Breast cancer, HER2-positive
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Section editor transclusions Note: these are biomarker-specific regimens, please see the main breast cancer page for other regimens.
123 regimens on this page
205 variants on this page
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Guidelines
ASCO
- 2016: 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
- 2015: Use of biomarkers to guide decisions on systemic therapy for women with metastatic breast cancer: American Society of Clinical Oncology Clinical practice guideline
- 2014: Systemic therapy for patients with advanced human epidermal growth factor receptor 2-positive breast cancer: American Society of Clinical Oncology clinical practice guideline PubMed
ESMO
- 2017: 3rd ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3). PubMed
- 2015: Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. PubMed
NCCN
Neoadjuvant chemotherapy
FEC & H
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FEC & H: Fluorouracil, Epirubicin, Cyclophosphamide, Herceptin (Trastuzumab)
Regimen #1, IV trastuzumab
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Ismael et al. 2012 (HannaH) | Randomized | See link | See link |
Preceding treatment
- TH (IV) x 4
Chemotherapy
- 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
- Trastuzumab (Herceptin) 6 mg/kg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- Surgery
Regimen #2, SC trastuzumab
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Ismael et al. 2012 (HannaH) | Randomized | See link | See link |
Preceding treatment
- TH (SC) x 4
Chemotherapy
- 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
- Trastuzumab (Herceptin) 600 mg SC once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- Surgery
Regimen #3
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Buzdar et al. 2005 | Randomized | See link | See link |
Preceding treatment
- TH x 4
Chemotherapy
- 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
Subsequent treatment
- 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
- 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 verified protocol PubMed
Lapatinib monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Baselga et al. 2012 (NeoALTTO) | Phase III | 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.
Chemotherapy
- Lapatinib (Tykerb) 1500 mg PO once per day
6-week course
Subsequent treatment
- TL (Taxol) x 12 wk, then surgery
References
- 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 verified protocol PubMed
- 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
Lapatinib & Trastuzumab
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Baselga et al. 2012 (NeoALTTO) | Phase III | 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.
Chemotherapy
- 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 week
6-week course
Subsequent treatment
- THL (Taxol) x 12 wk, then surgery
References
- 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 verified protocol PubMed
- 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
Neratinib & Paclitaxel
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Park et al. 2016 (I-SPY 2) | Adaptively Randomized Phase II | TH | Seems to have superior pCR rate |
Chemotherapy
- Neratinib (Nerlynx) 240 mg PO once per day
- Paclitaxel (Taxol) 80 mg/m2 IV once per week
Supportive medications
- Loperamide (Imodium) 4 mg PO on day 1 of Neratinib (Nerlynx), 2 mg PO 8 hours later, and then 2 mg PO BID for two weeks, then decreased per patient choice
12-week course
Subsequent treatment
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 link to PMC article PubMed
TCHP (Taxotere)
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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, then THP | Not reported |
FEC, then THP | Not reported | ||
Hurvitz et al. 2017 (KRISTINE) | Phase III | Pertuzumab & T-DM1 | Seems to have superior pCR rate |
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: 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
Subsequent treatment
- TRYPHAENA: Surgery, then adjuvant trastuzumab; further adjuvant treatment (radiotherapy, chemotherapy, hormonal treatment) according to local guidelines
- KRISTINE: Surgery
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. Epub 2013 May 22. link to original article contains verified protocol PubMed
- 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 protocol PubMed
TH (Taxol)
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TH: Taxol (Paclitaxel) & Herceptin (Trastuzumab)
T-T: Taxol (Paclitaxel) & Trastuzumab
Regimen #1, weekly paclitaxel x 12
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Baselga et al. 2012 (NeoALTTO) | Phase III | See link | See link |
Buzdar et al. 2013 (ACOSOG Z1041) | Phase III | See link | See link |
Park et al. 2016 (I-SPY 2) | Adaptively Randomized Phase II | Neratinib & Paclitaxel | Seems to have inferior pCR rate |
Note: 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
- ACOSOG Z1041: FEC x 4
Chemotherapy
- 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
Subsequent treatment
- NeoALTTO: Surgery, then adjuvant FEC x 3
- ACOSOG Z1041: Surgery
- I-SPY 2: AC or ddAC, then surgery
Regimen #2, paclitaxel 3 out of 4 weeks
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Robidoux et al. 2013 (NSABP B-41) | Phase III | THL | Might have inferior pCR rate |
TL | Seems not superior |
Preceding treatment
- AC x 4
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
- 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 trastuzumab for a total of 52 weeks of therapy.
Regimen #3, CI paclitaxel
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Buzdar et al. 2005 | Randomized | See link | See link |
Chemotherapy
- 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
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 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
- 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 verified protocol PubMed
- 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
- 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
- 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 investigators. 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 verified protocol PubMed
- 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 link to PMC article PubMed
TH (Taxotere)
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TH: Taxotere (Docetaxel) & Herceptin (Trastuzumab)
Regimen #1, IV trastuzumab
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Ismael et al. 2012 (HannaH) | Randomized | See link | See link |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 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
21-day cycle for 4 cycles
Subsequent treatment
Regimen #2, SC trastuzumab
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Ismael et al. 2012 (HannaH) | Randomized | See link | See link |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- Trastuzumab (Herceptin) 600 mg SC once on day 1
21-day cycle for 4 cycles
Subsequent treatment
Regimen #3
Study | Evidence | Efficacy |
---|---|---|
Van Pelt et al. 2003 | Phase II | OCR: 77% |
Chemotherapy
- Docetaxel (Taxotere) as follows:
- Cycle 0: no treatment
- Cycles 1 to 4: 100 mg/m2 IV once on day 1
- Trastuzumab (Herceptin) 4 mg/kg IV once on day 1, then 2 mg/kg IV once per week
21-day cycle for 5 cycles
Subsequent treatment
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. contains protocol PubMed
- 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 verified protocol PubMed
THL (Taxol)
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THL: Taxol (Paclitaxel), Herceptin (Trastuzumab), Lapatinib
Regimen #1, weekly paclitaxel x 12
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Baselga et al. 2012 (NeoALTTO) | Phase III | See link | See link |
Preceding treatment
- Lapatinib & Trastuzumab x 6 wk
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per week
- Trastuzumab (Herceptin) 2 mg/kg IV once per week
- Lapatinib (Tykerb) 1000 mg PO once per day
12-week course
Subsequent treatment
- Surgery, then adjuvant FEC x 3
Regimen #2, paclitaxel 3 out of 4 weeks
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Robidoux et al. 2013 (NSABP B-41) | Phase III | TH | Might have superior pCR rate |
TL | Might have superior pCR rate |
Preceding treatment
- AC x 4
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
- 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, then adjuvant trastuzumab for a total of 52 weeks of therapy
References
- 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 verified protocol PubMed
- 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
- 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
THP (Taxotere)
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THP: Taxotere (Docetaxel), Herceptin (Trastuzumab), Pertuzumab
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 to 100 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- Surgery, then 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
TL (Taxol)
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TL: Taxol (Paclitaxel) & Lapatinib
Regimen #1, weekly paclitaxel x 12
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Baselga et al. 2012 (NeoALTTO) | Phase III | See link | See link |
Preceding treatment
- Lapatinib x 6 wk
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per week
- Lapatinib (Tykerb) 1500 mg PO once per day
12-week course
Subsequent treatment
- Surgery, then adjuvant FEC x 3
Regimen #2, paclitaxel 3 out of 4 weeks
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Robidoux et al. 2013 (NSABP B-41) | Phase III | TH | Seems not superior |
THL | Might have inferior pCR rate |
Preceding treatment
- AC x 4
Chemotherapy
- 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
Subsequent treatment
- Surgery, then adjuvant trastuzumab for a total of 52 weeks of therapy
References
- 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 verified protocol PubMed
- 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
- 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
T-DM1
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T-DM1: Trastuzumab-DM1 (ado-Trastuzumab emtansine)
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Harbeck et al. 2017 (WGSG ADAPT) | Randomized Phase II | T-DM1 & ET | Not reported |
Trastuzumab & ET | Superior pCR rate |
Chemotherapy
- Ado-trastuzumab emtansine (Kadcyla) 3.6 mg/kg IV once on day 1
21-day cycle for 4 cycles
Surgery was performed within 3 weeks of the end of therapy. Adjuvant therapy consisted of Breast_cacner#EC_2, then TH (Taxol), unless the patient had pCR in which case adjuvant therapy was optional.
