW, Krop IE, Henry NL, Weckstein DJ, Anders CK, Singh B, Hoadley KA, Iglesia M, Cheang MC, Perou CM, Winer EP, Hudis CA. Molecular heterogeneity and response to neoadjuvant human epidermal growth factor receptor 2 targeting in CALGB 40601, a randomized phase III trial of paclitaxel plus trastuzumab with or without lapatinib. J Clin Oncol. 2016 Feb 20;34(6):542-9. Epub 2015 Nov 2. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00770809
- Update: Fernandez-Martinez A, Krop IE, Hillman DW, Polley MY, Parker JS, Huebner L, Hoadley KA, Shepherd J, Tolaney S, Henry NL, Dang C, Harris L, Berry D, Hahn O, Hudis C, Winer E, Partridge A, Perou CM, Carey LA. Survival, Pathologic Response, and Genomics in CALGB 40601 (Alliance), a Neoadjuvant Phase III Trial of Paclitaxel-Trastuzumab With or Without Lapatinib in HER2-Positive Breast Cancer. J Clin Oncol. 2020 Dec 10;38(35):4184-4193. Epub 2020 Oct 23. link to original article link to PMC article PubMed
- I-SPY 2 neratinib: Park JW, Liu MC, Yee D, Yau C, van 't Veer LJ, Symmans WF, Paoloni M, Perlmutter J, Hylton NM, Hogarth M, DeMichele A, Buxton MB, Chien AJ, Wallace AM, Boughey JC, Haddad TC, Chui SY, Kemmer KA, Kaplan HG, Isaacs C, Nanda R, Tripathy D, Albain KS, Edmiston KK, Elias AD, Northfelt DW, Pusztai L, Moulder SL, Lang JE, Viscusi RK, Euhus DM, Haley BB, Khan QJ, Wood WC, Melisko M, Schwab R, Helsten T, Lyandres J, Davis SE, Hirst GL, Sanil A, Esserman LJ, Berry DA; I-SPY 2 Investigators. Adaptive randomization of neratinib in early breast cancer. N Engl J Med. 2016 Jul 7;375(1):11-22. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01042379
- LILAC: von Minckwitz G, Colleoni M, Kolberg HC, Morales S, Santi P, Tomasevic Z, Zhang N, Hanes V. Efficacy and safety of ABP 980 compared with reference trastuzumab in women with HER2-positive early breast cancer (LILAC study): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2018 Jul;19(7):987-998.Epub 2018 Jun 4. link to original article contains dosing details in abstract PubMed NCT01901146
Docetaxel & Trastuzumab (TH)
TH: Taxotere (Docetaxel) & Herceptin (Trastuzumab)
DH: Docetaxel & Herceptin (Trastuzumab)
Regimen variant #1, q3wk docetaxel/trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wu et al. 2022 (PHEDRA) | 2018-2021 | Phase 3 (C) | TH & Pyrotinib | Inferior tpCR rate |
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 4: 6 mg/kg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
Regimen variant #2, 100 mg/m2 q3wk docetaxel, weekly trastuzumab
Study | Dates of enrollment | Evidence | Efficacy |
---|---|---|---|
Van Pelt et al. 2003 | 2000-2002 | Phase 2 | OCR: 77% |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Chemotherapy
- Docetaxel (Taxotere) as follows:
- Cycles 2 to 5: 100 mg/m2 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 2 to 5: 2 mg/kg IV once per day on days 1, 8, 15
21-day cycle for 5 cycles
References
- Van Pelt AE, Mohsin S, Elledge RM, Hilsenbeck SG, Gutierrez MC, Lucci A Jr, Kalidas M, Granchi T, Scott BG, Allred DC, Chang JC. Neoadjuvant trastuzumab and docetaxel in breast cancer: preliminary results. Clin Breast Cancer. 2003 Dec;4(5):348-53. link to original article contains dosing details in abstract PubMed
- PHEDRA: Wu J, Jiang Z, Liu Z, Yang B, Yang H, Tang J, Wang K, Liu Y, Wang H, Fu P, Zhang S, Liu Q, Wang S, Huang J, Wang C, Wang S, Wang Y, Zhen L, Zhu X, Wu F, Lin X, Zou J. Neoadjuvant pyrotinib, trastuzumab, and docetaxel for HER2-positive breast cancer (PHEDRA): a double-blind, randomized phase 3 trial. BMC Med. 2022 Dec 27;20(1):498. link to original article contains dosing details in abstract link to PMC article PubMed NCT03588091
Docetaxel & Trastuzumab (TH) & Pyrotinib
TH & Pyrotinib: Taxotere (Docetaxel), Herceptin (Trastuzumab), Pyrotinib
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wu et al. 2022 (PHEDRA) | 2018-2021 | Phase 3 (E-esc) | TH | Superior tpCR rate (primary endpoint) tpCR rate: 41% vs 22% |
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy
- Pyrotinib (Irene) 400 mg PO once per day
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 4: 6 mg/kg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
References
- PHEDRA: Wu J, Jiang Z, Liu Z, Yang B, Yang H, Tang J, Wang K, Liu Y, Wang H, Fu P, Zhang S, Liu Q, Wang S, Huang J, Wang C, Wang S, Wang Y, Zhen L, Zhu X, Wu F, Lin X, Zou J. Neoadjuvant pyrotinib, trastuzumab, and docetaxel for HER2-positive breast cancer (PHEDRA): a double-blind, randomized phase 3 trial. BMC Med. 2022 Dec 27;20(1):498. link to original article contains dosing details in abstract link to PMC article PubMed NCT03588091
THL (Paclitaxel)
THL: Taxol (Paclitaxel), Herceptin (Trastuzumab), Lapatinib
Regimen variant #1, weekly paclitaxel x 12
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Baselga et al. 2012 (NeoALTTO) | 2008-2010 | Phase 3 (E-esc) | See link | See link |
Preceding treatment
- Lapatinib & Trastuzumab x 6 wk
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15, 22
Targeted therapy
- Trastuzumab (Herceptin) 2 mg/kg IV once per day on days 1, 8, 15, 22
- Lapatinib (Tykerb) 1000 mg PO once per day
28-day cycle for 3 cycles
Regimen variant #2, weekly paclitaxel x 16
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Carey et al. 2015 (CALGB 40601) | 2008-2012 | Phase 3 (E-esc) | 1. TH | Did not meet primary endpoint of pCR rate |
2. TL | Not reported |
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15, 22
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22
- Cycles 2 to 4: 2 mg/kg IV once per day on days 1, 8, 15, 22
- Lapatinib (Tykerb) 750 mg PO once per day
28-day cycle for 4 cycles
Subsequent treatment
- Surgery; adjuvant AC x 4 or ddAC x 4, then trastuzumab for 36 weeks was recommended but not mandated
References
- NeoALTTO: Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00553358
- Update: de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. Epub 2014 Aug 14. link to original article PubMed
- Update: Huober J, Holmes E, Baselga J, de Azambuja E, Untch M, Fumagalli D, Sarp S, Lang I, Smith I, Boyle F, Xu B, Lecocq C, Wildiers H, Jouannaud C, Hackman J, Dasappa L, Ciruelos E, Toral Pena JC, Adamchuk H, Hickish T, de la Pena L, Jackisch C, Gelber RD, Piccart-Gebhart M, Di Cosimo S. Survival outcomes of the NeoALTTO study (BIG 1-06): updated results of a randomised multicenter phase III neoadjuvant clinical trial in patients with HER2-positive primary breast cancer. Eur J Cancer. 2019 Sep;118:169-177. Epub 2019 Aug 1. link to original article PubMed
- CALGB 40601: Carey LA, Berry DA, Cirrincione CT, Barry WT, Pitcher BN, Harris LN, Ollila DW, Krop IE, Henry NL, Weckstein DJ, Anders CK, Singh B, Hoadley KA, Iglesia M, Cheang MC, Perou CM, Winer EP, Hudis CA. Molecular heterogeneity and response to neoadjuvant human epidermal growth factor receptor 2 targeting in CALGB 40601, a randomized phase III trial of paclitaxel plus trastuzumab with or without lapatinib. J Clin Oncol. 2016 Feb 20;34(6):542-9. Epub 2015 Nov 2. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00770809
- Update: Fernandez-Martinez A, Krop IE, Hillman DW, Polley MY, Parker JS, Huebner L, Hoadley KA, Shepherd J, Tolaney S, Henry NL, Dang C, Harris L, Berry D, Hahn O, Hudis C, Winer E, Partridge A, Perou CM, Carey LA. Survival, Pathologic Response, and Genomics in CALGB 40601 (Alliance), a Neoadjuvant Phase III Trial of Paclitaxel-Trastuzumab With or Without Lapatinib in HER2-Positive Breast Cancer. J Clin Oncol. 2020 Dec 10;38(35):4184-4193. Epub 2020 Oct 23. link to original article link to PMC article PubMed
THP (Docetaxel)
THP: Taxotere (Docetaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gianni et al. 2011 (NeoSphere) | 2007-2009 | Randomized Phase 2 (E-RT-esc) | 1. Docetaxel & Pertuzumab | Did not meet primary endpoint of pCR rate |
2. Pertuzumab & Trastuzumab | Did not meet primary endpoint of pCR rate | |||
3. TH | Seems to have superior pCR rate | |||
Shao et al. 2020 (PEONY) | 2016-03-14 to 2017-03-13 | Phase 3 (E-esc) | TH | Superior pCR rate (primary endpoint) |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- Based on tolerability, investigators could increase dose 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
- Cycles 2 to 4: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycles 2 to 4: 420 mg IV once on day 1
21-day cycle for 4 cycles
References
- NeoSphere: Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, Lluch A, Staroslawska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi G, Szado T, Ratnayake J, Ross G, Valagussa P. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012 Jan;13(1):25-32. Epub 2011 Dec 6. link to original article contains dosing details in manuscript PubMed NCT00545688
- Update: Gianni L, Pienkowski T, Im YH, Tseng LM, Liu MC, Lluch A, Starosławska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi GV, Magazzù D, McNally V, Douthwaite H, Ross G, Valagussa P. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 2016 Jun;17(6):791-800. Epub 2016 May 11. link to original article PubMed
- PEONY: Shao Z, Pang D, Yang H, Li W, Wang S, Cui S, Liao N, Wang Y, Wang C, Chang YC, Wang H, Kang SY, Seo JH, Shen K, Laohawiriyakamol S, Jiang Z, Li J, Zhou J, Althaus B, Mao Y, Eng-Wong J. Efficacy, Safety, and Tolerability of Pertuzumab, Trastuzumab, and Docetaxel for Patients With Early or Locally Advanced ERBB2-Positive Breast Cancer in Asia: The PEONY Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Mar 1;6(3):e193692. Epub 2020 Mar 12. link to original article link to PMC article contains dosing details in abstract PubMed NCT02586025
Lapatinib & Paclitaxel (TL)
TL: Taxol (Paclitaxel) & Lapatinib
Regimen variant #1, weekly paclitaxel x 12
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Baselga et al. 2012 (NeoALTTO) | 2008-2010 | Phase 3 (E-switch-ic) | See link | See link |
Preceding treatment
- Lapatinib x 6 wk
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15, 22
Targeted therapy
- Lapatinib (Tykerb) 1500 mg PO once per day
28-day cycle for 3 cycles
Regimen variant #2, weekly paclitaxel x 16
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Carey et al. 2015 (CALGB 40601) | 2008-2012 | Phase 3 (E-switch-ic) | 1. TH | Not reported |
2. THL | Not reported |
Note: this arm was closed early.
