Breast cancer, HER2-positive
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Note: this page has regimens which are specific to breast cancer that is HER-2 receptor positive. Please see the breast cancer page for other chemotherapy regimens.
123 regimens on this page
203 variants on this page
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Guidelines
ESMO
- Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. PubMed
- 3rd ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3). PubMed
- BRCA in breast cancer: ESMO Clinical Practice Guidelines PubMed
NCCN
Neoadjuvant chemotherapy
AC -> TH
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AC -> TH: Adriamycin (Doxorubicin) & Cyclophosphamide followed by Taxol (Paclitaxel) & Herceptin (Trastuzumab)
AC-TH: Adriamycin (Doxorubicin) & Cyclophosphamide followed by Taxol (Paclitaxel) & Herceptin (Trastuzumab)
AC-T-T: Adriamycin (Doxorubicin) & Cyclophosphamide followed by Taxol (Paclitaxel) & Trastuzumab
Regimen
Study | Evidence | Comparator | Efficacy |
Robidoux et al. 2013 (NSABP B-41) | Phase III | AC -> THL | Might have inferior pCR rate |
AC -> TL | Seems not superior |
Chemotherapy, AC portion
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles, followed by:
Chemotherapy, TH portion
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
- 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, followed by surgery
After surgery, patients proceeded to adjuvant trastuzumab for a total of 52 weeks of therapy.
References
- Robidoux A, Tang G, Rastogi P, Geyer CE Jr, Azar CA, Atkins JN, Fehrenbacher L, Bear HD, Baez-Diaz L, Sarwar S, Margolese RG, Farrar WB, Brufsky AM, Shibata HR, Bandos H, Paik S, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1183-92. Epub 2013 Oct 4. link to original article contains protocol PubMed
AC -> THL
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AC -> THL: Adriamycin (Doxorubicin) & Cyclophosphamide followed by Taxol (Paclitaxel), Herceptin (Trastuzumab), Lapatinib
Regimen
Study | Evidence | Comparator | Efficacy |
Robidoux et al. 2013 (NSABP B-41) | Phase III | AC -> TH | Might have superior pCR rate |
AC -> TL | Might have superior pCR rate |
Chemotherapy, AC portion
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles, followed by:
Chemotherapy, THL portion
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
- 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, followed by surgery
After surgery, patients proceeded to adjuvant trastuzumab for a total of 52 weeks of therapy.
References
- Robidoux A, Tang G, Rastogi P, Geyer CE Jr, Azar CA, Atkins JN, Fehrenbacher L, Bear HD, Baez-Diaz L, Sarwar S, Margolese RG, Farrar WB, Brufsky AM, Shibata HR, Bandos H, Paik S, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1183-92. Epub 2013 Oct 4. link to original article contains protocol PubMed
AC -> TL
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AC -> TL: Adriamycin (Doxorubicin) & Cyclophosphamide followed by Taxol (Paclitaxel) & Lapatinib
Regimen
Study | Evidence | Comparator | Efficacy |
Robidoux et al. 2013 (NSABP B-41) | Phase III | AC -> TH | Seems not superior |
AC -> THL | Might have inferior pCR rate |
Chemotherapy, AC portion
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles, followed by:
Chemotherapy, TL portion
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
- Lapatinib (Tykerb) 1250 mg PO once per day
28-day cycle for 4 cycles, followed by surgery
After surgery, patients proceeded to adjuvant trastuzumab for a total of 52 weeks of therapy.
References
- Robidoux A, Tang G, Rastogi P, Geyer CE Jr, Azar CA, Atkins JN, Fehrenbacher L, Bear HD, Baez-Diaz L, Sarwar S, Margolese RG, Farrar WB, Brufsky AM, Shibata HR, Bandos H, Paik S, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1183-92. Epub 2013 Oct 4. link to original article contains protocol PubMed
Docetaxel, Pertuzumab, Trastuzumab
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Regimen
Study | Evidence | Comparator | Efficacy |
Gianni et al. 2011 (NeoSphere) | Randomized Phase II | Docetaxel & Pertuzumab | Seems not superior |
Pertuzumab & Trastuzumab | Seems not superior | ||
TH | Seems to have superior pCR rate |
Chemotherapy
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycles 2 to 4: 420 mg IV once on day 1
- 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
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- Based on tolerability, investigators could increase dose of Docetaxel (Taxotere) to 100 mg/m2 IV once on day 1
21-day cycle for 4 cycles, then surgery
After surgery, patients were treated with adjuvant FEC & H.
References
- 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 verified protocol PubMed
- 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
TCHP (Docetaxel)
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TCHP: Taxotere (Docetaxel), Carboplatin, Herceptin (Trastuzumab), Pertuzumab
Regimen
Study | Evidence | Comparator | Efficacy |
Schneeweiss et al. 2013 (TRYPHAENA) | Randomized Phase II | FEC & HP -> THP | Not reported |
FEC -> THP | Not reported |
Neoadjuvant chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Trastuzumab (Herceptin) 8 mg/kg IV once on cycle 1 day 1; then on subsequent cycles Trastuzumab (Herceptin) is 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) 840 mg IV once on cycle 1 day 1; then on subsequent cycles Pertuzumab (Perjeta) is 420 mg IV once on day 1
- No dose escalation of Docetaxel (Taxotere) in this arm.
21-day cycle for 6 cycles, then surgery
Post-operative chemotherapy
- Trastuzumab (Herceptin) 6 mg/kg IV once on day 1
- "Further adjuvant treatment (radiotherapy, chemotherapy, hormonal treatment) according to local guidelines."
21-day cycles, to complete 1 year of total therapy with Trastuzumab (Herceptin)
References
- 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. link to original article contains verified protocol PubMed
TH (Taxol) -> AC
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TH -> AC: Taxol (Paclitaxel) & Herceptin (Trastuzumab) followed by Adriamycin (Doxorubicin) & Cyclophosphamide
Regimen
Study | Evidence | Comparator | Efficacy |
Park et al. 2016 (I-SPY 2) | Adaptively Randomized Phase II | Paclitaxel & Neratinib -> AC | Seems to have inferior pCR rate |
TH portion
- Paclitaxel (Taxol) 80 mg/m2 IV once per week
- Trastuzumab (Herceptin) as follows:
- Week 1: 4 mg/kg IV once
- Weeks 2 to 12: 2 mg/kg IV once per week
12-week course, followed by:
AC portion
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 00 mg/m2 IV once on day 1
14- to 21-day cycle for 4 cycles, followed by surgery
References
- 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 verified protocol PubMed
TH (Taxol) -> FEC & H
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TH -> FEC & H: Taxol (Paclitaxel) & Herceptin (Trastuzumab) followed by Fluorouracil, Epirubicin, Cyclophosphamide, Herceptin (Trastuzumab)
Regimen
Study | Evidence | Comparator | Efficacy |
Buzdar et al. 2005 | Randomized | T -> FEC | Seems to have superior pCR rate |
TH portion
- Paclitaxel (Taxol) 225 mg/m2 IV continuous infusion over 24 hours on day 1
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1 prior to first dose of paclitaxel, 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, followed by:
FEC & H portion
- 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
- Trastuzumab (Herceptin) 2 mg/kg IV once per day on days 1, 8, 15
21-day cycle for 4 cycles, followed by surgery
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 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
Adjuvant chemotherapy, HER-2 positive
AC -> T -> H
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AC -> T -> H: Adriamycin (Doxorubicin) & Cyclophosphamide followed by Taxol (Paclitaxel) followed by Herceptin (Trastuzumab)
Regimen
Study | Evidence | Comparator | Efficacy |
Romond et al. 2005 (NCCTG N9831) | Phase III | AC -> T | Superior OS |
AC -> TH | Not reported |
This dosing schema was evaluated in NCCTG N9831 but is not commonly used and is here for reference purposes only.