References
- Harbeck N, Gluz O, Christgen M, Kates RE, Braun M, Küemmel S, Schumacher C, Potenberg J, Kraemer S, Kleine-Tebbe A, Augustin D, Aktas B, Forstbauer H, Tio J, von Schumann R, Liedtke C, Grischke EM, Schumacher J, Wuerstlein R, Kreipe HH, Nitz UA. De-escalation strategies in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC): Final analysis of the West German Study Group Adjuvant Dynamic marker-Adjusted Personalized Therapy trial optimizing risk assessment and therapy response prediction in early BC HER2- and hormone receptor-positive phase II randomized trial-efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET. J Clin Oncol. 2017 Sep 10;35(26):3046-3054. Epub 2017 Jul 6. link to original article contains verified protocol PubMed
T-DM1 & ET
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T-DM1 & ET: Trastuzumab-DM1 (ado-Trastuzumab emtansine) & Endocrine Therapy
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Harbeck et al. 2017 (WGSG ADAPT) | Randomized Phase II | T-DM1 | Not reported |
Trastuzumab & ET | Superior pCR rate |
Chemotherapy
- Ado-trastuzumab emtansine (Kadcyla) 3.6 mg/kg IV once on day 1
- Endocrine therapy as follows:
- Premenopausal women: Tamoxifen (Nolvadex) recommended
- GnRH analogs were also allowed
- Postmenopausal women: Aromatase inhibitor recommended
21-day cycle for 4 cycles
Surgery was performed within 3 weeks of the end of therapy. Adjuvant therapy consisted of Breast_cacner#EC_2, then TH (Taxol), unless the patient had pCR in which case adjuvant therapy was optional.
References
- Harbeck N, Gluz O, Christgen M, Kates RE, Braun M, Küemmel S, Schumacher C, Potenberg J, Kraemer S, Kleine-Tebbe A, Augustin D, Aktas B, Forstbauer H, Tio J, von Schumann R, Liedtke C, Grischke EM, Schumacher J, Wuerstlein R, Kreipe HH, Nitz UA. De-escalation strategies in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC): Final analysis of the West German Study Group Adjuvant Dynamic marker-Adjusted Personalized Therapy trial optimizing risk assessment and therapy response prediction in early BC HER2- and hormone receptor-positive phase II randomized trial-efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET. J Clin Oncol. 2017 Sep 10;35(26):3046-3054. Epub 2017 Jul 6. link to original article contains verified protocol PubMed
Trastuzumab monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Baselga et al. 2012 (NeoALTTO) | Phase III | 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.
Chemotherapy
- Trastuzumab (Herceptin) 4 mg/kg IV once on day 1, then 2 mg/kg IV once per week
6-week course
Subsequent treatment
- TH (Taxol) x 12 wk, then surgery
References
- 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 verified protocol PubMed
- 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
Trastuzumab & ET
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ET: Endocrine Therapy
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Harbeck et al. 2017 (WGSG ADAPT) | Randomized Phase II | T-DM1 T-DM1 & ET |
Inferior pCR rate |
Chemotherapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 4: 6 mg/kg IV once on day 1
- Endocrine therapy as follows:
- Premenopausal women: Tamoxifen (Nolvadex) recommended
- GnRH analogs were also allowed
- Postmenopausal women: Aromatase inhibitor recommended
21-day cycle for 4 cycles
Surgery was performed within 3 weeks of the end of therapy. Adjuvant therapy consisted of Breast_cacner#EC_2, then TH (Taxol), unless the patient had pCR in which case adjuvant therapy was optional.
References
- Harbeck N, Gluz O, Christgen M, Kates RE, Braun M, Küemmel S, Schumacher C, Potenberg J, Kraemer S, Kleine-Tebbe A, Augustin D, Aktas B, Forstbauer H, Tio J, von Schumann R, Liedtke C, Grischke EM, Schumacher J, Wuerstlein R, Kreipe HH, Nitz UA. De-escalation strategies in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC): Final analysis of the West German Study Group Adjuvant Dynamic marker-Adjusted Personalized Therapy trial optimizing risk assessment and therapy response prediction in early BC HER2- and hormone receptor-positive phase II randomized trial-efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET. J Clin Oncol. 2017 Sep 10;35(26):3046-3054. Epub 2017 Jul 6. link to original article contains verified protocol PubMed
Adjuvant chemotherapy
ddTH (Taxol)
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ddTH: dose-dense Taxol (Paclitaxel) & Herceptin (Trastuzumab)
Regimen
Study | Evidence |
---|---|
Dang et al. 2008 | Phase II |
Preceding treatment
- ddAC x 4
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
- Trastuzumab (Herceptin) as follows:
- Week 1: 4 mg/kg IV once with first dose of paclitaxel
- Weeks 2 to 8: 2 mg/kg IV once per week
- Weeks 9 to 52: 6 mg/kg IV once every 3 weeks
Supportive medications
- Pegfilgrastim (Neulasta) SC once on day 2 of cycles 1 to 4
14-day cycle for 4 cycles (paclitaxel), 52 weeks of trastuzumab
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 verified protocol PubMed
FEC & H
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Regimen
Study | Evidence |
---|---|
Gianni et al. 2011 (NeoSphere) | Non-randomized portion of RCT |
Preceding treatment
- Neoadjuvant docetaxel & pertuzumab versus neoadjuvant docetaxel, pertuzumab, trastuzumab versus neoadjuvant pertuzumab & trastuzumab versus neoadjvuant TH, and 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
- Trastuzumab (Herceptin) 6 mg/kg IV once on day 1
21-day cycle for 18 cycles
Subsequent treatment
- Radiation therapy and/or hormone therapy for ER positive patients is given "per local guidelines"
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
Lapatinib monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Baselga et al. 2012 (NeoALTTO) | Phase III | 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.