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15, 22
Targeted therapy
- Lapatinib (Tykerb) 1500 mg PO once per day
28-day cycle for 4 cycles
Subsequent treatment
- Surgery; adjuvant AC x 4 or ddAC x 4, then trastuzumab for 36 weeks was recommended but not mandated
References
- NeoALTTO: Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00553358
- Update: de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. Epub 2014 Aug 14. link to original article PubMed
- Update: Huober J, Holmes E, Baselga J, de Azambuja E, Untch M, Fumagalli D, Sarp S, Lang I, Smith I, Boyle F, Xu B, Lecocq C, Wildiers H, Jouannaud C, Hackman J, Dasappa L, Ciruelos E, Toral Pena JC, Adamchuk H, Hickish T, de la Pena L, Jackisch C, Gelber RD, Piccart-Gebhart M, Di Cosimo S. Survival outcomes of the NeoALTTO study (BIG 1-06): updated results of a randomised multicenter phase III neoadjuvant clinical trial in patients with HER2-positive primary breast cancer. Eur J Cancer. 2019 Sep;118:169-177. Epub 2019 Aug 1. link to original article PubMed
- CALGB 40601: Carey LA, Berry DA, Cirrincione CT, Barry WT, Pitcher BN, Harris LN, Ollila DW, Krop IE, Henry NL, Weckstein DJ, Anders CK, Singh B, Hoadley KA, Iglesia M, Cheang MC, Perou CM, Winer EP, Hudis CA. Molecular heterogeneity and response to neoadjuvant human epidermal growth factor receptor 2 targeting in CALGB 40601, a randomized phase III trial of paclitaxel plus trastuzumab with or without lapatinib. J Clin Oncol. 2016 Feb 20;34(6):542-9. Epub 2015 Nov 2. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00770809
- Update: Fernandez-Martinez A, Krop IE, Hillman DW, Polley MY, Parker JS, Huebner L, Hoadley KA, Shepherd J, Tolaney S, Henry NL, Dang C, Harris L, Berry D, Hahn O, Hudis C, Winer E, Partridge A, Perou CM, Carey LA. Survival, Pathologic Response, and Genomics in CALGB 40601 (Alliance), a Neoadjuvant Phase III Trial of Paclitaxel-Trastuzumab With or Without Lapatinib in HER2-Positive Breast Cancer. J Clin Oncol. 2020 Dec 10;38(35):4184-4193. Epub 2020 Oct 23. link to original article link to PMC article PubMed
Trastuzumab monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Baselga et al. 2012 (NeoALTTO) | 2008-2010 | Phase 3 (C) | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Targeted therapy
- Trastuzumab (Herceptin) 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22, 29, 36
6-week course
Subsequent treatment
- TH (Paclitaxel) x 12 wk, then surgery
References
- NeoALTTO: Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00553358
- Update: de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. Epub 2014 Aug 14. link to original article PubMed
- Update: Huober J, Holmes E, Baselga J, de Azambuja E, Untch M, Fumagalli D, Sarp S, Lang I, Smith I, Boyle F, Xu B, Lecocq C, Wildiers H, Jouannaud C, Hackman J, Dasappa L, Ciruelos E, Toral Pena JC, Adamchuk H, Hickish T, de la Pena L, Jackisch C, Gelber RD, Piccart-Gebhart M, Di Cosimo S. Survival outcomes of the NeoALTTO study (BIG 1-06): updated results of a randomised multicenter phase III neoadjuvant clinical trial in patients with HER2-positive primary breast cancer. Eur J Cancer. 2019 Sep;118:169-177. Epub 2019 Aug 1. link to original article PubMed
Neoadjuvant response criteria
Clinical response rate (cRR)
Although fairly dated, some trials such as ACOSOG Z1031 make use of the WHO criteria for response to neoadjuvant therapy. Included here primarily for historical purposes.
References
- Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer. 1981 Jan 1;47(1):207-14. link to original article PubMed
Miller-Payne scoring system
- Grade 1: No change or some changes to individual malignant cells, but no reduction in overall cellularity
- Grade 2: Minor loss of tumor cells (up to 30%), but overall cellularity still high
- Grade 3: An estimated 30 to 90% reduction in the number of tumor cells
- Grade 4: Marked disappearance of tumor cells such that only small clusters or widely dispersed individual cells remain (loss of greater than 90% of tumor cells)
- Grade 5: No invasive cancer cells identifiable in sections from the site of the tumor (carcinoma in situ may be present)
References
- Ogston KN, Miller ID, Payne S, Hutcheon AW, Sarkar TK, Smith I, Schofield A, Heys SD. A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast. 2003 Oct;12(5):320-7. link to original article PubMed
Residual cancer burden (RCB)
- The RCB is calculated as follows: RCB = 1.4 (finv*dprim)0.17 + [4(1 - 0.75LN)dmet]0.17
- where dprim is derived from the bidimensional diameters of the primary tumor bed in the resected specimen, finv is the proportion of the primary tumor bed that contains invasive carcinoma, LN is the number of axillary lymph nodes containing metastatic carcinoma, and dmet is the diameter of the largest metastasis in an axillary lymph node.
- The cut-off points are 1.36 and 3.28.
References
- Symmans WF, Peintinger F, Hatzis C, Rajan R, Kuerer H, Valero V, Assad L, Poniecka A, Hennessy B, Green M, Buzdar AU, Singletary SE, Hortobagyi GN, Pusztai L. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol. 2007 Oct 1;25(28):4414-22. Epub 2007 Sep 4. link to original article PubMed
Residual disease in breast and nodes (RDBN)
- Level 1: pCR in breast and nodes with or without in situ carcinoma
- Levels 2 to 4: Residual disease, calculated as 0.2 (residual breast tumor size in cm) + index of involved nodes (0 for no positive nodes, 1 for 1 to 4 positive nodes, 2 for 5 to 7 positive nodes, and 3 for 8 positive nodes) + the Scarff–Bloom–Richardson grade (1, 2, or 3). The cut-off points are 3 and 4.3.
References
- Chollet P, Abrial C, Durando X, Thivat E, Tacca O, Mouret-Reynier MA, Leheurteur M, Kwiatkowski F, Dauplat J, Penault-Llorca F. A new prognostic classification after primary chemotherapy for breast cancer: residual disease in breast and nodes (RDBN). Cancer J. 2008 Mar-Apr;14(2):128-32. link to original article PubMed
Sataloff's classification
- Breast:
- T-A: Total or nearly total therapeutic effect
- T-B: Greater than 50% therapeutic effect
- T-C: Less than 50% therapeutic effect
- T-D: No therapeutic effect
- Lymph node:
- N-A: Therapeutic effect but no metastasis
- N-B: No metastasis, no therapeutic effect
- N-C: Therapeutic effect but metastasis
- N-D: Metastasis, no therapeutic effect
References
- Sataloff DM, Mason BA, Prestipino AJ, Seinige UL, Lieber CP, Baloch Z. Pathologic response to induction chemotherapy in locally advanced carcinoma of the breast: a determinant of outcome. J Am Coll Surg. 1995 Mar;180(3):297-306. PubMed
Tumor response ratio
Calculated as follows: Residual breast disease observed upon pathologic examination divided by the size of the tumor on the pre-neoadjuvant therapy image.
- TRR = 0: pathologic complete response (pCR)
- TRR greater than 0 up to 0.4: strong partial response
- TRR greater than 0.4 up to 1.0: weak partial response (WPR)
- TRR greater than 1.0: tumor growth
References
- Miller M, Ottesen RA, Niland JC, Kruper L, Chen SL, Vito C. Tumor response ratio predicts overall survival in breast cancer patients treated with neoadjuvant chemotherapy. Ann Surg Oncol. 2014 Oct;21(10):3317-23. Epub 2014 Jul 25. link to original article PubMed
ypTNM staging
This system is proprietary to the AJCC. Please visit their site or consult the AJCC Manual for further details.
Adjuvant therapy, sequential regimens
AC-H
AC-H: Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Van Pelt et al. 2003 | 2000-2002 | Phase 2 |
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Targeted therapy, H portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22
- Cycles 6 to 17: 2 mg/kg IV once per day on days 1, 8, 15, 22
21-day cycle for 4 cycles, then 28-day cycle for 13 cycles
References
- Van Pelt AE, Mohsin S, Elledge RM, Hilsenbeck SG, Gutierrez MC, Lucci A Jr, Kalidas M, Granchi T, Scott BG, Allred DC, Chang JC. Neoadjuvant trastuzumab and docetaxel in breast cancer: preliminary results. Clin Breast Cancer. 2003 Dec;4(5):348-53. link to original article PubMed
- RESPECT: Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. link to original article PubMed NCT01104935
AC-TH (Paclitaxel)
AC-TH: Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxol (Paclitaxel) & Herceptin (Trastuzumab)
Regimen variant #1, weekly paclitaxel, q3wk trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for AC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
21-day cycle for 22 cycles
Regimen variant #2, weekly paclitaxel, weekly trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Romond et al. 2005 (NCCTG N9831) | 2000-2005 | Phase 3 (E-RT-esc) | 1. AC-T; weekly paclitaxel | Superior OS1 (secondary endpoint) OS120: 84% vs 75.2% (HR 0.63, 95% CI 0.5-0.73) |
2. AC-T-H | Might have superior DFS2 (primary endpoint) |
1Reported efficacy is based on the 2014 pooled update.