AC portion
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles, followed by:
T portion
- Paclitaxel (Taxol) 80 mg/m2 IV over 1 hour once per week
12-week course, followed by:
H portion
- Trastuzumab (Herceptin) 4 mg/kg IV loading dose, then 2 mg/kg IV once per week
52-week course
Monitoring
- Cardiac function: echocardiogram at baseline, then every 3 months while on Trastuzumab (Herceptin)
References
- 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
- 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
AC -> TH (Taxol)
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AC -> TH: Adriamycin (Doxorubicin) & Cyclophosphamide followed by Taxol (Paclitaxel) & Herceptin (Trastuzumab)
AC-TH: Adriamycin (Doxorubicin) & Cyclophosphamide followed by Taxol (Paclitaxel) & Herceptin (Trastuzumab)
AC-T-T: Adriamycin (Doxorubicin) & Cyclophosphamide followed by Taxol (Paclitaxel) & Trastuzumab
Regimen
Study | Evidence | Comparator | Efficacy |
Romond et al. 2005 (NSABP B-31/NCCTG N9831) | Phase III | AC -> T | Superior OS |
Chemotherapy, AC portion
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles, followed by:
Chemotherapy, TH portion
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
- 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, followed by:
Chemotherapy, trastuzumab monotherapy
- Trastuzumab (Herceptin) 2 mg/kg IV once per week
40 additional weeks to complete a total of 52 weeks of therapy
References
- 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
- 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
AC -> TH (Taxotere)
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AC -> TH: Adriamycin (Doxorubicin) & Cyclophosphamide followed by Taxotere (Docetaxel) & Herceptin (Trastuzumab)
Regimen
Study | Evidence | Comparator | Efficacy |
Slamon et al. 2011 (BCIRG 006) | Phase III | AC -> T | Superior OS |
TCH | Seems not superior |
AC portion
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles, followed by:
TH portion
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
- 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, followed by:
- Trastuzumab (Herceptin) 6 mg/kg IV once on day 1
3-week cycle for 14 additional cycles to complete a total of 52 weeks of therapy
Monitoring
- Cardiac function: echocardiogram at baseline, then every 3 months while on Trastuzumab (Herceptin)
References
- Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J; Breast Cancer International Research Group. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011 Oct 6;365(14):1273-83. link to original article PubMed
ddAC -> H
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ddAC -> H: dose-dense Adriamycin (Doxorubicin) & Cyclophosphamide followed by Herceptin (Trastuzumab)
Regimen
Study | Evidence | Comparator | Efficacy |
Shulman et al. 2012 (CALGB 40101) | Phase III | TH | Seems not superior |
T -> H | Seems not superior |
ddAC portion
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Supportive medications
- Recommended growth factor support with one of the following:
- Filgrastim (Neupogen) 5 mcg/kg (rounded to 300 mcg or 480 mcg, whichever is closer) SC on days 3 to 10; may be discontinued before day 10 if ANC has recovered to an "acceptable range, as determined by the treating physician"
- Sargramostim (Leukine) 250 to 500 mcg/m2 SC on days 3 to 10; may be discontinued before day 10 if ANC has recovered to an "acceptable range, as determined by the treating physician"
- Pegfilgrastim (Neulasta) 6 mg SC, administered once 24 to 36 hours after chemotherapy
14-day cycle for 4 cycles; the study protocol originally specified 21-day cycles but was amended to 14-day cycles after results of CALGB 9741 - Citron et al. 2003 were available
Trastuzumab (Herceptin) to begin 3 to 8 weeks after the completion of AC:
H portion
- One of the following doses & schedules of trastuzumab:
- Trastuzumab (Herceptin) 4 mg/kg IV x1 as the loading dose, then 2 mg/kg IV every week thereafter
- Trastuzumab (Herceptin) 8 mg/kg IV x1 as the loading dose, then 6 mg/kg IV every 3 weeks thereafter
52-week course
References
- Shulman LN, Cirrincione CT, Berry DA, Becker HP, Perez EA, O'Regan R, Martino S, Atkins JN, Mayer E, Schneider CJ, Kimmick G, Norton L, Muss H, Winer EP, Hudis C. Six Cycles of Doxorubicin and Cyclophosphamide or Paclitaxel Are Not Superior to Four Cycles As Adjuvant Chemotherapy for Breast Cancer in Women With Zero to Three Positive Axillary Nodes: Cancer and Leukemia Group B 40101. J Clin Oncol. 2012 Nov 20;30(33):4071-6. Epub 2012 Jul 23. link to original article contains verified protocol link to study protocol PDF PubMed
- Update: Shulman LN, Berry DA, Cirrincione CT, Becker HP, Perez EA, O'Regan R, Martino S, Shapiro CL, Schneider CJ, Kimmick G, Burstein HJ, Norton L, Muss H, Hudis CA, Winer EP. Comparison of doxorubicin and cyclophosphamide versus single-agent paclitaxel as adjuvant therapy for breast cancer in women with 0 to 3 positive axillary nodes: CALGB 40101 (Alliance). J Clin Oncol. 2014 Aug 1;32(22):2311-7. link to PMC article PubMed
ddAC -> PT
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ddAC -> PT: dose-dense Adriamycin (Doxorubicin) & Cyclophosphamide followed by Paclitaxel & Trastuzumab
Regimen
Study | Evidence |
Dang et al. 2008 | Phase II |
ddAC portion
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
14-day cycle for 4 cycles, followed by:
PT portion
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once with first dose of paclitaxel, then 2 mg/kg IV once on day 8
- Cycles 2 to 4: 2 mg/kg IV once per day on days 1 & 8
14-day cycle for 4 cycles, followed by:
- EITHER Trastuzumab (Herceptin) 2 mg/kg IV, 1-week cycle for 44 additional cycles/weeks to complete a total of 52 weeks of therapy
- OR Trastuzumab (Herceptin) 6 mg/kg IV, 3-week cycle for 15 additional cycles/weeks to complete a total of 52 weeks of therapy
Supportive medications
All chemotherapy cycles given with Filgrastim (Neupogen) support
Monitoring
- Cardiac function: echocardiogram at baseline, then every 3 months while on Trastuzumab (Herceptin)
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 PubMed
FEC & H
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Regimen
Study | Evidence |
Gianni et al. 2011 (NeoSphere) | Non-randomized portion of RCT |
Treatment preceded by neoadjuvant docetaxel & pertuzumab versus neoadjuvant docetaxel, pertuzumab, trastuzumab versus neoadjuvant pertuzumab & trastuzumab versus neoadjvuant TH.
Chemotherapy
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
- Trastuzumab (Herceptin) 6 mg/kg IV once on day 1
21-day cycle for 3 cycles, followed by:
- Trastuzumab (Herceptin) 6 mg/kg IV once on day 1
- Radiation therapy and/or hormone therapy for ER positive patients is given "per local guidelines"
21-day cycles, to complete 1 year of total therapy with trastuzumab
References
- 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 verified protocol PubMed
- 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
TCH (Carboplatin)
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TCH: Taxotere (Docetaxel), Carboplatin, Herceptin (Trastuzumab)
Regimen
Study | Evidence | Comparator | Efficacy |
Slamon et al. 2011 (BCIRG 006) | Phase III | AC -> T | Seems to have superior OS |
AC -> TH | Seems not superior |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 2 to 6: 2 mg/kg IV once per day on days 1, 8, 15
21-day cycle for 6 cycles, followed by:
- Trastuzumab (Herceptin) 6 mg/kg IV once on day 1
3-week cycle for 12 additional cycles to complete a total of 52 weeks of therapy
Monitoring
- Cardiac function: echocardiogram at baseline, then every 3 months while on Trastuzumab (Herceptin)
References
- Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J; Breast Cancer International Research Group. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011 Oct 6;365(14):1273-83. link to original article PubMed
TCH (Cyclophosphamide)
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TCH: Taxotere, Cyclophosphamide, Herceptin
Regimen
Study | Evidence |
Jones et al. 2013 | Phase II |
Induction therapy
Chemotherapy started within 84 days of surgery.
- Docetaxel (Taxotere) 75 mg/m2 IV over 1 hour once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV over 15 to 30 minutes once on day 1
- Trastuzumab (Herceptin) 4 mg/kg IV over 90 minutes once on cycle 1 day 1; then Trastuzumab (Herceptin) 2 mg/kg IV over 30 to 60 minutes once per day on cycle 1 days 8 & 15; then Trastuzumab (Herceptin) 2 mg/kg IV over 30 to 60 minutes once per day on days 1, 8, 15 of cycles 2 and on
Supportive medications
- Use of Filgrastim (Neupogen) or Pegfilgrastim (Neulasta) was allowed.