Preceding treatment
- adjuvant FEC x 3
Chemotherapy
- Lapatinib (Tykerb) 1500 mg PO once per day
34-week course
References
- 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 verified protocol PubMed
- 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
Lapatinib & Trastuzumab
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Baselga et al. 2012 (NeoALTTO) | Phase III | 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.
Preceding treatment
- adjuvant FEC x 3
Chemotherapy
- 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
- 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 verified protocol PubMed
- 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
Neratinib monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Chan et al. 2016 (ExteNET) | Phase III | Placebo | Superior invasive DFS |
Preceding treatment
- Surgery and trastuzumab-containing chemotherapy (neoadjuvant or adjuvant)
Chemotherapy
- Neratinib (Nerlynx) 240 mg PO once per day
12-month course
References
- Chan A, Delaloge S, Holmes FA, Moy B, Iwata H, Harvey VJ, Robert NJ, Silovski T, Gokmen E, von Minckwitz G, Ejlertsen B, Chia SK, Mansi J, Barrios CH, Gnant M, Buyse M, Gore I, Smith J 2nd, Harker G, Masuda N, Petrakova K, Zotano AG, Iannotti N, Rodriguez G, Tassone P, Wong A, Bryce R, Ye Y, Yao B, Martin M; ExteNET Study Group. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2016 Mar;17(3):367-77. Epub 2016 Feb 10. link to original article contains verified protocol PubMed
- Update: Martin M, Holmes FA, Ejlertsen B, Delaloge S, Moy B, Iwata H, von Minckwitz G, Chia SKL, Mansi J, Barrios CH, Gnant M, Tomašević Z, Denduluri N, Šeparović R, Gokmen E, Bashford A, Ruiz Borrego M, Kim SB, Jakobsen EH, Ciceniene A, Inoue K, Overkamp F, Heijns JB, Armstrong AC, Link JS, Joy AA, Bryce R, Wong A, Moran S, Yao B, Xu F, Auerbach A, Buyse M, Chan A; ExteNET Study Group. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1688-1700. Epub 2017 Nov 13. link to original article PubMed
Placebo
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Chan et al. 2016 (ExteNET) | Phase III | Neratinib | Inferior invasive DFS |
No further treatment after surgery and trastuzumab-containing chemotherapy (neoadjuvant or adjuvant).
References
- Chan A, Delaloge S, Holmes FA, Moy B, Iwata H, Harvey VJ, Robert NJ, Silovski T, Gokmen E, von Minckwitz G, Ejlertsen B, Chia SK, Mansi J, Barrios CH, Gnant M, Buyse M, Gore I, Smith J 2nd, Harker G, Masuda N, Petrakova K, Zotano AG, Iannotti N, Rodriguez G, Tassone P, Wong A, Bryce R, Ye Y, Yao B, Martin M; ExteNET Study Group. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2016 Mar;17(3):367-77. Epub 2016 Feb 10. link to original article contains verified protocol PubMed
- Update: Martin M, Holmes FA, Ejlertsen B, Delaloge S, Moy B, Iwata H, von Minckwitz G, Chia SKL, Mansi J, Barrios CH, Gnant M, Tomašević Z, Denduluri N, Šeparović R, Gokmen E, Bashford A, Ruiz Borrego M, Kim SB, Jakobsen EH, Ciceniene A, Inoue K, Overkamp F, Heijns JB, Armstrong AC, Link JS, Joy AA, Bryce R, Wong A, Moran S, Yao B, Xu F, Auerbach A, Buyse M, Chan A; ExteNET Study Group. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1688-1700. Epub 2017 Nov 13. link to original article PubMed
TCH (Taxotere, Carboplatin)
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TCH: Taxotere (Docetaxel), Carboplatin, Herceptin (Trastuzumab)
Regimen #1
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | Phase III | TCHP | Seems to have inferior invasive DFS |
Preceding treatment
- Surgery
Chemotherapy
- Docetaxel (Taxotere) as follows:
- Cycles 1 to 6: 75 mg/m2 IV once on day 1
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6: AUC 6 (maximum dose: 900 mg) IV once on day 1
- 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 cycle for up to 1 year of therapy (18 doses of trastuzumab)
Regimen #2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Slamon et al. 2011 (BCIRG 006) | Phase III | AC, then T | Seems to have superior OS |
AC, then TH | Seems not superior |
Chemotherapy
- Docetaxel (Taxotere) as follows:
- Cycles 1 to 6: 75 mg/m2 IV once on day 1
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6: AUC 6 IV once on day 1
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8 & 15
- Cycles 2 to 6: 2 mg/kg IV once per day on days 1, 8, 15
- Cycles 7 to 18: 6 mg/kg IV once on day 1
21-day cycle for 18 cycles
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 link to PMC article PubMed
- 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 verified protocol in supplementary protocol link to PMC article PubMed
TCH (Taxotere, Cyclophosphamide)
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TCH: Taxotere, Cyclophosphamide, Herceptin
Regimen
Study | Evidence |
---|---|
Jones et al. 2013 | Phase II |
Preceding treatment
- Surgery, within 84 days
Chemotherapy
- Docetaxel (Taxotere) as follows:
- Cycles 1 to 4: 75 mg/m2 IV over 60 minutes once on day 1
- Cyclophosphamide (Cytoxan) as follows:
- Cycles 1 to 4: 600 mg/m2 IV over 15 to 30 minutes once on day 1
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 4 mg/kg IV over 90 minutes once on day 1, then 2 mg/kg IV over 30 to 60 minutes once per day on days 8 & 15
- Cycles 2 to 4: 2 mg/kg IV over 30 to 60 minutes once per day on days 1, 8, 15
- Cycles 6 to 18: 6 mg/kg IV once on day 1
Supportive medications
- Use of Filgrastim (Neupogen) or Pegfilgrastim (Neulasta) was allowed.
- Prophylactic antibiotics were not recommended.