2Reported efficacy is based on the 2011 update.
Preceding treatment
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 6 to 22: 2 mg/kg IV once per day on days 1, 8, 15
21-day cycle for 22 cycles
Regimen variant #3, q3wk paclitaxel, weekly trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Romond et al. 2005 (NSABP B-31) | 2000-2005 | Phase 3 (E-RT-esc) | 1. AC-T; weekly paclitaxel 2. AC-T; q3wk paclitaxel |
Superior OS1 (secondary endpoint) OS120: 84% vs 75.2% (HR 0.63, 95% CI 0.5-0.73) |
Might have superior DASI score |
1Reported efficacy is based on the 2014 pooled update.
Preceding treatment
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 5 to 8)
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 6 to 22: 2 mg/kg IV once per day on days 1, 8, 15
21-day cycle for 22 cycles
References
- NSABP B-31: Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1673-84. link to original article PubMed NCT00004067
- Pooled update: Perez EA, Romond EH, Suman VJ, Jeong JH, Davidson NE, Geyer CE Jr, Martino S, Mamounas EP, Kaufman PA, Wolmark N. Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31. J Clin Oncol. 2011 Sep 1;29(25):3366-73. Epub 2011 Jul 18. link to original article link to PMC article PubMed
- Pooled update: Perez EA, Romond EH, Suman VJ, Jeong JH, Sledge G, Geyer CE Jr, Martino S, Rastogi P, Gralow J, Swain SM, Winer EP, Colon-Otero G, Davidson NE, Mamounas E, Zujewski JA, Wolmark N. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 2014 Nov 20;32(33):3744-52. link to original article link to PMC article PubMed
- HRQoL analysis: Ganz PA, Romond EH, Cecchini RS, Rastogi P, Geyer CE Jr, Swain SM, Jeong JH, Fehrenbacher L, Gross HM, Brufsky AM, Flynn PJ, Wahl TA, Seay TE, Wade JL 3rd, Biggs DD, Atkins JN, Polikoff J, Zapas JL, Mamounas EP, Wolmark N. Long-term follow-up of cardiac function and quality of life for patients in NSABP protocol B-31/NRG Oncology: a randomized trial comparing the safety and efficacy of doxorubicin and cyclophosphamide (AC) followed by paclitaxel with AC followed by paclitaxel and trastuzumab in patients with node-positive breast cancer with tumors overexpressing human epidermal growth factor receptor 2. J Clin Oncol. 2017 Dec 10;35(35):3942-3948. Epub 2017 Oct 26. link to original article link to PMC article PubMed
- NCCTG N9831: Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1673-84. link to original article PubMed NCT00005970
- Pooled update: Perez EA, Romond EH, Suman VJ, Jeong JH, Davidson NE, Geyer CE Jr, Martino S, Mamounas EP, Kaufman PA, Wolmark N. Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31. J Clin Oncol. 2011 Sep 1;29(25):3366-73. Epub 2011 Jul 18. link to original article link to PMC article PubMed
- Update: Perez EA, Suman VJ, Davidson NE, Gralow JR, Kaufman PA, Visscher DW, Chen B, Ingle JN, Dakhil SR, Zujewski J, Moreno-Aspitia A, Pisansky TM, Jenkins RB. Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer. J Clin Oncol. 2011 Dec 1;29(34):4491-7. Epub 2011 Oct 31. link to original article link to PMC article PubMed
- Pooled update: Perez EA, Romond EH, Suman VJ, Jeong JH, Sledge G, Geyer CE Jr, Martino S, Rastogi P, Gralow J, Swain SM, Winer EP, Colon-Otero G, Davidson NE, Mamounas E, Zujewski JA, Wolmark N. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 2014 Nov 20;32(33):3744-52. link to original article link to PMC article PubMed
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains dosing details in supplement link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
ddAC-ddTH (Paclitaxel)
ddAC-ddTH: dose-dense Adriamycin (Doxorubicin) and Cyclophosphamide, followed by dose-dense Taxol (Paclitaxel) & Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Dang et al. 2008 | 2005 | Phase 2 |
Preceding treatment
Chemotherapy, ddAC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Chemotherapy, ddTH portion (cycles 5 to 8)
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
Targeted therapy, ddTH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 4 mg/kg IV once on day 1, then 2 mg/kg IV once on day 8
- Cycles 6 to 8: 2 mg/kg IV once per day on days 1 & 8
- Cycles 9 to 53: 2 mg/kg IV once on day 1
Supportive therapy, both portions (cycles 1 to 8)
- Pegfilgrastim (Neulasta) 6 mg SC once on day 2, given 24 hours after chemotherapy
14-day cycle for 8 cycles
Subsequent treatment
- Trastuzumab weekly maintenance x 44 weeks (1 year total)
References
- Dang C, Fornier M, Sugarman S, Troso-Sandoval T, Lake D, D'Andrea G, Seidman A, Sklarin N, Dickler M, Currie V, Gilewski T, Moynahan ME, Drullinsky P, Robson M, Wasserheit-Leiblich C, Mills N, Steingart R, Panageas K, Norton L, Hudis C. The safety of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel with trastuzumab in HER-2/neu overexpressed/amplified breast cancer. J Clin Oncol. 2008 Mar 10;26(8):1216-22. link to original article contains dosing details in manuscript PubMed
AC-TH (Docetaxel)
AC-TH: Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxotere (Docetaxel) & Herceptin (Trastuzumab)
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for AC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 5 to 8)
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
21-day cycle for 22 cycles
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for AC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion
- Docetaxel (Taxotere) as follows:
- Cycle 5: 75 mg/m2 IV once on day 1
- Cycles 6 & 7: 100 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
21-day cycle for 22 cycles
Regimen variant #3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for AC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 5 to 7)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
21-day cycle for 22 cycles
Regimen variant #4
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Slamon et al. 2011 (BCIRG 006) | 2001-2004 | Phase 3 (E-RT-esc) | 1. AC-D | Superior OS (secondary endpoint) |
2. TCH | Did not meet primary endpoint of DFS |
Preceding treatment
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 5 to 8)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 6 to 8: 2 mg/kg IV once per day on days 1, 8, 15
- Cycles 9 to 21: 6 mg/kg IV once on day 1
21-day cycle for 21 cycles
References
- BCIRG 006: Slamon D, Eiermann W, Robert N, Pienkowski T, Martín M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J; Breast Cancer International Research Group. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011 Oct 6;365(14):1273-83. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00021255
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains dosing details in supplement link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
AC-THP (Paclitaxel)
AC-THP: Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxol (Paclitaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-2015 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for AC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, THP portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
21-day cycle for 22 cycles
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains dosing details in supplement link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
- KAITLIN: Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. link to original article contains dosing details in supplement link to PMC article PubMed NCT01966471
AC-THP (Docetaxel)
AC-THP: Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxotere (Docetaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-2015 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for AC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, THP portion (cycles 5 to 8)
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
21-day cycle for 22 cycles
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-2015 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for AC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, THP portion
- Docetaxel (Taxotere) as follows:
- Cycle 5: 75 mg/m2 IV once on day 1
- Cycles 6 & 7: 100 mg/m2 IV once on day 1
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
21-day cycle for 22 cycles
Regimen variant #3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-2015 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for AC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, AC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, THP portion (cycles 5 to 7)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
21-day cycle for 22 cycles
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains dosing details in supplement link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
- KAITLIN: Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. link to original article contains dosing details in supplement link to PMC article PubMed NCT01966471
ddAC-TH (Paclitaxel)
ddAC-TH: dose-dense Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxol (Paclitaxel) & Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, ddAC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddAC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, TH portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains dosing details in supplement link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
ddAC-TH (Docetaxel)
ddAC-TH: dose-dense Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxotere (Docetaxel) & Herceptin (Trastuzumab)
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, ddAC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddAC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, TH portion (cycles 5 to 8)
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, ddAC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddAC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, TH portion
- Docetaxel (Taxotere) as follows:
- Cycle 5: 75 mg/m2 IV once on day 1
- Cycles 6 & 7: 100 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
Regimen variant #3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, ddAC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddAC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, TH portion (cycles 5 to 7)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains dosing details in supplement link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
ddAC-THP (Paclitaxel)
ddAC-THP: dose-dense Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxol (Paclitaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-2015 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, ddAC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddAC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, THP portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains dosing details in supplement link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
- KAITLIN: Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. link to original article contains dosing details in supplement link to PMC article PubMed NCT01966471
ddAC-THP (Docetaxel)
ddAC-THP: dose-dense Adriamycin (Doxorubicin) and Cyclophosphamide, followed by Taxotere (Docetaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-2015 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, ddAC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddAC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, THP portion (cycles 5 to 8)
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-2015 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, ddAC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddAC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, THP portion
- Docetaxel (Taxotere) as follows:
- Cycle 5: 75 mg/m2 IV once on day 1
- Cycles 6 & 7: 100 mg/m2 IV once on day 1
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
Regimen variant #3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-2015 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, ddAC portion (cycles 1 to 4)
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddAC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, THP portion (cycles 5 to 7)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains dosing details in supplement link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
- KAITLIN: Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. link to original article contains dosing details in supplement link to PMC article PubMed NCT01966471
EC-TH (Paclitaxel)
EC-TH: Epirubicin and Cyclophosphamide, followed by Taxol (Paclitaxel) & Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for EC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, EC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
21-day cycle for 22 cycles
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains dosing details in supplement link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
EC-TH (Docetaxel)
EC-TH: Epirubicin and Cyclophosphamide, followed by Taxotere (Docetaxel) & Herceptin (Trastuzumab)
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for EC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, EC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 5 to 8)
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
21-day cycle for 22 cycles
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for EC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, EC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion
- Docetaxel (Taxotere) as follows:
- Cycle 5: 75 mg/m2 IV once on day 1
- Cycles 6 & 7: 100 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
21-day cycle for 22 cycles
Regimen variant #3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for EC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, EC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 5 to 7)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
21-day cycle for 22 cycles
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains dosing details in supplement link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
EC-THP (Paclitaxel)
EC-THP: Epirubicin and Cyclophosphamide, followed by Taxol (Paclitaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-2015 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for EC are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m2 of epirubicin per cycle.