- Prophylactic antibiotics were not recommended.
21-day cycle for 4 cycles, then proceed to trastuzumab monotherapy
Trastuzumab monotherapy
- Trastuzumab (Herceptin) 6 mg/kg IV once on day 1
21-day cycles, given until patient receives 1 year total of trastuzumab therapy
References
- Jones SE, Collea R, Paul D, Sedlacek S, Favret AM, Gore I Jr, Lindquist DL, Holmes FA, Allison MA, Brooks BD, Portillo RM, Vukelja SJ, Steinberg MS, Stokoe C, Crockett MW, Wang Y, Asmar L, Robert NJ, O'Shaughnessy J. Adjuvant docetaxel and cyclophosphamide plus trastuzumab in patients with HER2-amplified early stage breast cancer: a single-group, open-label, phase 2 study. Lancet Oncol. 2013 Oct;14(11):1121-8. Epub 2013 Sep 2. link to original article contains verified protocol PubMed
TH
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TH: Taxol (Paclitaxel), Herceptin (Trastuzumab)
Regimen
Study | Evidence | Comparator | Efficacy |
Shulman et al. 2012 (CALGB 40101) | Phase III | ddAC -> H | Seems not superior |
T -> H | Seems not superior |
TH portion
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once on day 8
- Cycles 2 to 4: 2 mg/kg IV once per day on days 1 & 8
Supportive medications
- Diphenhydramine (Benadryl) 12.5-50 mg IV once 30 to 60 minutes prior to paclitaxel
- One of the following H2 blockers:
- Ranitidine (Zantac) 50 mg IV once 30 to 60 minutes prior to paclitaxel
- Cimetidine (Tagamet) 300 mg IV once 30 to 60 minutes prior to paclitaxel
- Famotidine (Pepcid) 20 mg IV once 30 to 60 minutes prior to paclitaxel
- One of the following dexamethasone choices:
- Dexamethasone (Decadron) 10 mg IV once at least 60 minutes prior to paclitaxel
- Dexamethasone (Decadron) 10 mg PO once at least 60 minutes prior to paclitaxel
- Dexamethasone (Decadron) 20 mg PO 6 hours and 12 hours prior to paclitaxel
- Recommended growth factor support with one of the following:
- Filgrastim (Neupogen) 5 mcg/kg (rounded to 300 mcg or 480 mcg, whichever is closer) SC once per day on days 3 to 10; may be discontinued before day 10 if ANC has recovered to an "acceptable range, as determined by the treating physician"
- Sargramostim (Leukine) 250 to 500 mcg/m2 SC once per day on days 3 to 10; may be discontinued before day 10 if ANC has recovered to an "acceptable range, as determined by the treating physician"
- Pegfilgrastim (Neulasta) 6 mg SC once, given 24 to 36 hours after chemotherapy
14-day cycle for 4 cycles, followed by:
Trastuzumab monotherapy
- One of the following doses & schedules of trastuzumab:
- Trastuzumab (Herceptin) 2 mg/kg IV once per week
- Trastuzumab (Herceptin) 6 mg/kg IV once every 3 weeks
44-week course, which, counting doses given as part of TH, will result in a total of 52 weeks of trastuzumab therapy
Regimen #2
Study | Evidence |
Tolaney et al. 2015 (APT) | Phase II |
TH portion
- Paclitaxel (Taxol) 80 mg/m2 IV once per week
- Trastuzumab (Herceptin) 4 mg/kg IV once on day 1 with the first dose of paclitaxel, then 2 mg/kg IV once per week thereafter
12-week course, then proceed to trastuzumab only phase
Trastuzumab monotherapy
- One of the following:
- Trastuzumab (Herceptin) 2 mg/kg IV once per day on days 1, 8, 15
- Trastuzumab (Herceptin) 6 mg/kg IV once on day 1
3-week cycle for 13 additional cycles (for 39 weeks of trastuzumab only therapy)
References
- Shulman LN, Cirrincione CT, Berry DA, Becker HP, Perez EA, O'Regan R, Martino S, Atkins JN, Mayer E, Schneider CJ, Kimmick G, Norton L, Muss H, Winer EP, Hudis C. Six Cycles of Doxorubicin and Cyclophosphamide or Paclitaxel Are Not Superior to Four Cycles As Adjuvant Chemotherapy for Breast Cancer in Women With Zero to Three Positive Axillary Nodes: Cancer and Leukemia Group B 40101. J Clin Oncol. 2012 Nov 20;30(33):4071-6. Epub 2012 Jul 23. link to original article contains verified protocol link to study protocol PDF PubMed
- Update: Shulman LN, Berry DA, Cirrincione CT, Becker HP, Perez EA, O'Regan R, Martino S, Shapiro CL, Schneider CJ, Kimmick G, Burstein HJ, Norton L, Muss H, Hudis CA, Winer EP. Comparison of doxorubicin and cyclophosphamide versus single-agent paclitaxel as adjuvant therapy for breast cancer in women with 0 to 3 positive axillary nodes: CALGB 40101 (Alliance). J Clin Oncol. 2014 Aug 1;32(22):2311-7. link to PMC article PubMed
- Tolaney SM, Barry WT, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS, Ellis M, Shapira I, Wolff AC, Carey LA, Overmoyer BA, Partridge AH, Guo H, Hudis CA, Krop IE, Burstein HJ, Winer EP. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. N Engl J Med. 2015 Jan 8;372(2):134-41. Erratum in: N Engl J Med. 2015 Nov 12;373(20):1989. link to original article PubMed
T -> H
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T -> H: Sequential Taxol (Paclitaxel), Herceptin (Trastuzumab)
Regimen
Study | Evidence | Comparator | Efficacy |
Shulman et al. 2012 (CALGB 40101) | Phase III | ddAC -> H | Seems not superior |
TH | Seems not superior |
T portion
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
Supportive medications
- Diphenhydramine (Benadryl) 12.5 to 50 mg IV once 30 to 60 minutes prior to paclitaxel
- One of the following H2 blockers:
- Ranitidine (Zantac) 50 mg IV once 30 to 60 minutes prior to paclitaxel
- Cimetidine (Tagamet) 300 mg IV once 30 to 60 minutes prior to paclitaxel
- Famotidine (Pepcid) 20 mg IV once 30 to 60 minutes prior to paclitaxel
- One of the following dexamethasone choices:
- Dexamethasone (Decadron) 10 mg IV once at least 60 minutes prior to paclitaxel
- Dexamethasone (Decadron) 10 mg PO once at least 60 minutes prior to paclitaxel
- Dexamethasone (Decadron) 20 mg PO 6 hours and 12 hours prior to paclitaxel
- Recommended growth factor support with one of the following:
- Filgrastim (Neupogen) 5 mcg/kg (rounded to 300 mcg or 480 mcg, whichever is closer) SC once per day on days 3 to 10; may be discontinued before day 10 if ANC has recovered to an "acceptable range, as determined by the treating physician"
- Sargramostim (Leukine) 250 to 500 mcg/m2 SC once per day on days 3 to 10; may be discontinued before day 10 if ANC has recovered to an "acceptable range, as determined by the treating physician"
- Pegfilgrastim (Neulasta) 6 mg SC once, given 24 to 36 hours after chemotherapy
14-day cycle for 4 cycles, followed by:
Trastuzumab monotherapy
One of the following doses & schedules of trastuzumab:
- Trastuzumab (Herceptin) 4 mg/kg IV once as the loading dose, then 2 mg/kg IV once per week thereafter
- Trastuzumab (Herceptin) 8 mg/kg IV once as the loading dose, then 6 mg/kg IV every 3 weeks thereafter
52-week course of therapy
References
- Shulman LN, Cirrincione CT, Berry DA, Becker HP, Perez EA, O'Regan R, Martino S, Atkins JN, Mayer E, Schneider CJ, Kimmick G, Norton L, Muss H, Winer EP, Hudis C. Six Cycles of Doxorubicin and Cyclophosphamide or Paclitaxel Are Not Superior to Four Cycles As Adjuvant Chemotherapy for Breast Cancer in Women With Zero to Three Positive Axillary Nodes: Cancer and Leukemia Group B 40101. J Clin Oncol. 2012 Nov 20;30(33):4071-6. Epub 2012 Jul 23. link to original article contains verified protocol link to study protocol PDF PubMed