21-day cycle for 18 cycles
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
TCHP (Taxotere)
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TCHP: Taxotere (Docetaxel), Carboplatin, Herceptin (Trastuzumab), Pertuzumab
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | Phase III | TCH | Seems to have superior invasive DFS |
Preceding treatment
- Surgery
Chemotherapy
- Docetaxel (Taxotere) as follows:
- Cycles 1 to 6: 75 mg/m2 IV once on day 1
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6: AUC 6 (maximum dose: 900 mg) IV once on day 1
- 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
- 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 up to 1 year of therapy (18 doses of trastuzumab & pertuzumab)
References
- von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains verified protocol in supplementary protocol link to PMC article PubMed
TH (Taxol)
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TH: Taxol (Paclitaxel) & Herceptin (Trastuzumab)
PH: Paclitaxel & Herceptin (Trastuzumab)
Regimen #1, weekly paclitaxel, q3wk trastuzumab
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | Phase III | THP (Taxol) | Seems to have inferior invasive 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
- Paclitaxel (Taxol) as follows:
- Weeks 1 to 12: 80 mg/m2 IV once per week
- Trastuzumab (Herceptin) as follows:
- Week 1: 8 mg/kg IV once on day 1
- Week 4 onwards: 6 mg/kg IV once every 3 weeks
Up to 1 year of therapy (18 doses of trastuzumab)
Regimen #2, weekly paclitaxel, weekly trastuzumab
Study | Evidence |
---|---|
Tolaney et al. 2015 (APT) | Phase II |
Preceding treatment
- Surgery
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per week on weeks 1 to 12
- Trastuzumab (Herceptin) as follows:
- Week 1: 4 mg/kg IV once on day 1 with the first dose of paclitaxel
- Weeks 2 to 52: 2 mg/kg IV once per week
12 weeks of paclitaxel, 52 weeks of trastuzumab
Regimen #3, weekly paclitaxel, weekly then q3wk trastuzumab
Study | Evidence |
---|---|
Tolaney et al. 2015 (APT) | Phase II |
Preceding treatment
- Surgery
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per week on weeks 1 to 12
- Trastuzumab (Herceptin) as follows:
- Week 1: 4 mg/kg IV once on day 1 with the first dose of paclitaxel
- Weeks 2 to 12: 2 mg/kg IV once per week
- Weeks 13 to 52: 6 mg/kg IV once every 3 weeks
12 weeks of paclitaxel, 52 weeks of trastuzumab
Regimen #4, q3wk paclitaxel, weekly trastuzumab
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Romond et al. 2005 (NSABP B-31) | Phase III | T (Taxol) | Superior OS | Might have superior DASI score |
Romond et al. 2005 (NCCTG N9831) | Phase III | 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.
Preceding treatment
- AC x 4
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once per week on weeks 1, 4, 7, 10
- Trastuzumab (Herceptin) as follows:
- Week 1: 4 mg/kg IV once on day 1
- Weeks 2 to 52: 2 mg/kg IV once per week
4 cycles of paclitaxel, 52 weeks of trastuzumab
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, 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
- 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
- Update and 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
- Shulman LN, Cirrincione CT, Berry DA, Becker HP, Perez EA, O'Regan R, Martino S, Atkins JN, Mayer E, Schneider CJ, Kimmick G, Norton L, Muss H, Winer EP, Hudis C. Six Cycles of Doxorubicin and Cyclophosphamide or Paclitaxel Are Not Superior to Four Cycles As Adjuvant Chemotherapy for Breast Cancer in Women With Zero to Three Positive Axillary Nodes: Cancer and Leukemia Group B 40101. J Clin Oncol. 2012 Nov 20;30(33):4071-6. Epub 2012 Jul 23. link to original article does not contain protocol link to study protocol PDF link to PMC article 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 link to PMC article PubMed
- 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 verified protocol in supplementary protocol link to PMC article PubMed
TH (Taxotere)
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TH: Taxotere (Docetaxel) & Herceptin (Trastuzumab)
Regimen #1
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | Phase III | THP (Taxotere) | Seems to have inferior invasive 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) as follows:
- Cycles 1 to 3: 100 mg/m2 IV once on day 1
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycle for up to 1 year of therapy (18 doses of trastuzumab)
Regimen #2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | THP (Taxotere) | Seems to have inferior invasive 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) as follows:
- Cycle 1: 75 mg/m2 IV once on day 1
- Cycles 2 & 3: 100 mg/m2 IV once on day 1
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycle for up to 1 year of therapy (18 doses of trastuzumab)
Regimen #3
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | Phase III | THP (Taxotere) | Seems to have inferior invasive 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) as follows:
- Cycles 1 to 4: 75 mg/m2 IV once on day 1
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycle for up to 1 year of therapy (18 doses of trastuzumab)
Regimen #4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Slamon et al. 2011 (BCIRG 006) | Phase III | 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.
Preceding treatment
- AC x 4
Chemotherapy
- Docetaxel (Taxotere) as follows:
- Cycles 1 to 4: 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
- Cycles 5 to 18: 6 mg/kg IV once on day 1
21-day cycle for 18 cycles
Regimen #5, 9 wk of trastuzumab
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Joensuu et al. 2006 (FinHer) | Phase III | T V |
Seems not superior |
VH | Not reported |
Preceding treatment
- Surgery
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV over 60 minutes 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
Subsequent treatment
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
- Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J; Breast Cancer International Research Group. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011 Oct 6;365(14):1273-83. link to original article link to PMC article contains verified protocol PubMed
- 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 verified protocol in supplementary protocol link to PMC article PubMed
THP (Taxol)
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THP: Taxol (Paclitaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | Phase III | TH (Taxol) | Seems to have superior invasive 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
- Paclitaxel (Taxol) as follows:
- Weeks 1 to 12: 80 mg/m2 IV once per week
- 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
- 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 up to 1 year of therapy (18 doses of trastuzumab)
References
- von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains verified protocol in supplementary protocol link to PMC article PubMed
THP (Taxotere)
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THP: Taxotere (Docetaxel), Herceptin (Trastuzumab), Pertuzumab
Regimen #1
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | Phase III | TH (Taxotere) | Seems to have superior invasive 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) as follows:
- Cycles 1 to 3: 100 mg/m2 IV once on day 1
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
- 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 up to 1 year of therapy (18 doses of trastuzumab)
Regimen #2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | Phase III | TH (Taxotere) | Seems to have superior invasive 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) as follows:
- Cycle 1: 75 mg/m2 IV once on day 1
- Cycles 2 & 3: 100 mg/m2 IV once on day 1
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
- 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 up to 1 year of therapy (18 doses of trastuzumab)
Regimen #3
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2017 (APHINITY) | Phase III | TH (Taxotere) | Seems to have superior invasive 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) as follows:
- Cycles 1 to 4: 75 mg/m2 IV once on day 1
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
- 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 up to 1 year of therapy (18 doses of trastuzumab)
References
- von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains verified protocol in supplementary protocol link to PMC article PubMed
VH
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VH: Vinorelbine & Herceptin (Trastuzumab)
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Joensuu et al. 2006 (FinHer) | Phase III | T V |
Seems not superior |
TH (Taxotere) | Not reported |
Chemotherapy
- 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
Subsequent treatment
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 monotherapy
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Regimen #1, 34-week course, q3wk
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Baselga et al. 2012 (NeoALTTO) | Phase III | 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.