Preceding treatment
Chemotherapy, EC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, THP portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
21-day cycle for 22 cycles
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains dosing details in supplement link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
- KAITLIN: Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. link to original article contains dosing details in supplement link to PMC article PubMed NCT01966471
EC-THP (Docetaxel)
EC-THP: Epirubicin and Cyclophosphamide, followed by Taxotere (Docetaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-2015 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for EC are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m2 of epirubicin per cycle.
Preceding treatment
Chemotherapy, EC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, THP portion (cycles 5 to 8)
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
21-day cycle for 22 cycles
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-2015 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for EC are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m2 of epirubicin per cycle.
Preceding treatment
Chemotherapy, EC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, THP portion
- Docetaxel (Taxotere) as follows:
- Cycle 5: 75 mg/m2 IV once on day 1
- Cycles 6 & 7: 100 mg/m2 IV once on day 1
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
21-day cycle for 22 cycles
Regimen variant #3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-2015 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for EC are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m2 of epirubicin per cycle.
Preceding treatment
Chemotherapy, EC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, THP portion (cycles 5 to 7)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
21-day cycle for 22 cycles
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains dosing details in supplement link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
- KAITLIN: Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. link to original article contains dosing details in supplement link to PMC article PubMed NCT01966471
ddEC-TH (Paclitaxel)
ddEC-TH: dose-dense Epirubicin and Cyclophosphamide, followed by Taxol (Paclitaxel) & Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddEC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, ddEC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddEC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, TH portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains dosing details in supplement link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
ddEC-TH (Docetaxel)
ddEC-TH: dose-dense Epirubicin and Cyclophosphamide, followed by Taxotere (Docetaxel) & Herceptin (Trastuzumab)
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddEC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, ddEC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddEC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, TH portion (cycles 5 to 8)
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddEC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, ddEC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddEC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, TH portion
- Docetaxel (Taxotere) as follows:
- Cycle 5: 75 mg/m2 IV once on day 1
- Cycles 6 & 7: 100 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
Regimen variant #3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddEC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, ddEC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddEC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, TH portion (cycles 5 to 7)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains dosing details in supplement link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
ddEC-THP (Paclitaxel)
ddEC-THP: dose-dense Epirubicin and Cyclophosphamide, followed by Taxol (Paclitaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-2015 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddEC are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m2 of epirubicin per cycle.
Preceding treatment
Chemotherapy, ddEC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddEC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, THP portion (cycles 5 to 8)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains dosing details in supplement link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
- KAITLIN: Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. link to original article contains dosing details in supplement link to PMC article PubMed NCT01966471
ddEC-THP (Docetaxel)
ddEC-THP: dose-dense Epirubicin and Cyclophosphamide, followed by Taxotere (Docetaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-2015 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddEC are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m2 of epirubicin per cycle.
Preceding treatment
Chemotherapy, ddEC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddEC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, THP portion (cycles 5 to 8)
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-2015 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddEC are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m2 of epirubicin per cycle.
Preceding treatment
Chemotherapy, ddEC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddEC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, THP portion
- Docetaxel (Taxotere) as follows:
- Cycle 5: 75 mg/m2 IV once on day 1
- Cycles 6 & 7: 100 mg/m2 IV once on day 1
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
Regimen variant #3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-2015 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for ddEC are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m2 of epirubicin per cycle.
Preceding treatment
Chemotherapy, ddEC portion (cycles 1 to 4)
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive therapy, ddEC portion (cycles 1 to 4)
- G-CSF support (drug/dose/schedule not specified)
Chemotherapy, THP portion (cycles 5 to 7)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 8 mg/kg IV once on day 1
- Cycles 6 to 22: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 5: 840 mg IV once on day 1
- Cycles 6 to 22: 420 mg IV once on day 1
14-day cycle for 4 cycles, then 21-day cycle for 18 cycles (1 year)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains dosing details in supplement link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
- KAITLIN: Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. link to original article contains dosing details in supplement link to PMC article PubMed NCT01966471
FAC-TH (Paclitaxel)
FAC-TH: Fluorouracil, Adriamycin (Doxorubicin), Cyclophosphamide, followed by Taxol (Paclitaxel) & Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, FAC portion (cycles 1 to 3)
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 4 to 7)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 4: 8 mg/kg IV once on day 1
- Cycles 5 to 21: 6 mg/kg IV once on day 1
21-day cycle for 21 cycles
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains dosing details in supplement link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
FAC-TH (Docetaxel)
FAC-TH: Fluorouracil, Adriamycin (Doxorubicin), Cyclophosphamide, followed by Taxotere (Docetaxel) & Herceptin (Trastuzumab)
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, FAC portion (cycles 1 to 3)
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 4 to 7)
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 4: 8 mg/kg IV once on day 1
- Cycles 5 to 21: 6 mg/kg IV once on day 1
21-day cycle for 21 cycles
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, FAC portion (cycles 1 to 3)
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion
- Docetaxel (Taxotere) as follows:
- Cycle 4: 75 mg/m2 IV once on day 1
- Cycles 5 & 6: 100 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 4: 8 mg/kg IV once on day 1
- Cycles 5 to 21: 6 mg/kg IV once on day 1
21-day cycle for 21 cycles
Regimen variant #3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, FAC portion (cycles 1 to 3)
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 4 to 6)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 4: 8 mg/kg IV once on day 1
- Cycles 5 to 21: 6 mg/kg IV once on day 1
21-day cycle for 21 cycles
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains dosing details in supplement link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
FAC-THP (Paclitaxel)
FAC-THP: Fluorouracil, Adriamycin (Doxorubicin), Cyclophosphamide, followed by Taxol (Paclitaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, FAC portion (cycles 1 to 3)
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, THP portion (cycles 4 to 7)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 4: 8 mg/kg IV once on day 1
- Cycles 5 to 21: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 4: 840 mg IV once on day 1
- Cycles 5 to 21: 420 mg IV once on day 1
21-day cycle for 21 cycles
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains dosing details in supplement link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
FAC-THP (Docetaxel)
FAC-THP: Fluorouracil, Adriamycin (Doxorubicin), Cyclophosphamide, followed by Taxotere (Docetaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, FAC portion (cycles 1 to 3)
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, THP portion (cycles 4 to 7)
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 4: 8 mg/kg IV once on day 1
- Cycles 5 to 21: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 4: 840 mg IV once on day 1
- Cycles 5 to 21: 420 mg IV once on day 1
21-day cycle for 21 cycles
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, FAC portion (cycles 1 to 3)
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, THP portion
- Docetaxel (Taxotere) as follows:
- Cycle 4: 75 mg/m2 IV once on day 1
- Cycles 5 & 6: 100 mg/m2 IV once on day 1
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 4: 8 mg/kg IV once on day 1
- Cycles 5 to 21: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 4: 840 mg IV once on day 1
- Cycles 5 to 21: 420 mg IV once on day 1
21-day cycle for 21 cycles
Regimen variant #3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FAC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, FAC portion (cycles 1 to 3)
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, THP portion (cycles 4 to 6)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 4: 8 mg/kg IV once on day 1
- Cycles 5 to 21: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 4: 840 mg IV once on day 1
- Cycles 5 to 21: 420 mg IV once on day 1
21-day cycle for 21 cycles
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains dosing details in supplement link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
FEC-TH (Paclitaxel)
FEC-TH: Fluorouracil, Epirubicin, Cyclophosphamide, followed by Taxol (Paclitaxel) & Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FEC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, FEC portion (cycles 1 to 3)
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 4 to 7)
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 4: 8 mg/kg IV once on day 1
- Cycles 5 to 21: 6 mg/kg IV once on day 1
21-day cycle for 21 cycles
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains dosing details in supplement link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
FEC-TH (Docetaxel)
FEC-TH: Fluorouracil, Epirubicin, Cyclophosphamide, followed by Taxotere (Docetaxel) & Herceptin (Trastuzumab)
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FEC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, FEC portion (cycles 1 to 3)
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 4 to 7)
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 4: 8 mg/kg IV once on day 1
- Cycles 5 to 21: 6 mg/kg IV once on day 1
21-day cycle for 21 cycles
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FEC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, FEC portion (cycles 1 to 3)
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion
- Docetaxel (Taxotere) as follows:
- Cycle 4: 75 mg/m2 IV once on day 1
- Cycles 5 & 6: 100 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 4: 8 mg/kg IV once on day 1
- Cycles 5 to 21: 6 mg/kg IV once on day 1
21-day cycle for 21 cycles
Regimen variant #3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (C) | 1a. AC-THP (Paclitaxel) 1b. AC-THP (Docetaxel) 1c. ddAC-THP (Paclitaxel) 1c. ddAC-THP (Docetaxel) 1e. EC-THP (Paclitaxel) 1f. EC-THP (Docetaxel) 1g. ddEC-THP (Paclitaxel) 1h. ddEC-THP (Docetaxel) 1i. FAC-THP (Paclitaxel) 1j. FAC-THP (Docetaxel) 1k. FEC-THP (Paclitaxel) 1l. FEC-THP (Docetaxel) 1m. TCHP (Docetaxel) |
Inferior IDFS1 |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FEC are given in the protocol, replicated here.