- Update: Shulman LN, Berry DA, Cirrincione CT, Becker HP, Perez EA, O'Regan R, Martino S, Shapiro CL, Schneider CJ, Kimmick G, Burstein HJ, Norton L, Muss H, Hudis CA, Winer EP. Comparison of doxorubicin and cyclophosphamide versus single-agent paclitaxel as adjuvant therapy for breast cancer in women with 0 to 3 positive axillary nodes: CALGB 40101 (Alliance). J Clin Oncol. 2014 Aug 1;32(22):2311-7. link to PMC article PubMed
TH (Taxotere) -> FEC
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TH -> FEC: Taxotere (Docetaxel) & Herceptin (Trastuzumab) followed by Fluorouracil, Epirubicin, Cyclophosphamide
Regimen
Study | Evidence | Comparator | Efficacy |
Joensuu et al. 2006 (FinHer) | Phase III | T -> FEC V -> FEC |
Seems not superior |
VH -> FEC | Not reported |
TH portion
- Docetaxel (Taxotere) 100 mg/m2 IV over 1 hour once on day 1
- 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
21-day cycle for 3 cycles, followed by:
FEC portion
- 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 3 cycles
Monitoring
- Cardiac function: echocardiogram at baseline, after last cycle of FEC, 12 months after completion of chemotherapy, and 36 months after completion of chemotherapy
References
- 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
- 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
VH -> FEC
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VH -> FEC: Vinorelbine & Herceptin (Trastuzumab) followed by Fluorouracil, Epirubicin, Cyclophosphamide
Regimen
Study | Evidence | Comparator | Efficacy |
Joensuu et al. 2006 (FinHer) | Phase III | T -> FEC V -> FEC |
Seems not superior |
TH -> FEC | Not reported |
VH portion
- Vinorelbine (Navelbine) 24 mg/m2 IV over 5 to 10 minutes once per day on days 1, 8, 15
- 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
21-day cycle for 3 cycles, followed by:
FEC portion
- 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 3 cycles
Monitoring
- Cardiac function: echocardiogram at baseline, after last cycle of FEC, 12 months after completion of chemotherapy, and 36 months after completion of chemotherapy
References
- 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
- 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
Trastuzumab (Herceptin)
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Regimen #1, 1-year course
Study | Evidence | Comparator | Efficacy |
Piccart-Gebhart et al. 2005 (HERA/BIG 01-01) | Phase III | No trastuzumab after (neo-)adjuvant chemotherapy | Superior OS |
Trastuzumab x 2 years | Seems not superior |
Participants in HERA had already received at least four courses of an approved (neo-)adjuvant chemotherapy regimen. See supplement for a list of these regimens.
Chemotherapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV over 90 minutes once on day 1
- Cycle 2 onwards: 6 mg/kg IV over 90 minutes once on day 1
3-week cycle for 1 year
Regimen #2, 2-year course
Study | Evidence | Comparator | Efficacy |
Piccart-Gebhart et al. 2005 (HERA/BIG 01-01) | Phase III | No trastuzumab after (neo-)adjuvant chemotherapy | Not reported |
Trastuzumab x 1 year | Seems not superior |
Participants in HERA had already received at least four courses of an approved (neo-)adjuvant chemotherapy regimen. See supplement for a list of these regimens.
Chemotherapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV over 90 minutes once on day 1
- Cycle 2 onwards: 6 mg/kg IV over 90 minutes once on day 1
3-week cycle for 2 years
References
- Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C, Cameron D, Dowsett M, Barrios CH, Steger G, Huang CS, Andersson M, Inbar M, Lichinitser M, Láng I, Nitz U, Iwata H, Thomssen C, Lohrisch C, Suter TM, Rüschoff J, Suto T, Greatorex V, Ward C, Straehle C, McFadden E, Dolci MS, Gelber RD; Herceptin Adjuvant (HERA) Trial Study Team. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1659-72. link to original article contains verified protocol [link to data supplement] PubMed
- Update: Smith I, Procter M, Gelber RD, Guillaume S, Feyereislova A, Dowsett M, Goldhirsch A, Untch M, Mariani G, Baselga J, Kaufmann M, Cameron D, Bell R, Bergh J, Coleman R, Wardley A, Harbeck N, Lopez RI, Mallmann P, Gelmon K, Wilcken N, Wist E, Sánchez Rovira P, Piccart-Gebhart MJ; HERA study team. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet. 2007 Jan 6;369(9555):29-36. link to original article contains verified protocol PubMed
- Update: Gianni L, Dafni U, Gelber RD, Azambuja E, Muehlbauer S, Goldhirsch A, Untch M, Smith I, Baselga J, Jackisch C, Cameron D, Mano M, Pedrini JL, Veronesi A, Mendiola C, Pluzanska A, Semiglazov V, Vrdoljak E, Eckart MJ, Shen Z, Skiadopoulos G, Procter M, Pritchard KI, Piccart-Gebhart MJ, Bell R; Herceptin Adjuvant (HERA) Trial Study Team. Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncol. 2011 Mar;12(3):236-44. Epub 2011 Feb 25. link to original article contains verified protocol PubMed
- Update: Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, de Azambuja E, Procter M, Suter TM, Jackisch C, Cameron D, Weber HA, Heinzmann D, Dal Lago L, McFadden E, Dowsett M, Untch M, Gianni L, Bell R, Köhne CH, Vindevoghel A, Andersson M, Brunt AM, Otero-Reyes D, Song S, Smith I, Leyland-Jones B, Baselga J; Herceptin Adjuvant (HERA) Trial Study Team. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet. 2013 Sep 21;382(9897):1021-8. link to SD article PubMed
- Update: Cameron D, Piccart-Gebhart MJ, Gelber RD, Procter M, Goldhirsch A, de Azambuja E, Castro G Jr, Untch M, Smith I, Gianni L, Baselga J, Al-Sakaff N, Lauer S, McFadden E, Leyland-Jones B, Bell R, Dowsett M, Jackisch C; Herceptin Adjuvant (HERA) Trial Study Team. 11 years' follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017 Mar 25;389(10075):1195-1205. Epub 2017 Feb 17. link to original article PubMed
Metastatic disease, HER-2 positive
ACH
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ACH: Adriamycin (Doxorubicin), Cyclophosphamide, Herceptin (Trastuzumab)
Regimen
Study | Evidence | Comparator | Efficacy |
Slamon et al. 2001 | Phase III | AC | Seems to have superior OS |
Note: patients had not previously received adjuvant (postoperative) therapy with an anthracycline. Not commonly used; here for reference purposes only.
Chemotherapy
References
- Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001 Mar 15;344(11):783-92. link to original article PubMed
Ado-trastuzumab emtansine (Kadcyla)
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Example orders
Regimen
Study | Evidence | Comparator | Efficacy |
Verma et al. 2012 (EMILIA) | Phase III | Capecitabine & Lapatinib | Superior OS |
Hurvitz et al. 2013 | Randomized Phase II | TH | Seems to have superior PFS |
Krop et al. 2014 (TH3RESA) | Phase III | Physician's choice | Superior OS (*) |
Note: reported efficacy for TH3RESA is based on the 2017 update.