Preceding treatment
- adjuvant FEC x 3
Chemotherapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV over 90 minutes once on day 1
- Cycles 2 to 12: 6 mg/kg IV over 30 minutes once on day 1
21-day cycle for 12 cycles (34-week course)
Regimen #2, 1-year course, q3wk
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Piccart-Gebhart et al. 2005 (HERA) | Phase III (E) | No trastuzumab after (neo-)adjuvant chemotherapy | Superior OS |
Trastuzumab x 2 y | Seems not superior | ||
Pivot et al. 2013 (PIVOT) | Phase III (C) | Trastuzumab x 6 mo | Inconclusive whether non-inferior |
Participants had already received at least four courses of an approved (neo-)adjuvant chemotherapy regimen.
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
21-day cycles for 1 year
Regimen #3, 2-year course
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Piccart-Gebhart et al. 2005 (HERA) | Phase III (E) | No trastuzumab after (neo-)adjuvant chemotherapy | Not reported |
Trastuzumab x 1 y | Seems not superior |
Participants had already received at least four courses of an approved (neo-)adjuvant chemotherapy regimen.
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
21-day cycles for 2 years
Regimen #4, 1-year course, weekly
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Van Pelt et al. 2003 | Phase II | ||
Romond et al. 2005 (NCCTG N9831) | Phase III | 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. Van Pelt et al. 2003 does not describe a loading dose (in the abstract).
Preceding treatment
Chemotherapy
- Trastuzumab (Herceptin) 4 mg/kg IV loading dose, then 2 mg/kg IV once per week
52-week course
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. PubMed
- 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 original article PubMed
- Update: Cameron D, Piccart-Gebhart MJ, Gelber RD, Procter M, Goldhirsch A, de Azambuja E, Castro G Jr, Untch M, Smith I, Gianni L, Baselga J, Al-Sakaff N, Lauer S, McFadden E, Leyland-Jones B, Bell R, Dowsett M, Jackisch C; Herceptin Adjuvant (HERA) Trial Study Team. 11 years' follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017 Mar 25;389(10075):1195-1205. Epub 2017 Feb 17. link to original article link to PMC article PubMed
- 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, 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
- 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
- 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 verified protocol PubMed
- 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
- 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 link to PMC article 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
- 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. Epub 2013 May 22.2013 Sep;24(9):2278-84. Epub 2013 May 22. link to original article contains verified protocol PubMed
- Pivot X, Romieu G, Debled M, Pierga JY, Kerbrat P, Bachelot T, Lortholary A, Espié M, Fumoleau P, Serin D, Jacquin JP, Jouannaud C, Rios M, Abadie-Lacourtoisie S, Tubiana-Mathieu N, Cany L, Catala S, Khayat D, Pauporté I, Kramar A; PHARE trial investigators. 6 months versus 12 months of adjuvant trastuzumab for patients with HER2-positive early breast cancer (PHARE): a randomised phase 3 trial. Lancet Oncol. 2013 Jul;14(8):741-8. Epub 2013 Jun 11. link to original article PubMed
- 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 PubMed
Metastatic or unresectable disease, first-line
Note: some patients in these trials were pre-treated with non-HER2-targeted therapies.
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 monotherapy
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Example orders
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Hurvitz et al. 2013 | Randomized Phase II | TH | Seems to have superior PFS |
Perez et al. 2016 (MARIANNE) | Phase III | T-DM1 & Pertuzumab | Non-inferior PFS |
TH (Taxotere) TH (Taxol) |
Non-inferior PFS |
Chemotherapy
- Ado-trastuzumab emtansine (Kadcyla) 3.6 mg/kg IV once on day 1
21-day cycles
References
- 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
- Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, Martin M, Pienkowski T, Pivot X, Burris H 3rd, Petersen JA, Stanzel S, Strasak A, Patre M, Ellis P. Trastuzumab emtansine with or without pertuzumab versus trastuzumab plus taxane for human epidermal growth factor receptor 2-positive, advanced breast cancer: Primary results from the phase III MARIANNE study. J Clin Oncol. 2017 Jan 10;35(2):141-148. Epub 2016 Nov 7. link to original article link to PMC article contains verified protocol PubMed
Capecitabine, Bevacizumab, Trastuzumab
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Regimen
Study | Evidence | Efficacy |
---|---|---|
Martín et al. 2012 | Phase II | ORR: 73% (95% CI 62-82) |
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
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 link to PMC article PubMed
Capecitabine & Lapatinib
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Pivot et al. 2015 (CEREBEL) | Phase III | Capecitabine & Trastuzumab | Seems not superior |
Note: the primary endpoint of CEREBEL was incidence of CNS as site of first relapse; this was very low in both arms, with no statistically significant difference.
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO BID days 1 to 14
- Lapatinib (Tykerb) 1250 mg PO once per day
21-day cycles
References
- Pivot X, Manikhas A, Żurawski B, Chmielowska E, Karaszewska B, Allerton R, Chan S, Fabi A, Bidoli P, Gori S, Ciruelos E, Dank M, Hornyak L, Margolin S, Nusch A, Parikh R, Nagi F, DeSilvio M, Santillana S, Swaby RF, Semiglazov V. CEREBEL (EGF111438): A phase III, randomized, open-label study of lapatinib plus capecitabine versus trastuzumab plus capecitabine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2015 May 10;33(14):1564-73. Epub 2015 Jan 20. link to original article PubMed
Capecitabine & Trastuzumab
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XH: Xeloda (Capecitabine) & Herceptin
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Pivot et al. 2015 (CEREBEL) | Phase III | Capecitabine & Lapatanib | Seems not superior |
Note: the primary endpoint of CEREBEL was incidence of CNS as site of first relapse; this was very low in both arms, with no statistically significant difference.
Chemotherapy
- Capecitabine (Xeloda) 1250 mg/m2 PO BID 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
References
- Pivot X, Manikhas A, Żurawski B, Chmielowska E, Karaszewska B, Allerton R, Chan S, Fabi A, Bidoli P, Gori S, Ciruelos E, Dank M, Hornyak L, Margolin S, Nusch A, Parikh R, Nagi F, DeSilvio M, Santillana S, Swaby RF, Semiglazov V. CEREBEL (EGF111438): A phase III, randomized, open-label study of lapatinib plus capecitabine versus trastuzumab plus capecitabine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2015 May 10;33(14):1564-73. Epub 2015 Jan 20. link to original article contains protocol PubMed
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
TCH (Taxotere, Carboplatin)
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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
Treatment followed by trastuzumab maintenance.