Preceding treatment
Chemotherapy, FEC portion (cycles 1 to 3)
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Chemotherapy, TH portion (cycles 4 to 6)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 4: 8 mg/kg IV once on day 1
- Cycles 5 to 21: 6 mg/kg IV once on day 1
21-day cycle for 21 cycles
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains dosing details in supplement link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
ddFEC-ddTH (Docetaxel)
ddFEC-ddTH (Docetaxel): dose-dense Fluorouracil, Epirubicin, Cyclophosphamide, followed by ddTH: dose-dense Taxotere (Docetaxel) & Herceptin (Trastuzumab)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mavroudis et al. 2015 (HORG CT/04.23) | 2004-2012 | Phase 3 (C) | ddFEC-ddTH; 6-months total of trastuzumab | Inconclusive whether non-inferior DFS36 |
Preceding treatment
Chemotherapy, ddFEC portion (cycles 1 to 4)
- Fluorouracil (5-FU) 700 mg/m2 IV over 5 to 15 minutes once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV over 5 to 15 minutes once on day 1
- Cyclophosphamide (Cytoxan) 700 mg/m2 IV over 30 to 60 minutes once on day 1
Chemotherapy, ddTH portion (cycles 5 to 8)
- Docetaxel (Taxotere) 75 mg/m2 IV over 60 minutes once on day 1
Targeted therapy, ddTH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 5: 6 mg/kg IV once on day 1
- Cycles 6 to 8: 4 mg/kg IV once on day 1
- Cycles 9 to 24: 6 mg/kg IV once on day 1
Supportive therapy, both portions (cycles 1 to 8)
- Filgrastim (Neupogen) 5 mcg/kg (rounded to 300 or 480 mcg) SC once per day on days 3 to 10
14-day cycle for 8 cycles
Subsequent treatment
- Trastuzumab q3wk maintenance x 15 cycles
References
- HORG CT/04.23: Mavroudis D, Saloustros E, Malamos N, Kakolyris S, Boukovinas I, Papakotoulas P, Kentepozidis N, Ziras N, Georgoulias V; Hellenic Oncology Research Group. Six versus 12 months of adjuvant trastuzumab in combination with dose-dense chemotherapy for women with HER2-positive breast cancer: a multicenter randomized study by the Hellenic Oncology Research Group (HORG). Ann Oncol. 2015 Jul;26(7):1333-40. Epub 2015 May 1. link to original article contains dosing details in manuscript PubMed NCT00615602
FEC-THP (Paclitaxel)
FEC-THP: Fluorouracil, Epirubicin, Cyclophosphamide, followed by Taxol (Paclitaxel), Herceptin (Trastuzumab), Pertuzumab
Protocol
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-2015 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FEC dosing and number of cycles are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m2 of epirubicin per cycle.
Preceding treatment
Chemotherapy, FEC portion
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
21-day cycle for 3 to 4 cycles
Chemotherapy, THP portion
- Paclitaxel (Taxol) as follows:
- Cycles 1 to 4: 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 18: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycles 2 to 18: 420 mg IV once on day 1
21-day cycle for 18 cycles (1 year)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains dosing details in supplement link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
- KAITLIN: Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. link to original article contains dosing details in supplement link to PMC article PubMed NCT01966471
FEC-THP (Docetaxel)
FEC-THP: Fluorouracil, Epirubicin, Cyclophosphamide, followed by Taxotere (Docetaxel), Herceptin (Trastuzumab), Pertuzumab
Protocol variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-2015 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FEC dosing and number of cycles are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m2 of epirubicin per cycle.
Preceding treatment
Chemotherapy, FEC portion
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
21-day cycle for 3 to 4 cycles
Chemotherapy, THP portion
- Docetaxel (Taxotere) as follows:
- Cycles 1 to 4: 75 mg/m2 IV once on day 1
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 18: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycles 2 to 18: 420 mg IV once on day 1
21-day cycle for 18 cycles (1 year)
Protocol variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-2015 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FEC dosing and number of cycles are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m2 of epirubicin per cycle.
Preceding treatment
Chemotherapy, FEC portion
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
21-day cycle for 3 to 4 cycles
Chemotherapy, THP portion
- Docetaxel (Taxotere) as follows:
- Cycle 1: 75 mg/m2 IV once on day 1
- Cycles 2 & 3: 100 mg/m2 IV once on day 1
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 18: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycles 2 to 18: 420 mg IV once on day 1
21-day cycle for 18 cycles (1 year)
Protocol variant #3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | 2011-2013 | Phase 3 (E-esc) | 1a. AC-TH (Paclitaxel) 1b. AC-TH (Docetaxel) 1c. ddAC-TH (Paclitaxel) 1d. ddAC-TH (Docetaxel) 1e. EC-TH (Paclitaxel) 1f. EC-TH (Docetaxel) 1g. ddEC-TH (Paclitaxel) 1h. ddEC-TH (Docetaxel) 1i. FAC-TH (Paclitaxel) 1j. FAC-TH (Docetaxel) 1k. FEC-TH (Paclitaxel) 1l. FEC-TH (Docetaxel) 1m. TCH (Taxotere) |
Superior IDFS1 (primary endpoint) IDFS72: 91% vs 88% (HR 0.76, 95% CI 0.64-0.91) |
Krop et al. 2021 (KAITLIN) | 2014-2015 | Phase 3 (C) | 1a. AC-KP 1b. ddAC-KP 1c. EC-KP 1d. ddEC-KP 1e. FEC-KP |
Did not meet primary endpoint of IDFS |
1Reported efficacy for APHINITY is based on the 2021 update.
Note that ranges for FEC dosing and number of cycles are given in the protocol, replicated here; KAITLIN only allowed up to 100 mg/m2 of epirubicin per cycle.
Preceding treatment
Chemotherapy, FEC portion
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
21-day cycle for 3 to 4 cycles
Chemotherapy, THP portion
- Docetaxel (Taxotere) as follows:
- Cycles 1 to 3: 100 mg/m2 IV once on day 1
Targeted therapy, THP portion
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 18: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycles 2 to 18: 420 mg IV once on day 1
21-day cycle for 18 cycles (1 year)
References
- APHINITY: von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains dosing details in supplement link to PMC article PubMed NCT01358877
- Update: Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C; APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. J Clin Oncol. 2021 May 1;39(13):1448-1457. Epub 2021 Feb 4. link to original article PubMed
- KAITLIN: Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448. Epub 2021 Dec 10. link to original article contains dosing details in supplement link to PMC article PubMed NCT01966471
TH-FEC (Docetaxel)
TH-FEC: Taxotere (Docetaxel) & Herceptin (Trastuzumab), followed by Fluorouracil, Epirubicin, Cyclophosphamide
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Joensuu et al. 2006 (FinHer) | 2000-2003 | Phase 3 (E-esc) | 1. D-FEC 2. V-FEC |
Superior RFS (primary endpoint) Median RFS: NYR vs NYR (HR 0.42, 95% CI 0.21-0.83) |
3. VH-FEC | Not reported |
Preceding treatment
Chemotherapy, TH portion (cycles 1 to 3)
- Docetaxel (Taxotere) 100 mg/m2 IV over 60 minutes once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 2 & 3: 2 mg/kg IV once per day on days 1, 8, 15
Chemotherapy, FEC portion (cycles 4 to 6)
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 6 cycles
Regimen variant #2, 600/75/600 x 3
Study | Dates of enrollment | Evidence |
---|---|---|
Joensuu et al. 2018 (SOLD) | 2008-2014 | Non-randomized part of phase 3 RCT |
Preceding treatment
Chemotherapy, TH portion (cycles 1 to 3)
- Docetaxel (Taxotere) 80 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 & 3: 6 mg/kg IV once on day 1
Chemotherapy, FEC portion (cycles 4 to 6)
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 6 cycles
Subsequent treatment
- Trastuzumab maintenance for a total of 1 year versus no further treatment
Regimen variant #3
Study | Dates of enrollment | Evidence |
---|---|---|
Joensuu et al. 2018 (SOLD) | 2008-2014 | Non-randomized part of phase 3 RCT |
Preceding treatment
Chemotherapy, TH portion (cycles 1 to 3)
- Docetaxel (Taxotere) 80 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 2 & 3: 2 mg/kg IV once per day on days 1, 8, 15
Chemotherapy, FEC portion (cycles 4 to 6)
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 6 cycles
Subsequent treatment
- Trastuzumab maintenance for a total of 1 year versus no further treatment
Regimen variant #4
Study | Dates of enrollment | Evidence |
---|---|---|
Joensuu et al. 2018 (SOLD) | 2008-2014 | Non-randomized part of phase 3 RCT |
Preceding treatment
Chemotherapy, TH portion (cycles 1 to 3)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 & 3: 6 mg/kg IV once on day 1
Chemotherapy, FEC portion (cycles 4 to 6)
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 6 cycles
Subsequent treatment
- Trastuzumab maintenance for a total of 1 year versus no further treatment
Regimen variant #5
Study | Dates of enrollment | Evidence |
---|---|---|
Joensuu et al. 2018 (SOLD) | 2008-2014 | Non-randomized part of phase 3 RCT |
Preceding treatment
Chemotherapy, TH portion (cycles 1 to 3)
- Docetaxel (Taxotere) 100 mg/m2 IV over 60 minutes once on day 1
Targeted therapy, TH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 2 & 3: 2 mg/kg IV once per day on days 1, 8, 15
Chemotherapy, FEC portion (cycles 4 to 6)
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 6 cycles
Subsequent treatment
- Trastuzumab maintenance for a total of 1 year versus no further treatment
References
- FinHer: Joensuu H, Kellokumpu-Lehtinen PL, Bono P, Alanko T, Kataja V, Asola R, Utriainen T, Kokko R, Hemminki A, Tarkkanen M, Turpeenniemi-Hujanen T, Jyrkkiö S, Flander M, Helle L, Ingalsuo S, Johansson K, Jääskeläinen AS, Pajunen M, Rauhala M, Kaleva-Kerola J, Salminen T, Leinonen M, Elomaa I, Isola J; FinHer Study Investigators. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006 Feb 23;354(8):809-20. link to original article contains dosing details in manuscript PubMed ISRCTN76560285
- Update: Joensuu H, Bono P, Kataja V, Alanko T, Kokko R, Asola R, Utriainen T, Turpeenniemi-Hujanen T, Jyrkkiö S, Möykkynen K, Helle L, Ingalsuo S, Pajunen M, Huusko M, Salminen T, Auvinen P, Leinonen H, Leinonen M, Isola J, Kellokumpu-Lehtinen PL. Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer trial. J Clin Oncol. 2009 Dec 1;27(34):5685-92. link to original article PubMed