Chemotherapy
- Ado-trastuzumab emtansine (Kadcyla) 3.6 mg/kg IV once on day 1
21-day cycles, given until progression of disease or unacceptable toxicity
References
- Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh DY, Diéras V, Guardino E, Fang L, Lu MW, Olsen S, Blackwell K; EMILIA Study Group. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012 Nov 8;367(19):1783-91. Epub 2012 Oct 1. Erratum in: N Engl J Med. 2013 Jun 20;368(25):2442. link to original article contains verified protocol PubMed
- Update: Diéras V, Miles D, Verma S, Pegram M, Welslau M, Baselga J, Krop IE, Blackwell K, Hoersch S, Xu J, Green M, Gianni L. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2017 Jun;18(6):732-742. Epub 2017 May 16. link to original articlePubMed
- Hurvitz SA, Dirix L, Kocsis J, Bianchi GV, Lu J, Vinholes J, Guardino E, Song C, Tong B, Ng V, Chu YW, Perez EA. Phase II Randomized Study of Trastuzumab Emtansine Versus Trastuzumab Plus Docetaxel in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer. J Clin Oncol. 2013 Mar 20;31(9):1157-63. Epub 2013 Feb 4. Erratum in: J Clin Oncol. 2013 Aug 10;31(23):2977. link to original article contains verified protocol PubMed
- Krop IE, Kim SB, González-Martín A, LoRusso PM, Ferrero JM, Smitt M, Yu R, Leung AC, Wildiers H; TH3RESA study collaborators. Trastuzumab emtansine versus treatment of physician's choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014 Jun;15(7):689-99. Epub 2014 May 2. link to original article contains protocol PubMed
- Update: Krop IE, Kim SB, Martin AG, LoRusso PM, Ferrero JM, Badovinac-Crnjevic T, Hoersch S, Smitt M, Wildiers H. Trastuzumab emtansine versus treatment of physician's choice in patients with previously treated HER2-positive metastatic breast cancer (TH3RESA): final overall survival results from a randomised open-label phase 3 trial. Lancet Oncol. 2017 Jun;18(6):743-754. Epub 2017 May 16. link to original articlePubMed
Bevacizumab, Capecitabine, Trastuzumab
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Regimen
Study | Evidence |
Martín et al. 2012 | Phase II |
Chemotherapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
- Capecitabine (Xeloda) 1000 mg/m2 PO BID on days 1 to 14
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles, given until progression of disease or unacceptable toxicity
References
- Martín M, Makhson A, Gligorov J, Lichinitser M, Lluch A, Semiglazov V, Scotto N, Mitchell L, Tjulandin S. Phase II study of bevacizumab in combination with trastuzumab and capecitabine as first-line treatment for HER-2-positive locally recurrent or metastatic breast cancer. Oncologist. 2012;17(4):469-75. Epub 2012 Mar 30. link to original article contains verified protocol [1]
- A Study of Avastin (Bevacizumab) in Combination With Herceptin (Trastuzumab) and Xeloda (Capecitabine) in Patients With HER2-Positive Breast Cancer at ClinicalTrials.gov, NCT00811135
Capecitabine & Lapatinib
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Regimen
Study | Evidence | Comparator | Efficacy |
Geyer et al. 2006 | Phase III | Capecitabine | Superior TTP |
Verma et al. 2012 (EMILIA) | Phase III | T-DM1 | Inferior OS |
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO BID days 1 to 14
- Lapatinib (Tykerb) 1250 mg PO once per day
21-day cycles
References
- Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006 Dec 28;355(26):2733-43. link to original article PubMed
- Update: Cameron D, Casey M, Press M, Lindquist D, Pienkowski T, Romieu CG, Chan S, Jagiello-Gruszfeld A, Kaufman B, Crown J, Chan A, Campone M, Viens P, Davidson N, Gorbounova V, Raats JI, Skarlos D, Newstat B, Roychowdhury D, Paoletti P, Oliva C, Rubin S, Stein S, Geyer CE. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat. 2008 Dec;112(3):533-43. link to original article PubMed
- Update: Cameron D, Casey M, Oliva C, Newstat B, Imwalle B, Geyer CE. Lapatinib plus capecitabine in women with HER-2-positive advanced breast cancer: final survival analysis of a phase III randomized trial. Oncologist. 2010;15(9):924-34. link to original article PubMed
- Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh DY, Diéras V, Guardino E, Fang L, Lu MW, Olsen S, Blackwell K; EMILIA Study Group. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012 Nov 8;367(19):1783-91. Epub 2012 Oct 1. Erratum in: N Engl J Med. 2013 Jun 20;368(25):2442. link to original article contains verified protocol PubMed
- Update: Diéras V, Miles D, Verma S, Pegram M, Welslau M, Baselga J, Krop IE, Blackwell K, Hoersch S, Xu J, Green M, Gianni L. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2017 Jun;18(6):732-742. Epub 2017 May 16. link to original articlePubMed
ECH
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ECH: Epirubicin, Cyclophosphamide, Herceptin (Trastuzumab)
Regimen
Study | Evidence | Comparator | Efficacy |
Slamon et al. 2001 | Phase III | EC | Seems to have superior OS |
Not commonly used; here for reference purposes only.
Chemotherapy
References
- Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001 Mar 15;344(11):783-92. link to original article PubMed
Lapatinib (Tykerb)
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Regimen
Study | Evidence | Comparator | Efficacy |
Blackwell et al. 2010 (EGF104900) | Phase III | Lapatinib & Trastuzumab | Seems to have inferior OS |
Chemotherapy
- Lapatinib (Tykerb) 1500 mg PO once per day
(presumably) given until progression of disease or unacceptable toxicity
References
- Blackwell KL, Burstein HJ, Storniolo AM, Rugo H, Sledge G, Koehler M, Ellis C, Casey M, Vukelja S, Bischoff J, Baselga J, O'Shaughnessy J. Randomized study of Lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol. 2010 Mar 1;28(7):1124-30. Epub 2010 Feb 1. link to original article PubMed
- Update: Blackwell KL, Burstein HJ, Storniolo AM, Rugo HS, Sledge G, Aktan G, Ellis C, Florance A, Vukelja S, Bischoff J, Baselga J, O'Shaughnessy J. Overall survival benefit with lapatinib in combination with trastuzumab for patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: final results from the EGF104900 Study. J Clin Oncol. 2012 Jul 20;30(21):2585-92. Epub 2012 Jun 11. link to original article PubMed
Lapatinib & Trastuzumab
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Regimen
Study | Evidence | Comparator | Efficacy |
Blackwell et al. 2010 (EGF104900) | Phase III | Lapatinib | Seems to have superior OS |
Chemotherapy
- Lapatinib (Tykerb) 1000 mg PO once per day
- Trastuzumab (Herceptin) 4 mg/kg IV once on day 1 as a loading dose, then 2 mg/kg IV once per week thereafter
(presumably) given until progression of disease or unacceptable toxicity
References
- Blackwell KL, Burstein HJ, Storniolo AM, Rugo H, Sledge G, Koehler M, Ellis C, Casey M, Vukelja S, Bischoff J, Baselga J, O'Shaughnessy J. Randomized study of Lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol. 2010 Mar 1;28(7):1124-30. Epub 2010 Feb 1. link to original article PubMed
- Update: Blackwell KL, Burstein HJ, Storniolo AM, Rugo HS, Sledge G, Aktan G, Ellis C, Florance A, Vukelja S, Bischoff J, Baselga J, O'Shaughnessy J. Overall survival benefit with lapatinib in combination with trastuzumab for patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: final results from the EGF104900 Study. J Clin Oncol. 2012 Jul 20;30(21):2585-92. Epub 2012 Jun 11. link to original article PubMed
Pertuzumab & Trastuzumab
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Regimen #1, q3wk trastuzumab
Study | Evidence |
Baselga et al. 2010 | Phase II |
Chemotherapy
- Pertuzumab (Perjeta) as follows, given second:
- Cycle 1: 840 mg IV once on day 2
- Cycle 2 onwards: 420 mg IV once on day 1,
- Trastuzumab (Herceptin) as follows:
- Loading dose: 8 mg/kg IV once on day -28 (that is, 28 days before the start of cycle 1)
- Cycle 1 onwards: 6 mg/kg IV once on day 1, given first
21-day cycle for 8 cycles
Treatment can be continued if there is no progressive disease.