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 (Taxol)
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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
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
T-DM1 & Pertuzumab
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T-DM1: Trastuzumab-DM1 (ado-Trastuzumab emtansine)
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Perez et al. 2016 (MARIANNE) | Phase III | T-DM1 | Non-inferior PFS |
TH (Taxotere) TH (Taxol) |
Non-inferior PFS |
Chemotherapy
- Ado-trastuzumab emtansine (Kadcyla) 3.6 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 cycles
References
- Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, Martin M, Pienkowski T, Pivot X, Burris H 3rd, Petersen JA, Stanzel S, Strasak A, Patre M, Ellis P. Trastuzumab emtansine with or without pertuzumab versus trastuzumab plus taxane for human epidermal growth factor receptor 2-positive, advanced breast cancer: Primary results from the phase III MARIANNE study. J Clin Oncol. 2017 Jan 10;35(2):141-148. Epub 2016 Nov 7. link to original article link to PMC article contains verified protocol PubMed
TH (Taxotere)
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TH: Taxotere (Docetaxel) & Herceptin (Trastuzumab)
HT: Herceptin (Trastuzumab) & Taxotere (Docetaxel)
Regimen #1, 75 mg/m2 docetaxel, q3wk trastuzumab
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Baselga et al. 2011 (CLEOPATRA) | Phase III (C) | THP | Inferior OS |
Hurvitz et al. 2013 (TDM4450g) | Randomized Phase II | T-DM1 | Seems to have inferior PFS |
Gelmon et al. 2015 (NCIC CTG MA.31) | Phase III (C) | Docetaxel & Lapatinib | Superior PFS |
Perez et al. 2016 (MARIANNE) | Phase III | T-DM1 | Non-inferior PFS |
T-DM1 & Pertuzumab | Non-inferior PFS | ||
TH (Taxol) | Not reported |
Note: Dose of docetaxel in Hurvitz et al. 2013 and MARIANNE was per investigator's discretion. CLEOPATRA has an unusual schedule with both medications being given on day 2 of cycle 1, due to this regimen being the control arm, in which patients in one arm received a placebo instead of pertuzumab on day 1. It is reasonable to assume that in practice, drugs in this regimen will be given on day 1 from the beginning.
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- 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
Subsequent treatment
- CLEOPATRA: If it is decided to no longer administer docetaxel with this regimen, then patients could continue to receive trastuzumab maintenance
- NCIC CTG MA.31: Trastuzumab maintenance, after 8 cycles
Regimen #2, 100 mg/m2 docetaxel, weekly trastuzumab
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Marty et al. 2005 (M77001) | Randomized Phase II | Docetaxel | Seems to have superior OS |
Valero et al. 2010 (BCIRG 007) | Phase III | TCH | Seems not superior |
Chemotherapy
- 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 (Taxotere)
- "Antiemetic premedication was mandatory" (no additional details given).
21-day cycle for 6 cycles (M77001) or 8 cycles (BCIRG 007)
Subsequent treatment
- M77001: Patients could receive docetaxel beyond six cycles at the discretion of the investigator. Otherwise, patients proceeded to trastuzumab maintenance.
- BCIRG 007: Trastuzumab maintenance
Regimen #3, 100 mg/m2 docetaxel, q3wk trastuzumab
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Andersson et al. 2010 (HERNATA)) | Phase III | Vinorelbine & Trastuzumab | Seems not superior |
Hurvitz et al. 2013 (TDM4450g) | Randomized Phase II | T-DM1 | Seems to have inferior PFS |
Gianni et al. 2013 (AVAREL) | Randomized Phase II | BTH | Might have inferior PFS |
Perez et al. 2016 (MARIANNE) | Phase III | T-DM1 | Non-inferior PFS |
T-DM1 & Pertuzumab | Non-inferior PFS | ||
TH (Taxol) | Not reported |
Note: In HERNATA, the day of docetaxel and trastuzumab were reversed in cycle 1. Dose of docetaxel in Hurvitz et al. 2013 and MARIANNE was per investigator's discretion.
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV over 60 minutes once on day 1 (see note)
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV over 90 minutes once on day 2 (see note)
- Cycle 2 onwards: 6 mg/kg IV over 30 minutes once on day 1
21-day cycles
Regimen #4, 3 out of 4 weeks
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Esteva et al. 2002 | Phase II | ||
Burstein et al. 2007 (TRAVIOTA) | Phase III | Vinorelbine & Trastuzumab | 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
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
- M77001: Marty M, Cognetti F, Maraninchi D, Snyder R, Mauriac L, Tubiana-Hulin M, Chan S, Grimes D, Antón A, Lluch A, Kennedy J, O'Byrne K, Conte P, Green M, Ward C, Mayne K, Extra JM. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol. 2005 Jul 1;23(19):4265-74. Epub 2005 May 23. link to original article 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
- BCIRG 007: Valero V, Forbes J, Pegram MD, Pienkowski T, Eiermann W, von Minckwitz G, Roche H, Martin M, Crown J, Mackey JR, Fumoleau P, Rolski J, Mrsic-Krmpotic Z, Jagiello-Gruszfeld A, Riva A, Buyse M, Taupin H, Sauter G, Press MF, Slamon DJ. Multicenter phase III randomized trial comparing docetaxel and trastuzumab with docetaxel, carboplatin, and trastuzumab as first-line chemotherapy for patients with HER2-gene-amplified metastatic breast cancer (BCIRG 007 study): two highly active therapeutic regimens. J Clin Oncol. 2011 Jan 10;29(2):149-56. Epub 2010 Nov 29. link to original article contains verified protocol PubMed
- HERNATA: Andersson M, Lidbrink E, Bjerre K, Wist E, Enevoldsen K, Jensen AB, Karlsson P, Tange UB, Sørensen PG, Møller S, Bergh J, Langkjer ST. Phase III randomized study comparing docetaxel plus trastuzumab with vinorelbine plus trastuzumab as first-line therapy of metastatic or locally advanced human epidermal growth factor receptor 2-positive breast cancer: the HERNATA study. J Clin Oncol. 2011 Jan 20;29(3):264-71. Epub 2010 Dec 13. link to original article contains verified protocol PubMed
- CLEOPATRA: Baselga J, Cortés J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, Clark E, Benyunes MC, Ross G, Swain SM; CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012 Jan 12;366(2):109-19. Epub 2011 Dec 7. link to original article 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 contains verified protocol link to PMC article PubMed
- Update: Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S, Clark E, Ross G, Benyunes MC, Cortés J; CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015 Feb 19;372(8):724-34. link to original article PubMed