- SOLD: Joensuu H, Fraser J, Wildiers H, Huovinen R, Auvinen P, Utriainen M, Nyandoto P, Villman KK, Halonen P, Granstam-Björneklett H, Lundgren L, Sailas L, Turpeenniemi-Hujanen T, Tanner M, Yachnin J, Ritchie D, Johansson O, Huttunen T, Neven P, Canney P, Harvey VJ, Kellokumpu-Lehtinen PL, Lindman H. Effect of adjuvant trastuzumab for a duration of 9 weeks vs 1 year with concomitant chemotherapy for early human epidermal growth factor receptor 2-positive breast cancer: the SOLD randomized clinical trial. JAMA Oncol. 2018 Sep 1;4(9):1199-1206. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00593697
TH-FEC (Docetaxel, SC Trastuzumab)
TH-FEC: Taxotere (Docetaxel) & Herceptin Hylecta (Trastuzumab and hyaluronidase), followed by Fluorouracil, Epirubicin, Cyclophosphamide
Regimen variant #1, 80 x 3, q3wk trastuzumab
Study | Dates of enrollment | Evidence |
---|---|---|
Joensuu et al. 2018 (SOLD) | 2008-2014 | Non-randomized part of phase 3 RCT |
Preceding treatment
Chemotherapy, TH portion (cycles 1 to 3)
- Docetaxel (Taxotere) 80 mg/m2 IV once on day 1
Targeted therapy, TH portion (cycles 1 to 3)
- Trastuzumab and hyaluronidase (Herceptin Hylecta) 600 mg/10,000 units SC once on day 1
Chemotherapy, FEC portion (cycles 4 to 6)
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 6 cycles
Subsequent treatment
- trastuzumab maintenance for a total of 1 year versus no further treatment
Regimen variant #2, 100 x 3, q3wk trastuzumab
Study | Dates of enrollment | Evidence |
---|---|---|
Joensuu et al. 2018 (SOLD) | 2008-2014 | Non-randomized part of phase 3 RCT |
Preceding treatment
Chemotherapy, TH portion (cycles 1 to 3)
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy, TH portion (cycles 1 to 3)
- Trastuzumab and hyaluronidase (Herceptin Hylecta) 600 mg/10,000 units SC once on day 1
Chemotherapy, FEC portion (cycles 4 to 6)
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 6 cycles
Subsequent treatment
- trastuzumab maintenance for a total of 1 year versus no further treatment
References
- SOLD: Joensuu H, Fraser J, Wildiers H, Huovinen R, Auvinen P, Utriainen M, Nyandoto P, Villman KK, Halonen P, Granstam-Björneklett H, Lundgren L, Sailas L, Turpeenniemi-Hujanen T, Tanner M, Yachnin J, Ritchie D, Johansson O, Huttunen T, Neven P, Canney P, Harvey VJ, Kellokumpu-Lehtinen PL, Lindman H. Effect of adjuvant trastuzumab for a duration of 9 weeks vs 1 year with concomitant chemotherapy for early human epidermal growth factor receptor 2-positive breast cancer: the SOLD randomized clinical trial. JAMA Oncol. 2018 Sep 1;4(9):1199-1206. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00593697
VH-FEC
VH-FEC: Vinorelbine & Herceptin (Trastuzumab), followed by Fluorouracil, Epirubicin, Cyclophosphamide
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Joensuu et al. 2006 (FinHer) | 2000-2003 | Phase 3 (E-esc) | 1. D-FEC 2. V-FEC |
Superior RFS (primary endpoint) Median RFS: NYR vs NYR (HR 0.42, 95% CI 0.21-0.83) |
3. TH-FEC | Not reported |
Preceding treatment
Chemotherapy, VH portion (cycles 1 to 3)
- Vinorelbine (Navelbine) 24 mg/m2 IV over 5 to 10 minutes once per day on days 1, 8, 15
Targeted therapy, VH portion
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 2 & 3: 2 mg/kg IV once per day on days 1, 8, 15
Chemotherapy, FEC portion (cycles 4 to 6)
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 6 cycles
References
- FinHer: Joensuu H, Kellokumpu-Lehtinen PL, Bono P, Alanko T, Kataja V, Asola R, Utriainen T, Kokko R, Hemminki A, Tarkkanen M, Turpeenniemi-Hujanen T, Jyrkkiö S, Flander M, Helle L, Ingalsuo S, Johansson K, Jääskeläinen AS, Pajunen M, Rauhala M, Kaleva-Kerola J, Salminen T, Leinonen M, Elomaa I, Isola J; FinHer Study Investigators. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006 Feb 23;354(8):809-20. link to original article PubMed ISRCTN76560285
- Update: Joensuu H, Bono P, Kataja V, Alanko T, Kokko R, Asola R, Utriainen T, Turpeenniemi-Hujanen T, Jyrkkiö S, Möykkynen K, Helle L, Ingalsuo S, Pajunen M, Huusko M, Salminen T, Auvinen P, Leinonen H, Leinonen M, Isola J, Kellokumpu-Lehtinen PL. Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer trial. J Clin Oncol. 2009 Dec 1;27(34):5685-92. link to original article PubMed
Adjuvant therapy
Docetaxel & Trastuzumab (TH)
TH: Taxotere (Docetaxel) & Herceptin (Trastuzumab)
Regimen variant #1, 75 x 4, q3wk trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sawaki et al. 2020 (RESPECT) | 2009-2014 | Randomized (C) | Trastuzumab x 12 mo | Inconclusive whether non-inferior DFS |
Preceding treatment
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 4: 6 mg/kg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- Trastuzumab maintenance (q3wk) for a total of 1 year
Regimen variant #2, 75 x 4, weekly trastuzumab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Piccart-Gebhart et al. 2015 (ALTTO) | 2007-2011 | Phase 3 (C) | 1a. TH (Docetaxel), then Lapatinib 1b. THL (Taxotere) 1c. TL (Docetaxel) |
Did not meet primary endpoint of DFS |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 2 to 4: 2 mg/kg IV once per day on days 1, 8, 15
21-day cycle for 4 cycles
Subsequent treatment
- Trastuzumab maintenance (q3wk) for a total of 1 year
References
- ALTTO: Piccart-Gebhart M, Holmes E, Baselga J, de Azambuja E, Dueck AC, Viale G, Zujewski JA, Goldhirsch A, Armour A, Pritchard KI, McCullough AE, Dolci S, McFadden E, Holmes AP, Tonghua L, Eidtmann H, Dinh P, Di Cosimo S, Harbeck N, Tjulandin S, Im YH, Huang CS, Diéras V, Hillman DW, Wolff AC, Jackisch C, Lang I, Untch M, Smith I, Boyle F, Xu B, Gomez H, Suter T, Gelber RD, Perez EA. Adjuvant lapatinib and trastuzumab for early human epidermal growth factor receptor 2-positive breast cancer: results from the randomized phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial. J Clin Oncol. 2016 Apr 1;34(10):1034-42. Epub 2015 Nov 23. link to original article link to protocol contains dosing details in supplement link to PMC article PubMed NCT00490139
- Update: Moreno-Aspitia A, Holmes EM, Jackisch C, de Azambuja E, Boyle F, Hillman DW, Korde L, Fumagalli D, Izquierdo MA, McCullough AE, Wolff AC, Pritchard KI, Untch M, Guillaume S, Ewer MS, Shao Z, Sim SH, Aziz Z, Demetriou G, Mehta AO, Andersson M, Toi M, Lang I, Xu B, Smith IE, Barrios CH, Baselga J, Gelber RD, Piccart-Gebhart M; ALTTO Steering Committee and Investigators. Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D). Eur J Cancer. 2021 May;148:287-296. Epub 2021 Mar 23. link to original article link to PMC article PubMed
- RESPECT: Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. link to original article contains dosing details in manuscript PubMed NCT01104935
FEC
FEC: Fluorouracil, Epirubicin, Cyclophosphamide
CEF: Cyclophosphamide, Epirubicin, Fluorouracil
Regimen variant #1, 500/100/500 x 3 ("FEC 100")
Study | Dates of enrollment | Evidence |
---|---|---|
Baselga et al. 2012 (NeoALTTO) | 2008-2010 | Non-randomized part of phase 3 RCT |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
- Lapatinib or Lapatinib & Trastuzumab or Trastuzumab, according to initial randomization
References
- NeoALTTO: Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00553358
- Update: de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. Epub 2014 Aug 14. link to original article PubMed
- Update: Huober J, Holmes E, Baselga J, de Azambuja E, Untch M, Fumagalli D, Sarp S, Lang I, Smith I, Boyle F, Xu B, Lecocq C, Wildiers H, Jouannaud C, Hackman J, Dasappa L, Ciruelos E, Toral Pena JC, Adamchuk H, Hickish T, de la Pena L, Jackisch C, Gelber RD, Piccart-Gebhart M, Di Cosimo S. Survival outcomes of the NeoALTTO study (BIG 1-06): updated results of a randomised multicenter phase III neoadjuvant clinical trial in patients with HER2-positive primary breast cancer. Eur J Cancer. 2019 Sep;118:169-177. Epub 2019 Aug 1. link to original article PubMed
- RESPECT: Sawaki M, Taira N, Uemura Y, Saito T, Baba S, Kobayashi K, Kawashima H, Tsuneizumi M, Sagawa N, Bando H, Takahashi M, Yamaguchi M, Takashima T, Nakayama T, Kashiwaba M, Mizuno T, Yamamoto Y, Iwata H, Kawahara T, Ohashi Y, Mukai H; RESPECT study group. Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients. J Clin Oncol. 2020 Nov 10;38(32):3743-3752. Epub 2020 Sep 16. link to original article contains dosing details in manuscript PubMed NCT01104935
FEC & H
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Gianni et al. 2011 (NeoSphere) | 2007-2009 | Non-randomized part of phase 2 RCT |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Neoadjuvant Docetaxel & Pertuzumab versus THP (Docetaxel) versus pertuzumab & trastuzumab versus TH (Docetaxel), then surgery
Chemotherapy
- Fluorouracil (5-FU) as follows:
- Cycles 1 to 3: 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) as follows:
- Cycles 1 to 3: 90 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) as follows:
- Cycles 1 to 3: 600 mg/m2 IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) 6 mg/kg IV once on day 1
21-day cycle for 18 cycles
Subsequent treatment
- NeoSphere, ER-positive patients: Radiotherapy and/or hormone therapy "per local guidelines"
References
- NeoSphere: Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, Lluch A, Staroslawska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi G, Szado T, Ratnayake J, Ross G, Valagussa P. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012 Jan;13(1):25-32. Epub 2011 Dec 6. link to original article contains dosing details in manuscript PubMed NCT00545688
- Update: Gianni L, Pienkowski T, Im YH, Tseng LM, Liu MC, Lluch A, Starosławska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi GV, Magazzù D, McNally V, Douthwaite H, Ross G, Valagussa P. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 2016 Jun;17(6):791-800. Epub 2016 May 11. link to original article PubMed
Lapatinib & Trastuzumab
L+T: Lapatinib & Trastuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Piccart-Gebhart et al. 2015 (ALTTO) | 2007-2011 | Phase 3 (E-esc) | 1a. Lapatinib | Did not meet primary endpoint of DFS |
1b. Trastuzumab | Might have superior DFS1 (HR 0.86, 95% CI 0.74-1.00) | |||
Baselga et al. 2012 (NeoALTTO) | 2008-2010 | Phase 3 (E-esc) | See link | See link |
1Reported efficacy is based on the 2021 update.