Regimen #2, weekly trastuzumab
Study | Evidence |
Baselga et al. 2010 | Phase II |
Chemotherapy
Loading dose:
- Trastuzumab (Herceptin) 4 mg/kg IV once on day -28 (that is, 28 days before the start of cycle 1)
Cycles 1 to 8:
- Pertuzumab (Perjeta) as follows, given second:
- Cycle 1: 840 mg IV once on day 2
- Cycle 2 onwards: 420 mg IV once on day 1,
- Trastuzumab (Herceptin) 2 mg/kg IV once per day on days 1, 8, 15, given first
21-day cycle for 8 cycles; treatment can be continued if there is no progressive disease
References
- Baselga J, Gelmon KA, Verma S, Wardley A, Conte P, Miles D, Bianchi G, Cortes J, McNally VA, Ross GA, Fumoleau P, Gianni L. Phase II trial of pertuzumab and trastuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer that progressed during prior trastuzumab therapy. J Clin Oncol. 2010 Mar 1;28(7):1138-44. Epub 2010 Feb 1. link to original article contains verified protocol PubMed
TCH (Docetaxel)
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TCH: Taxotere (Docetaxel), Carboplatin, Herceptin (Trastuzumab)
Regimen
Study | Evidence | Comparator | Efficacy |
Valero et al. 2011 (BCIRG 007) | Phase III | TH | Seems not superior |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Trastuzumab (Herceptin) 4 mg/kg IV once on cycle 1 day 1, then 2 mg/kg IV once per week during chemotherapy
21-day cycle for 8 cycles, followed by:
- Trastuzumab (Herceptin) 6 mg/kg IV once every 3 weeks until progression
References
- Valero V, Forbes J, Pegram MD, Pienkowski T, Eiermann W, von Minckwitz G, Roche H, Martin M, Crown J, Mackey JR, Fumoleau P, Rolski J, Mrsic-Krmpotic Z, Jagiello-Gruszfeld A, Riva A, Buyse M, Taupin H, Sauter G, Press MF, Slamon DJ. Multicenter phase III randomized trial comparing docetaxel and trastuzumab with docetaxel, carboplatin, and trastuzumab as first-line chemotherapy for patients with HER2-gene-amplified metastatic breast cancer (BCIRG 007 study): two highly active therapeutic regimens. J Clin Oncol. 2011 Jan 10;29(2):149-56. Epub 2010 Nov 29. link to original article contains verified protocol PubMed
TCH (Paclitaxel)
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TCH: Taxol (Paclitaxel), Carboplatin, Herceptin (Trastuzumab)
TPC: Trastuzumab, Paclitaxel, Carboplatin
Regimen
Study | Evidence | Comparator | Efficacy |
Robert et al. 2006 | Phase III | TP | Seems to have superior PFS |
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 2
- Carboplatin (Paraplatin) AUC 6 IV once on day 2
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycle 2 onwards: 2 mg/kg IV once per day on days 1, 8, 15
21-day cycle for at least 6 cycles, followed by:
- Trastuzumab (Herceptin) 2 mg/kg IV once per day on days 1, 8, 15
21-day cycles until progression or intolerance
Monitoring
- Cardiac function: echocardiogram at baseline, then every 3 months while on Trastuzumab (Herceptin)
References
- Perez EA, Suman VJ, Rowland KM, Ingle JN, Salim M, Loprinzi CL, Flynn PJ, Mailliard JA, Kardinal CG, Krook JE, Thrower AR, Visscher DW, Jenkins RB. Two concurrent phase II trials of paclitaxel/carboplatin/trastuzumab (weekly or every-3-week schedule) as first-line therapy in women with HER2-overexpressing metastatic breast cancer: NCCTG study 983252. Clin Breast Cancer. 2005 Dec;6(5):425-32. link to original article PubMed
- Robert N, Leyland-Jones B, Asmar L, Belt R, Ilegbodu D, Loesch D, Raju R, Valentine E, Sayre R, Cobleigh M, Albain K, McCullough C, Fuchs L, Slamon D. Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer. J Clin Oncol. 2006 Jun 20;24(18):2786-92. link to original article PubMed
TH (Paclitaxel)
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TH: Taxol (Paclitaxel), Herceptin (Trastuzumab)
TP: Trastuzumab, Paclitaxel
Regimen #1, weekly paclitaxel (3 weeks on, 1 week off)
Study | Evidence | Comparator | Efficacy |
Hurvitz et al. 2015 (BOLERO-1) | Phase III | Everolimus, Paclitaxel, Trastuzumab | Seems not superior |
Awada et al. 2016 (NEfERT-T) | Phase III | Neratinib & Paclitaxel | Seems not superior |
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22
- Cycle 2 onwards: 2 mg/kg IV once per day on days 1, 8, 15, 22
4-week cycles, continued until progression or intolerance
Regimen #2, q3wk paclitaxel
Study | Evidence | Comparator | Efficacy |
Slamon et al. 2001 | Phase III | Paclitaxel | Seems to have superior OS |
Robert et al. 2006 | Phase III | TPC | Seems to have inferior PFS |
Seidman et al. 2008 (CALGB 9840) | Phase III | TH, weekly paclitaxel (80 mg/m2) | Inferior OS |
Chemotherapy, initial
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 2
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycle 2 onwards: 2 mg/kg IV once per day on days 1, 8, 15
21-day cycle for at least 6 cycles, followed by:
Chemotherapy, maintenance
- Trastuzumab (Herceptin) 2 mg/kg IV once per day on days 1, 8, 15
21-day cycles until progression or intolerance
Monitoring
- Cardiac function: echocardiogram at baseline, then every 3 months while on Trastuzumab (Herceptin)
Regimen #3, weekly paclitaxel (80 mg/m2)
Study | Evidence | Comparator | Efficacy |
Burstein et al. 2007 (TRAVIOTA) | Phase III | Trastuzumab & Vinorelbine | Might have inferior TTP |
Seidman et al. 2008 (CALGB 9840) | Phase III | TH, q3wk paclitaxel | Superior OS |
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per week
- Trastuzumab (Herceptin) 4 mg/kg IV once on day 1, then 2 mg/kg IV once per week, with paclitaxel
8-week cycles
Regimen #4, weekly paclitaxel (90 mg/m2)
Study | Evidence |
Seidman et al. 2001 | Phase II |
Chemotherapy
- Paclitaxel (Taxol) 90 mg/m2 IV once per week
- Trastuzumab (Herceptin) 4 mg/kg IV once on day 0 (prior to first dose of paclitaxel), then 2 mg/kg IV once per week, with paclitaxel
Given until progression
References
- Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001 Mar 15;344(11):783-92. link to original article PubMed
- Seidman AD, Fornier MN, Esteva FJ, Tan L, Kaptain S, Bach A, Panageas KS, Arroyo C, Valero V, Currie V, Gilewski T, Theodoulou M, Moynahan ME, Moasser M, Sklarin N, Dickler M, D'Andrea G, Cristofanilli M, Rivera E, Hortobagyi GN, Norton L, Hudis CA. Weekly trastuzumab and paclitaxel therapy for metastatic breast cancer with analysis of efficacy by HER2 immunophenotype and gene amplification. J Clin Oncol. 2001 May 15;19(10):2587-95. link to original article PubMed
- Robert N, Leyland-Jones B, Asmar L, Belt R, Ilegbodu D, Loesch D, Raju R, Valentine E, Sayre R, Cobleigh M, Albain K, McCullough C, Fuchs L, Slamon D. Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer. J Clin Oncol. 2006 Jun 20;24(18):2786-92. link to original article PubMed
- Burstein HJ, Keshaviah A, Baron AD, Hart RD, Lambert-Falls R, Marcom PK, Gelman R, Winer EP. Trastuzumab plus vinorelbine or taxane chemotherapy for HER2-overexpressing metastatic breast cancer: the trastuzumab and vinorelbine or taxane study. Cancer. 2007 Sep 1;110(5):965-72. link to original article PubMed
- Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom PK, Gipson G, Burstein H, Lake D, Shapiro CL, Ungaro P, Norton L, Winer E, Hudis C. Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol. 2008 Apr 1;26(10):1642-9. link to original article PubMed
- Hurvitz SA, Andre F, Jiang Z, Shao Z, Mano MS, Neciosup SP, Tseng LM, Zhang Q, Shen K, Liu D, Dreosti LM, Burris HA, Toi M, Buyse ME, Cabaribere D, Lindsay MA, Rao S, Pacaud LB, Taran T, Slamon D. Combination of everolimus with trastuzumab plus paclitaxel as first-line treatment for patients with HER2-positive advanced breast cancer (BOLERO-1): a phase 3, randomised, double-blind, multicentre trial. Lancet Oncol. 2015 Jul;16(7):816-29. Epub 2015 Jun 16. link to original article PubMed
- Awada A, Colomer R, Inoue K, Bondarenko I, Badwe RA, Demetriou G, Lee SC, Mehta AO, Kim SB, Bachelot T, Goswami C, Deo S, Bose R, Wong A, Xu F, Yao B, Bryce R, Carey LA. Neratinib Plus Paclitaxel vs Trastuzumab Plus Paclitaxel in Previously Untreated Metastatic ERBB2-Positive Breast Cancer: The NEfERT-T Randomized Clinical Trial. JAMA Oncol. 2016 Dec 1;2(12):1557-1564. link to original article contains verified protocol PubMed
TH (Docetaxel)
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TH: Taxotere (Docetaxel), Herceptin (Trastuzumab)
Regimen #1
Study | Evidence | Comparator | Efficacy |
Hurvitz et al. 2013 | Randomized Phase II | T-DM1 | Seems to have inferior PFS |
Gianni et al. 2013 (AVAREL) | Randomized Phase II | BTH | Might have inferior PFS |
Chemotherapy
- Docetaxel (Taxotere) 75 or 100 mg/m2 IV once on day 1
- Dose in Hurvitz et al. 2013 was per investigator's discretion; all patients in AVAREL received 100 mg/m2
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 2
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles, given until progression of disease or unacceptable toxicity
Regimen #2
Study | Evidence | Comparator | Efficacy |
Baselga et al. 2011 (CLEOPATRA) | Phase III | THP | Inferior OS |
This unusual schedule with both medications being given on day 2 of cycle 1 is due to this regimen being the control arm of CLEOPATRA, in which patients in one arm received a placebo instead of pertuzumab on day 1. It is reasonable to assume that in practice, drugs in this regimen will be given on day 1 from the beginning.