- TDM4450g: Hurvitz SA, Dirix L, Kocsis J, Bianchi GV, Lu J, Vinholes J, Guardino E, Song C, Tong B, Ng V, Chu YW, Perez EA. Phase II randomized study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2013 Mar 20;31(9):1157-63. Epub 2013 Feb 4. Erratum in: J Clin Oncol. 2013 Aug 10;31(23):2977. link to original article contains verified protocol PubMed
- AVAREL: Gianni L, Romieu GH, Lichinitser M, Serrano SV, Mansutti M, Pivot X, Mariani P, Andre F, Chan A, Lipatov O, Chan S, Wardley A, Greil R, Moore N, Prot S, Pallaud C, Semiglazov V. AVEREL: a randomized phase III trial evaluating bevacizumab in combination with docetaxel and trastuzumab as first-line therapy for HER2-positive locally recurrent/metastatic breast cancer. J Clin Oncol. 2013 May 10;31(14):1719-25. Epub 2013 Apr 8. link to original article contains verified protocol PubMed
- NCIC CTG MA.31: Gelmon KA, Boyle FM, Kaufman B, Huntsman DG, Manikhas A, Di Leo A, Martin M, Schwartzberg LS, Lemieux J, Aparicio S, Shepherd LE, Dent S, Ellard SL, Tonkin K, Pritchard KI, Whelan TJ, Nomikos D, Nusch A, Coleman RE, Mukai H, Tjulandin S, Khasanov R, Rizel S, Connor AP, Santillana SL, Chapman JA, Parulekar WR. Lapatinib or trastuzumab plus taxane therapy for human epidermal growth factor receptor 2-positive advanced breast cancer: final results of NCIC CTG MA.31. J Clin Oncol. 2015 May 10;33(14):1574-83. Epub 2015 Mar 16. link to original article contains verified protocol PubMed
- MARIANNE: Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, Martin M, Pienkowski T, Pivot X, Burris H 3rd, Petersen JA, Stanzel S, Strasak A, Patre M, Ellis P. Trastuzumab emtansine with or without pertuzumab versus trastuzumab plus taxane for human epidermal growth factor receptor 2-positive, advanced breast cancer: Primary results from the phase III MARIANNE study. J Clin Oncol. 2017 Jan 10;35(2):141-148. Epub 2016 Nov 7. link to original article link to PMC article contains verified protocol PubMed
TH (Taxol)
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TH: Taxol (Paclitaxel), Herceptin (Trastuzumab)
TP: Trastuzumab, Paclitaxel
Regimen #1, weekly paclitaxel (80 mg/m2)
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Burstein et al. 2007 (TRAVIOTA) | Phase III | Vinorelbine & Trastuzumab | Might have inferior TTP |
Seidman et al. 2008 (CALGB 9840) | Phase III | TH, q3wk paclitaxel | Superior OS |
Perez et al. 2016 (MARIANNE) | Phase III | T-DM1 | Non-inferior PFS |
T-DM1 & Pertuzumab | Non-inferior PFS | ||
TH (Taxotere) | Not reported |
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
Continued until progression
Regimen #2, 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 (the day before the first dose of paclitaxel), then 2 mg/kg IV once per week
Continued until progression
Regimen #3, paclitaxel 3 weeks out of 4, 6 cycles
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Gelmon et al. 2015 (NCIC CTG MA.31) | Phase III (C) | Lapatinib & Paclitaxel | Superior PFS |
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
28-day cycle for 6 cycles
Subsequent treatment
- Trastuzumab maintenance
Regimen #4, paclitaxel 3 weeks out of 4, indefinite
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Hurvitz et al. 2015 (BOLERO-1) | Phase III (C) | Everolimus, Paclitaxel, Trastuzumab | Seems not superior |
Awada et al. 2016 (NEfERT-T) | Phase III (C) | 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
28-day cycles
Regimen #5, 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
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
- TRAVIOTA: Burstein HJ, Keshaviah A, Baron AD, Hart RD, Lambert-Falls R, Marcom PK, Gelman R, Winer EP. Trastuzumab plus vinorelbine or taxane chemotherapy for HER2-overexpressing metastatic breast cancer: the trastuzumab and vinorelbine or taxane study. Cancer. 2007 Sep 1;110(5):965-72. link to original article PubMed
- CALGB 9840: Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom PK, Gipson G, Burstein H, Lake D, Shapiro CL, Ungaro P, Norton L, Winer E, Hudis C. Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol. 2008 Apr 1;26(10):1642-9. link to original article PubMed
- NCIC CTG MA.31: Gelmon KA, Boyle FM, Kaufman B, Huntsman DG, Manikhas A, Di Leo A, Martin M, Schwartzberg LS, Lemieux J, Aparicio S, Shepherd LE, Dent S, Ellard SL, Tonkin K, Pritchard KI, Whelan TJ, Nomikos D, Nusch A, Coleman RE, Mukai H, Tjulandin S, Khasanov R, Rizel S, Connor AP, Santillana SL, Chapman JA, Parulekar WR. Lapatinib or trastuzumab plus taxane therapy for human epidermal growth factor receptor 2-positive advanced breast cancer: final results of NCIC CTG MA.31. J Clin Oncol. 2015 May 10;33(14):1574-83. Epub 2015 Mar 16. link to original article contains verified protocol PubMed
- BOLERO-1: Hurvitz SA, Andre F, Jiang Z, Shao Z, Mano MS, Neciosup SP, Tseng LM, Zhang Q, Shen K, Liu D, Dreosti LM, Burris HA, Toi M, Buyse ME, Cabaribere D, Lindsay MA, Rao S, Pacaud LB, Taran T, Slamon D. Combination of everolimus with trastuzumab plus paclitaxel as first-line treatment for patients with HER2-positive advanced breast cancer (BOLERO-1): a phase 3, randomised, double-blind, multicentre trial. Lancet Oncol. 2015 Jul;16(7):816-29. Epub 2015 Jun 16. link to original article PubMed
- MARIANNE: Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, Martin M, Pienkowski T, Pivot X, Burris H 3rd, Petersen JA, Stanzel S, Strasak A, Patre M, Ellis P. Trastuzumab emtansine with or without pertuzumab versus trastuzumab plus taxane for human epidermal growth factor receptor 2-positive, advanced breast cancer: Primary results from the phase III MARIANNE study. J Clin Oncol. 2017 Jan 10;35(2):141-148. Epub 2016 Nov 7. link to original article link to PMC article contains verified protocol PubMed
- NEfERT-T: Awada A, Colomer R, Inoue K, Bondarenko I, Badwe RA, Demetriou G, Lee SC, Mehta AO, Kim SB, Bachelot T, Goswami C, Deo S, Bose R, Wong A, Xu F, Yao B, Bryce R, Carey LA. neratinib plus paclitaxel vs trastuzumab plus paclitaxel in previously untreated metastatic ERBB2-positive breast cancer: The NEfERT-T randomized clinical trial. JAMA Oncol. 2016 Dec 1;2(12):1557-1564. link to original article contains verified protocol PubMed
THP (Taxotere)
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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
Subsequent treatment
- If it is decided to no longer administer docetaxel, then patients could continue to receive pertuzumab & trastuzumab maintenance.