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Targeted therapy
- Lapatinib (Tykerb) 1000 mg PO once per day
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV over 90 minutes once on day 1
- Cycles 2 to 12: 6 mg/kg IV over 30 minutes once on day 1
21-day cycle for 12 cycles (34-week course)
References
- NeoALTTO: Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00553358
- Update: de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. Epub 2014 Aug 14. link to original article PubMed
- Update: Huober J, Holmes E, Baselga J, de Azambuja E, Untch M, Fumagalli D, Sarp S, Lang I, Smith I, Boyle F, Xu B, Lecocq C, Wildiers H, Jouannaud C, Hackman J, Dasappa L, Ciruelos E, Toral Pena JC, Adamchuk H, Hickish T, de la Pena L, Jackisch C, Gelber RD, Piccart-Gebhart M, Di Cosimo S. Survival outcomes of the NeoALTTO study (BIG 1-06): updated results of a randomised multicenter phase III neoadjuvant clinical trial in patients with HER2-positive primary breast cancer. Eur J Cancer. 2019 Sep;118:169-177. Epub 2019 Aug 1. link to original article PubMed
- ALTTO: Piccart-Gebhart M, Holmes E, Baselga J, de Azambuja E, Dueck AC, Viale G, Zujewski JA, Goldhirsch A, Armour A, Pritchard KI, McCullough AE, Dolci S, McFadden E, Holmes AP, Tonghua L, Eidtmann H, Dinh P, Di Cosimo S, Harbeck N, Tjulandin S, Im YH, Huang CS, Diéras V, Hillman DW, Wolff AC, Jackisch C, Lang I, Untch M, Smith I, Boyle F, Xu B, Gomez H, Suter T, Gelber RD, Perez EA. Adjuvant lapatinib and trastuzumab for early human epidermal growth factor receptor 2-positive breast cancer: results from the randomized phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial. J Clin Oncol. 2016 Apr 1;34(10):1034-42. Epub 2015 Nov 23. link to original article link to protocol contains dosing details in supplement link to PMC article PubMed NCT00490139
- Update: Moreno-Aspitia A, Holmes EM, Jackisch C, de Azambuja E, Boyle F, Hillman DW, Korde L, Fumagalli D, Izquierdo MA, McCullough AE, Wolff AC, Pritchard KI, Untch M, Guillaume S, Ewer MS, Shao Z, Sim SH, Aziz Z, Demetriou G, Mehta AO, Andersson M, Toi M, Lang I, Xu B, Smith IE, Barrios CH, Baselga J, Gelber RD, Piccart-Gebhart M; ALTTO Steering Committee and Investigators. Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D). Eur J Cancer. 2021 May;148:287-296. Epub 2021 Mar 23. link to original article link to PMC article PubMed
Neratinib monotherapy
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Chan et al. 2016 (ExteNET)
Pertuzumab and Trastuzumab hyaluronidase monotherapyRegimen
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. Preceding treatment
Targeted therapy
21-day cycle for 14 cycles (42 weeks) References
TCH (Docetaxel, Carboplatin)TCH: Taxotere (Docetaxel), Carboplatin, Herceptin (Trastuzumab) Regimen variant #1, capped carboplatin
1Reported efficacy is based on the 2021 update. Preceding treatmentChemotherapy
Targeted therapy
21-day cycle for up to 18 cycles (1 year) Regimen variant #2, no cap
Preceding treatmentChemotherapy
Targeted therapy
Supportive therapy
21-day cycle for 18 cycles (1 year) References
TCH (Docetaxel, Cyclophosphamide)TCH: Taxotere, Cyclophosphamide, Herceptin Regimen
Preceding treatment
Chemotherapy
Targeted therapy
Supportive therapy
21-day cycle for 18 cycles References
TCHP (Docetaxel)TCHP: Taxotere (Docetaxel), Carboplatin, Herceptin (Trastuzumab), Pertuzumab Regimen
1Reported efficacy is based on the 2021 update. Preceding treatmentChemotherapy
Targeted therapy
21-day cycle for up to 18 cycles (1 year) References
Trastuzumab monotherapyRegimen variant #1, 6 mo course
Preceding treatment
Targeted therapy
21-day cycle for 9 cycles (6 months) Regimen variant #2, 30-week course, q3wk
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. Preceding treatment
Targeted therapy
21-day cycle for 10 cycles (30-week course) Regimen variant #3, 34-week course, q3wk
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. Targeted therapy
21-day cycle for 12 cycles (34-week course) Regimen variant #4, 42-week course, q3wk
Note: the loading dose in cycle 1 was only used if it had been more than 6 weeks since any preceding dose of trastuzumab. Preceding treatment
Targeted therapy
21-day cycle for 14 cycles Regimen variant #5, 1-year total course, q3wk
1Reported efficacy for HERA is based on the 2017 update. Preceding treatment
Targeted therapy
21-day cycle for 18 cycles (1 year) Regimen variant #6, 2-year course
Preceding treatment
Targeted therapy
21-day cycle for 35 cycles (2 years) References
Trastuzumab and hyaluronidase monotherapyRegimen variant #1, 6 mos
Preceding treatment
Targeted therapy
21-day cycle for 9 cycles (6 months) Regimen variant #2, 12 mos
Preceding treatment
Targeted therapy
21-day cycle for 18 cycles (1 year) References
Trastuzumab emtansine monotherapyT-DM1: Trastuzumab-DM1 (Trastuzumab emtansine) Example ordersRegimen
Preceding treatment
Antibody-drug conjugate therapy
21-day cycle for 14 cycles References
Metastatic or unresectable disease, first-lineNote: some patients in these trials were pre-treated with non-HER2-targeted therapies. ACHACH: Adriamycin (Doxorubicin), Cyclophosphamide, Herceptin (Trastuzumab) Regimen
Note: This is not commonly used; here for reference purposes only. Prior treatment criteria
ChemotherapyTargeted therapyReferences
Capecitabine, Bevacizumab, TrastuzumabRegimen
Chemotherapy
Targeted therapy
21-day cycles References
Capecitabine & LapatinibRegimen
Chemotherapy
Targeted therapy
21-day cycles References
Capecitabine & Trastuzumab (XH)XH: Xeloda (Capecitabine) & Herceptin Regimen
Chemotherapy
Targeted therapy
21-day cycles References
Carboplatin & Paclitaxel (CP) & TrastuzumabTPC: Trastuzumab, Paclitaxel, Carboplatin
Regimen variant #1, weekly
Targeted therapy
Chemotherapy
28-day cycle for 6 cycles Subsequent treatmentRegimen variant #2, weekly T, q3wk PC
Targeted therapy
Chemotherapy
21-day cycle for at least 6 cycles Subsequent treatmentRegimen variant #3, q3wk
Targeted therapy
Chemotherapy
21-day cycle for 8 cycles Subsequent treatmentReferences
ECHECH: Epirubicin, Cyclophosphamide, Herceptin (Trastuzumab) Regimen
Note: This is not commonly used; here for reference purposes only. Prior treatment criteria
ChemotherapyTargeted therapyReferences
nab-Paclitaxel & TrastuzumabRegimen
Chemotherapy
Targeted therapy
28-day cycles References
Pertuzumab & T-DM1Pertuzumab & T-DM1: Pertuzumab & Trastuzumab-DM1 (Trastuzumab emtansine) Regimen
Targeted therapy
Antibody-drug conjugate therapy
21-day cycles References
TCH (Docetaxel, Carboplatin)TCH: Taxotere (Docetaxel), Carboplatin, Herceptin (Trastuzumab) Regimen
Chemotherapy
Targeted therapy
21-day cycle for 8 cycles Subsequent treatment
References
Docetaxel & Trastuzumab (TH)TH: Taxotere (Docetaxel) & Herceptin (Trastuzumab)
Regimen variant #1, 35 mg/m2 docetaxel, 3 out of 4 weeks
Note: Esteva et al. 2002 described the day before the start of a cycle as "day 0," which is not the typical convention, so day -1 is being used instead. Chemotherapy
Targeted therapy
Supportive therapy
28-day cycles Regimen variant #2, 60 mg/m2 q3wk docetaxel, weekly trastuzumab
Chemotherapy
Targeted therapy
21-day cycles Regimen variant #3, 75 mg/m2 q3wk docetaxel, q3wk trastuzumab
1Reported efficacy for CLEOPATRA is based on the 2020 update. Chemotherapy
Targeted therapy
21-day cycle for at least 6 cycles Subsequent treatment
Regimen variant #4, 100 mg/m2 q3wk docetaxel, weekly trastuzumab
Chemotherapy
Targeted therapy
Supportive therapy
21-day cycle for 6 cycles (M77001; see note) or 8 cycles (BCIRG 007) Subsequent treatment
Regimen variant #5, 100 mg/m2 q3wk docetaxel, q3wk trastuzumab
Note: In HERNATA, the day of docetaxel and trastuzumab were reversed in cycle 1. Dose of docetaxel in TDM4450g and MARIANNE was per investigator's discretion. Chemotherapy
Targeted therapy
21-day cycles References
Paclitaxel & Trastuzumab (TH)TH: Taxol (Paclitaxel), Herceptin (Trastuzumab)
Regimen variant #1, weekly paclitaxel (80 mg/m2)
Chemotherapy
Targeted therapy
28-day cycles Regimen variant #2, weekly paclitaxel (90 mg/m2)
Chemotherapy
Targeted therapy
28-day cycles Regimen variant #3, paclitaxel 3 weeks out of 4, 6 cycles
Chemotherapy
Targeted therapy
28-day cycle for 6 cycles Subsequent treatment