Chemotherapy
- Docetaxel (Taxotere) as follows:
- Cycle 1: 75 mg/m2 IV once on day 2
- Cycle 2 onwards: 75 mg/m2 IV once on day 1
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 2
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycle for at least 6 cycles, given until progression of disease or unacceptable toxicity
If it is decided to no longer administer Docetaxel (Taxotere) with this regimen, then patients could continue to receive:
- Trastuzumab (Herceptin) 6 mg/kg IV once on day 1
21-day cycles, given until progression of disease or unacceptable toxicity
Regimen #3
Study | Evidence | Comparator | Efficacy |
Valero et al. 2010 (BCIRG 007) | Phase III | TCH | Seems not superior |
Induction therapy
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV over 90 minutes once on day 1, then 2 mg/kg IV over 30 minutes once per day on days 8 & 15
- Cycles 2 to 8: 2 mg/kg IV over 30 minutes once per day on days 1, 8, 15
Supportive medications
- Dexamethasone (Decadron) 8 mg (or equivalent) PO BID x 6 doses, starting the night before docetaxel
- "Antiemetic premedication was mandatory" (no additional details given).
21-day cycle for 8 cycles
Patients then proceeded to maintenance trastuzumab therapy:
Maintenance trastuzumab
- Trastuzumab (Herceptin) 6 mg/kg IV once every 3 weeks
Given until progression of disease or unacceptable toxicity
Regimen #4
Study | Evidence | Comparator | Efficacy |
Esteva et al. 2002 | Phase II | ||
Burstein et al. 2007 (TRAVIOTA) | Phase III | Trastuzumab & Vinorelbine | Might have inferior TTP |
Esteva et al. 2002 described the day before the start of a cycle as "day 0," which is not the typical convention, so day -1 is being used instead.
Chemotherapy
- Docetaxel (Taxotere) 35 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, given first
- Trastuzumab (Herceptin) given second as follows:
- Cycle 1: 4 mg/kg IV over 90 minutes once on day -1, then 2 mg/kg IV over 30 minutes once per day on days 8 & 15
- Cycle 2 onwards: 2 mg/kg IV over 30 minutes once per day on days 1, 8, 15
Supportive medications
- Dexamethasone (Decadron) 4 mg PO every 12 hours x 3 doses on cycles 1 & 2, starting the night before Docetaxel (Taxotere). Patients who did not have "hypersensitivity reactions and no significant fluid retention during the first 8 weeks" received 4 mg PO BID on day 1 for at least the next two cycles. Patients who "remained free of fluid retention after 8 additional weeks" then received 4 mg PO once on day 1 prior to Docetaxel (Taxotere) in subsequent cycles.
28-day cycles, given until progression of disease or unacceptable toxicity
Regimen #5
Study | Evidence | Comparator | Efficacy |
Marty et al. 2005 (M77001) | Randomized Phase II | Docetaxel | Seems to have superior OS |
Marty et al. 2005 did not exactly specify days of therapy; this is the best guess for what was used based on the description.
Induction therapy
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 2 to 6: 2 mg/kg IV once per day on days 1, 8, 15
Supportive medications
- Corticosteroids prior to docetaxel, "which could include dexamethasone, methylprednisolone, or prednisolone" (no doses/routes/schedule specified).
21-day cycle for 6 cycles, given until progression of disease or unacceptable toxicity
Patients could receive docetaxel beyond six cycles at the discretion of the investigator. Otherwise, patients proceeded to maintenance trastuzumab therapy:
Maintenance trastuzumab
- Trastuzumab (Herceptin) 2 mg/kg IV once per week
Given until progression of disease or unacceptable toxicity
References
- Esteva FJ, Valero V, Booser D, Guerra LT, Murray JL, Pusztai L, Cristofanilli M, Arun B, Esmaeli B, Fritsche HA, Sneige N, Smith TL, Hortobagyi GN. Phase II study of weekly docetaxel and trastuzumab for patients with HER-2-overexpressing metastatic breast cancer. J Clin Oncol. 2002 Apr 1;20(7):1800-8. link to original article contains verified protocol PubMed
- Marty M, Cognetti F, Maraninchi D, Snyder R, Mauriac L, Tubiana-Hulin M, Chan S, Grimes D, Antón A, Lluch A, Kennedy J, O'Byrne K, Conte P, Green M, Ward C, Mayne K, Extra JM. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol. 2005 Jul 1;23(19):4265-74. Epub 2005 May 23. link to original article contains verified protocol PubMed
- Burstein HJ, Keshaviah A, Baron AD, Hart RD, Lambert-Falls R, Marcom PK, Gelman R, Winer EP. Trastuzumab plus vinorelbine or taxane chemotherapy for HER2-overexpressing metastatic breast cancer: the trastuzumab and vinorelbine or taxane study. Cancer. 2007 Sep 1;110(5):965-72. link to original article PubMed
- Valero V, Forbes J, Pegram MD, Pienkowski T, Eiermann W, von Minckwitz G, Roche H, Martin M, Crown J, Mackey JR, Fumoleau P, Rolski J, Mrsic-Krmpotic Z, Jagiello-Gruszfeld A, Riva A, Buyse M, Taupin H, Sauter G, Press MF, Slamon DJ. Multicenter phase III randomized trial comparing docetaxel and trastuzumab with docetaxel, carboplatin, and trastuzumab as first-line chemotherapy for patients with HER2-gene-amplified metastatic breast cancer (BCIRG 007 study): two highly active therapeutic regimens. J Clin Oncol. 2011 Jan 10;29(2):149-56. Epub 2010 Nov 29. link to original article contains verified protocol PubMed
- Baselga J, Cortés J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, Clark E, Benyunes MC, Ross G, Swain SM; CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012 Jan 12;366(2):109-19. Epub 2011 Dec 7. link to original article contains verified protocol PubMed
- Update: Swain SM, Kim SB, Cortés J, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Knott A, Clark E, Ross G, Benyunes MC, Baselga J. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2013 May;14(6):461-71. Epub 2013 Apr 18. link to original article link to PMC article contains verified protocol PubMed
- Update: Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S, Clark E, Ross G, Benyunes MC, Cortés J; CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015 Feb 19;372(8):724-34. link to original article PubMed
- Hurvitz SA, Dirix L, Kocsis J, Bianchi GV, Lu J, Vinholes J, Guardino E, Song C, Tong B, Ng V, Chu YW, Perez EA. Phase II Randomized Study of Trastuzumab Emtansine Versus Trastuzumab Plus Docetaxel in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer. J Clin Oncol. 2013 Mar 20;31(9):1157-63. Epub 2013 Feb 4. Erratum in: J Clin Oncol. 2013 Aug 10;31(23):2977. link to original article contains verified protocol PubMed