Regimen variant #4, paclitaxel 3 weeks out of 4, indefinite
Chemotherapy
Targeted therapy
28-day cycles Regimen variant #5, q3wk paclitaxel
Prior treatment criteria
Chemotherapy
Targeted therapy
21-day cycle for at least 6 cycles References
THP (Docetaxel)THP: Taxotere (Docetaxel), Herceptin (Trastuzumab), Pertuzumab Regimen
1Reported efficacy for CLEOPATRA is based on the 2020 update. Chemotherapy
Targeted therapy
21-day cycle for at least 6 cycles Subsequent treatment
References
Lapatinib & Paclitaxel (TL)TL: Taxol (Paclitaxel) & Lapatinib Regimen
Chemotherapy
Targeted therapy
28-day cycles References
Trastuzumab monotherapyRegimen variant #1
Targeted therapy
7-day cycles Regimen variant #2, flat dose
Note: this variant is of historical interest, only. Targeted therapy
7-day cycle for 11 cycles References
Trastuzumab emtansine monotherapyT-DM1: Trastuzumab-DM1 (Trastuzumab emtansine) Example ordersRegimen
Antibody-drug conjugate therapy
21-day cycles References
Vinorelbine & Trastuzumab (VH)VH: Vinorelbine & Herceptin (Trastuzumab) Regimen variant #1, vinorelbine 25 mg/m2
Chemotherapy
Targeted therapy
28-day cycles Regimen variant #2, vinorelbine 30 mg/m2, 2 out of 3 weeks
Chemotherapy
Targeted therapy
21-day cycles Regimen variant #3, vinorelbine 35 mg/m2, 2 out of 3 weeks
Chemotherapy
Targeted therapy
21-day cycles References
Metastatic or unresectable disease, subsequent linesCapecitabine & LapatinibRegimen
1Reported efficacy for PFS for EGF100151 is based on the 2008 update. Chemotherapy
Targeted therapy
21-day cycles References
Capecitabine & MargetuximabRegimen
1Reported efficacy is based on the 2022 update. Chemotherapy
Targeted therapy
21-day cycles References
Capecitabine & NeratinibRegimen
Chemotherapy
Targeted therapy
21-day cycles References
Capecitabine & PyrotinibRegimen
Chemotherapy
Targeted therapy
21-day cycles References
Capecitabine & Trastuzumab (XH)XH: Xeloda (Capecitabine) & Herceptin Regimen variant #1, 2000/6, with loading dose
Chemotherapy
Targeted therapy
21-day cycles Regimen variant #2, 2500/6, with loading dose
Note: the only difference between this and the next variant is the use of a loading dose of trastuzumab. The primary endpoint of CEREBEL was incidence of CNS as site of first relapse; this was very low in both arms, with no statistically significant difference. Prior treatment criteria
Chemotherapy
Targeted therapy
21-day cycles Regimen variant #3, 2500/6, no loading dose
Note: This is a continuation of trastuzumab so there is no loading dose. Chemotherapy
Targeted therapy
21-day cycles References
Capecitabine & Trastuzumab (XH) & TucatinibRegimen
1Reported efficacy is based on the 2021 update. Chemotherapy
Targeted therapy
21-day cycles References
Docetaxel & Trastuzumab (TH)TH: Taxotere (Docetaxel) & Herceptin (Trastuzumab) Regimen variant #1, 60 mg/m2 docetaxel
Prior treatment criteria
Chemotherapy
Targeted therapy
21-day cycles Regimen variant #2, 75 mg/m2 docetaxel
Prior treatment criteria
Chemotherapy
Targeted therapy
21-day cycles References
EHPEHP: Eribulin, Herceptin (Trastuzumab), Pertuzumab Regimen
1Results are based on a one-sided statistical analysis. Prior treatment criteria
Chemotherapy
Targeted therapy
21-day cycles References
Eribulin & MargetuximabRegimen
1Reported efficacy is based on the 2022 update. Chemotherapy
Targeted therapy
21-day cycles References
Eribulin & TrastuzumabRegimen
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm. Prior treatment criteria
Chemotherapy
Targeted therapy
21-day cycles References
Gemcitabine & MargetuximabRegimen
1Reported efficacy is based on the 2022 update. Chemotherapy
Targeted therapy
21-day cycles References
Gemcitabine & TrastuzumabRegimen variant #1, 1000/q3wk trastuzumab
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm. Chemotherapy
Targeted therapy
21-day cycles Regimen variant #2, 1200/q3wk trastuzumab
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm. Prior treatment criteria
Chemotherapy
Targeted therapy
21-day cycles Regimen variant #3, weekly trastuzumab
Chemotherapy
Targeted therapy
21-day cycles References
GHPGHP: Gemcitabine, Herceptin (Trastuzumab), Pertuzumab Regimen
1Results are based on a one-sided statistical analysis. Prior treatment criteria
Chemotherapy
Targeted therapy
21-day cycles References
Lapatinib & TrastuzumabRegimen
1Reported efficacy is based on the 2012 update. Targeted therapy
28-day cycles References
Paclitaxel & Trastuzumab (TH)TH: Taxol (Paclitaxel), Herceptin (Trastuzumab) Regimen
Chemotherapy
Targeted therapy
21-day cycles References
Paclitaxel, Pertuzumab, Trastuzumab emtansineRegimen variant #1, q3wk T-DM1
Note: this is the MTD. Chemotherapy
Targeted therapy
Antibody-drug conjugate therapy
21-day cycles Regimen variant #2, weekly T-DM1
Note: this is the MTD. Chemotherapy
Targeted therapy
Antibody-drug conjugate therapy
21-day cycles References
nab-Paclitaxel & TrastuzumabRegimen variant #1
Chemotherapy
Targeted therapy
21-day cycles Regimen variant #2
Chemotherapy
Targeted therapy
21-day cycles References
nab-Paclitaxel, Pertuzumab, TrastuzumabRegimen variant #1
1Results are based on a one-sided statistical analysis. Prior treatment criteria
Chemotherapy
Targeted therapy
21-day cycles Regimen variant #2
1Results are based on a one-sided statistical analysis. Prior treatment criteria
Chemotherapy
Targeted therapy
21-day cycles References
Pertuzumab & TrastuzumabRegimen variant #1, q3wk trastuzumab
Targeted therapy
21-day cycle for 8 cycles Treatment can be continued if there is no progressive disease. Regimen variant #2, weekly trastuzumab
Targeted therapy
21-day cycle for 8 cycles; treatment can be continued if there is no progressive disease References
THP (Docetaxel)THP: Taxotere (Docetaxel), Herceptin (Trastuzumab), Pertuzumab Regimen variant #1
1Results are based on a one-sided statistical analysis. Prior treatment criteria
Chemotherapy
Targeted therapy
21-day cycles Regimen variant #2
1Results are based on a one-sided statistical analysis. Prior treatment criteria
Chemotherapy
Targeted therapy
21-day cycles References
THP (Paclitaxel)THP: Taxol (Paclitaxel), Herceptin (Trastuzumab), Pertuzumab Regimen
1Results are based on a one-sided statistical analysis. Prior treatment criteria
Chemotherapy
Targeted therapy
21-day cycles References
Trastuzumab monotherapyRegimen
Targeted therapyReferences
Trastuzumab deruxtecan monotherapyRegimen
1Reported efficacy is based on the 2022 update. Antibody-drug conjugate therapy
21-day cycles References
Trastuzumab emtansine monotherapyT-DM1: Trastuzumab-DM1 (Trastuzumab emtansine) Example ordersRegimen
1Reported efficacy for EMILIA is based on the 2017 update. Antibody-drug conjugate therapy
21-day cycles References
Vinorelbine & MargetuximabRegimen
1Reported efficacy is based on the 2022 update. Chemotherapy
Targeted therapy
21-day cycles References
VHPVHP: Vinorelbine, Herceptin (Trastuzumab), Pertuzumab Regimen
1Results are based on a one-sided statistical analysis. Prior treatment criteria
Chemotherapy
Targeted therapy
21-day cycles References
Vinorelbine & Trastuzumab (VH)VH: Vinorelbine & Herceptin (Trastuzumab) Regimen variant #1, 2 out of 3 weeks
Note: this is the lower bound of vinorelbine dosing specified in SOPHIA. Prior treatment criteria
Chemotherapy
Targeted therapy
21-day cycles Regimen variant #2, 2 out of 3 weeks
Note: this is the upper bound of vinorelbine dosing specified in SOPHIA. Chemotherapy
Targeted therapy
21-day cycles Regimen variant #3, weekly
Chemotherapy
Targeted therapy
28-day cycles References
Vinorelbine & Trastuzumab (VH) & EverolimusVH & Everolimus: Vinorelbine, Herceptin (Trastuzumab), Everolimus Regimen
Chemotherapy
Targeted therapy
28-day cycles References
XHPXHP: Xeloda (Capecitabine), Herceptin (Trastuzumab), Pertuzumab Regimen
1Results are based on a one-sided statistical analysis. Prior treatment criteria
Chemotherapy
Targeted therapy
21-day cycles References
Maintenance for metastatic or unresectable diseasePertuzumab & TrastuzumabRegimen
Preceding treatment
Targeted therapy
21-day cycles References
Trastuzumab monotherapyRegimen variant #1, q3wk dosing
Preceding treatment
Regimen variant #2, weekly dosing
Preceding treatment
References
Additional resources
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