- Gianni L, Romieu GH, Lichinitser M, Serrano SV, Mansutti M, Pivot X, Mariani P, Andre F, Chan A, Lipatov O, Chan S, Wardley A, Greil R, Moore N, Prot S, Pallaud C, Semiglazov V. AVEREL: a randomized phase III Trial evaluating bevacizumab in combination with docetaxel and trastuzumab as first-line therapy for HER2-positive locally recurrent/metastatic breast cancer. J Clin Oncol. 2013 May 10;31(14):1719-25. Epub 2013 Apr 8. link to original article contains verified protocol PubMed
THP (Docetaxel)
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THP: Taxotere (Docetaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen
Study | Evidence | Comparator | Efficacy |
Baselga et al. 2011 (CLEOPATRA) | Phase III | Docetaxel & Trastuzumab | Superior OS |
Chemotherapy
- Docetaxel (Taxotere) as follows:
- Cycle 1: 75 mg/m2 IV once on day 2
- Cycle 2 onwards: 75 mg/m2 IV once on day 1
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 2
- Cycle 2 onwards: 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycle 2 onwards: 420 mg IV once on day 1
21-day cycle for at least 6 cycles, given until progression of disease or unacceptable toxicity
If it is decided to no longer administer Docetaxel (Taxotere) with this regimen, then patients could continue to receive:
- Trastuzumab (Herceptin) 6 mg/kg IV once on day 1
- Pertuzumab (Perjeta) 420 mg IV once on day 1
21-day cycles, given until progression of disease or unacceptable toxicity
References
- Baselga J, Cortés J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, Clark E, Benyunes MC, Ross G, Swain SM; CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012 Jan 12;366(2):109-19. Epub 2011 Dec 7. link to original article contains verified protocol PubMed
- Update: Swain SM, Kim SB, Cortés J, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Knott A, Clark E, Ross G, Benyunes MC, Baselga J. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2013 May;14(6):461-71. Epub 2013 Apr 18. link to original article link to PMC article contains verified protocol PubMed
- Update: Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S, Clark E, Ross G, Benyunes MC, Cortés J; CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015 Feb 19;372(8):724-34. link to original article PubMed
XH
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XH: Xeloda, Herceptin
Regimen #1
Study | Evidence | Comparator | Efficacy |
von Minckwitz et al. 2009 (GBG 26/BIG 3-05) | Phase III | Capecitabine | Seems to have superior TTP |
Chemotherapy
- Capecitabine (Xeloda) 1250 mg/m2 PO BID days 1 to 14
- Trastuzumab (Herceptin) 6 mg/kg IV once on day 1
21-day cycles
Regimen #2
Study | Evidence |
Bartsch et al. 2007 | Phase II |
Chemotherapy
- Capecitabine (Xeloda) 1000 to 1250 mg/m2 PO BID days 1 to 14
- EITHER Trastuzumab (Herceptin) 4 mg/kg IV once on cycle 1 day 1, then 2 mg/kg IV once per day on days 8 & 15 of cycle 1; then on subsequent cycles, Trastuzumab (Herceptin) is 2 mg/kg IV once per day on days 1, 8, 15
- OR Trastuzumab (Herceptin) 8 mg/kg IV once on cycle 1 day 1, then on subsequent cycles Trastuzumab (Herceptin) is 6 mg/kg IV once on day 1
21-day cycles
References
- Bartsch R, Wenzel C, Altorjai G, Pluschnig U, Rudas M, Mader RM, Gnant M, Zielinski CC, Steger GG. Capecitabine and trastuzumab in heavily pretreated metastatic breast cancer. J Clin Oncol. 2007 Sep 1;25(25):3853-8. Epub 2007 Aug 6. link to original article PubMed
- von Minckwitz G, du Bois A, Schmidt M, Maass N, Cufer T, de Jongh FE, Maartense E, Zielinski C, Kaufmann M, Bauer W, Baumann KH, Clemens MR, Duerr R, Uleer C, Andersson M, Stein RC, Nekljudova V, Loibl S. Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: a german breast group 26/breast international group 03-05 study. J Clin Oncol. 2009 Apr 20;27(12):1999-2006. Epub 2009 Mar 16. link to original article PubMed
- Update: von Minckwitz G, Schwedler K, Schmidt M, Barinoff J, Mundhenke C, Cufer T, Maartense E, de Jongh FE, Baumann KH, Bischoff J, Harbeck N, Lück HJ, Maass N, Zielinski C, Andersson M, Stein RC, Nekljudova V, Loibl S; GBG 26/BIG 03-05 study group and participating investigators. Trastuzumab beyond progression: overall survival analysis of the GBG 26/BIG 3-05 phase III study in HER2-positive breast cancer. Eur J Cancer. 2011 Oct;47(15):2273-81. Epub 2011 Jul 7. link to original article PubMed
Trastuzumab (Herceptin) & other single agent chemotherapy
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Regimen
- EITHER Trastuzumab (Herceptin) 4 mg/kg IV once on cycle 1 day 1, then 2 mg/kg IV once per day on days 8 & 15 of cycle 1; then on subsequent cycles, Trastuzumab (Herceptin) is 2 mg/kg IV once per day on days 1, 8, 15
- OR Trastuzumab (Herceptin) 8 mg/kg IV once on cycle 1 day 1, then on subsequent cycles Trastuzumab (Herceptin) is 6 mg/kg IV once on day 1
- A single agent chemotherapy regimen described above
21-day cycles
References
See single agent chemotherapy regimens
Trastuzumab & Vinorelbine
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Regimen
Study | Evidence | Comparator | Efficacy |
Burstein et al. 2007 (TRAVIOTA) | Phase III | TH (Docetaxel) TH (Paclitaxel) |
Might have superior TTP |
André et al. 2014 (BOLERO-3) | Phase III | Everolimus, Trastuzumab, Vinorelbine | Inferior PFS |
Harbeck et al. 2016 (LUX-Breast 1) | Phase III | Afatinib & Vinorelbine | Seems not superior |
Chemotherapy
- Vinorelbine (Navelbine) 25 mg/m2 IV once per week
- Trastuzumab (Herceptin) 4 mg/kg IV once on day 1, then 2 mg/kg IV once per week
Given until progression, intolerance, or request to discontinue therapy
References
- Burstein HJ, Keshaviah A, Baron AD, Hart RD, Lambert-Falls R, Marcom PK, Gelman R, Winer EP. Trastuzumab plus vinorelbine or taxane chemotherapy for HER2-overexpressing metastatic breast cancer: the trastuzumab and vinorelbine or taxane study. Cancer. 2007 Sep 1;110(5):965-72. link to original article PubMed
- André F, O'Regan R, Ozguroglu M, Toi M, Xu B, Jerusalem G, Masuda N, Wilks S, Arena F, Isaacs C, Yap YS, Papai Z, Lang I, Armstrong A, Lerzo G, White M, Shen K, Litton J, Chen D, Zhang Y, Ali S, Taran T, Gianni L. Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2014 May;15(6):580-91. Epub 2014 Apr 14. link to original article PubMed
- Harbeck N, Huang CS, Hurvitz S, Yeh DC, Shao Z, Im SA, Jung KH, Shen K, Ro J, Jassem J, Zhang Q, Im YH, Wojtukiewicz M, Sun Q, Chen SC, Goeldner RG, Uttenreuther-Fischer M, Xu B, Piccart-Gebhart M; LUX-Breast 1 study group. Afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one previous trastuzumab treatment (LUX-Breast 1): an open-label, randomised, phase 3 trial. Lancet Oncol. 2016 Mar;17(3):357-66. link to SD article contains verified protocol PubMed
Additional resources
- Gail model Breast Cancer Risk Assessment Tool
- Breast cancer BRCA1/BRCA2 genetic testing
- Adjuvant! Online (requires login)
- My Cancer Genome