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 contains verified protocol link to PMC article PubMed
- Update: Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S, Clark E, Ross G, Benyunes MC, Cortés J; CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015 Feb 19;372(8):724-34. link to original article PubMed
TL (Taxol)
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TL: Taxol (Paclitaxel) & Lapatinib
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Guan et al. 2013 | Phase III (E) | Paclitaxel | Seems to have superior OS |
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
- Lapatinib (Tykerb) 1500 mg PO once per day
28-day cycles
References
- Guan Z, Xu B, DeSilvio ML, Shen Z, Arpornwirat W, Tong Z, Lorvidhaya V, Jiang Z, Yang J, Makhson A, Leung WL, Russo MW, Newstat B, Wang L, Chen G, Oliva C, Gomez H. Randomized trial of lapatinib versus placebo added to paclitaxel in the treatment of human epidermal growth factor receptor 2-overexpressing metastatic breast cancer. J Clin Oncol. 2013 Jun 1;31(16):1947-53. Epub 2013 Mar 18. link to original article contains verified protocol PubMed
- NCIC CTG MA.31: Gelmon KA, Boyle FM, Kaufman B, Huntsman DG, Manikhas A, Di Leo A, Martin M, Schwartzberg LS, Lemieux J, Aparicio S, Shepherd LE, Dent S, Ellard SL, Tonkin K, Pritchard KI, Whelan TJ, Nomikos D, Nusch A, Coleman RE, Mukai H, Tjulandin S, Khasanov R, Rizel S, Connor AP, Santillana SL, Chapman JA, Parulekar WR. Lapatinib or trastuzumab plus taxane therapy for human epidermal growth factor receptor 2-positive advanced breast cancer: final results of NCIC CTG MA.31. J Clin Oncol. 2015 May 10;33(14):1574-83. Epub 2015 Mar 16. link to original article PubMed
Vinorelbine & Trastuzumab
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Regimen #1, vinorelbine 25 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Burstein et al. 2007 (TRAVIOTA) | Phase III | TH (Taxotere) TH (Taxol) |
Might have superior TTP |
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
Regimen #2, vinorelbine 30 mg/m2, 2 out of 3 weeks
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Andersson et al. 2010 (HERNATA) | Phase III | TH (Taxotere) | Seems not superior |
Chemotherapy
- Vinorelbine (Navelbine) 30 mg/m2 IV once per day on days 1 & 8
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV over 90 minutes once on day 1
- Cycle 2 onwards: 6 mg/kg IV over 30 minutes once on day 1
21-day cycles
Regimen #3, vinorelbine 35 mg/m2, 2 out of 3 weeks
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Andersson et al. 2010 (HERNATA) | Phase III | TH (Taxotere) | Seems not superior |
Chemotherapy
- Vinorelbine (Navelbine) 35 mg/m2 IV once per day on days 1 & 8
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV over 90 minutes once on day 1
- Cycle 2 onwards: 6 mg/kg IV over 30 minutes once on day 1
21-day cycles
References
- TRAVIOTA: Burstein HJ, Keshaviah A, Baron AD, Hart RD, Lambert-Falls R, Marcom PK, Gelman R, Winer EP. Trastuzumab plus vinorelbine or taxane chemotherapy for HER2-overexpressing metastatic breast cancer: the trastuzumab and vinorelbine or taxane study. Cancer. 2007 Sep 1;110(5):965-72. link to original article PubMed
- HERNATA: Andersson M, Lidbrink E, Bjerre K, Wist E, Enevoldsen K, Jensen AB, Karlsson P, Tange UB, Sørensen PG, Møller S, Bergh J, Langkjer ST. Phase III randomized study comparing docetaxel plus trastuzumab with vinorelbine plus trastuzumab as first-line therapy of metastatic or locally advanced human epidermal growth factor receptor 2-positive breast cancer: the HERNATA study. J Clin Oncol. 2011 Jan 20;29(3):264-71. Epub 2010 Dec 13. link to original article contains verified protocol PubMed
Metastatic or unresectable disease, subsequent lines
Ado-trastuzumab emtansine monotherapy
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Example orders
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Verma et al. 2012 (EMILIA) | Phase III | Capecitabine & Lapatinib | Superior OS |
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
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 link to PMC article PubMed
- Update: Diéras V, Miles D, Verma S, Pegram M, Welslau M, Baselga J, Krop IE, Blackwell K, Hoersch S, Xu J, Green M, Gianni L. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2017 Jun;18(6):732-742. Epub 2017 May 16. link to original article link to PMC article PubMed
- 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 article PubMed
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 |
Pivot et al. 2015 (CEREBEL) | Phase III | Capecitabine & Trastuzumab | Seems not superior |
Note: the primary endpoint of CEREBEL was incidence of CNS as site of first relapse; this was very low in both arms, with no statistically significant difference.
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 contains protocol 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 link to PMC 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 link to PMC article PubMed
- Update: Diéras V, Miles D, Verma S, Pegram M, Welslau M, Baselga J, Krop IE, Blackwell K, Hoersch S, Xu J, Green M, Gianni L. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2017 Jun;18(6):732-742. Epub 2017 May 16. link to original article link to PMC article PubMed
- Pivot X, Manikhas A, Żurawski B, Chmielowska E, Karaszewska B, Allerton R, Chan S, Fabi A, Bidoli P, Gori S, Ciruelos E, Dank M, Hornyak L, Margolin S, Nusch A, Parikh R, Nagi F, DeSilvio M, Santillana S, Swaby RF, Semiglazov V. CEREBEL (EGF111438): A phase III, randomized, open-label study of lapatinib plus capecitabine versus trastuzumab plus capecitabine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2015 May 10;33(14):1564-73. Epub 2015 Jan 20. link to original article PubMed
Capecitabine & Neratinib
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Regimen
Study | Evidence | ORR |
---|---|---|
Saura et al. 2014 | Phase I/II | 64% |
Note: this is the MTD dose from the phase II portion.
Chemotherapy
- Capecitabine (Xeloda) 750 mg/m2 PO BID days 1 to 14
- Neratinib (Nerlynx) 240 mg PO once per day
21-day cycles
References
- Saura C, Garcia-Saenz JA, Xu B, Harb W, Moroose R, Pluard T, Cortés J, Kiger C, Germa C, Wang K, Martin M, Baselga J, Kim SB. Safety and efficacy of neratinib in combination with capecitabine in patients with metastatic human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2014 Nov 10;32(32):3626-33. Epub 2014 Oct 6. link to original article contains verified protocol PubMed
Capecitabine, Pertuzumab, Trastuzumab
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Urruticoechea et al. 2017 (PHEREXA) | Phase III | Capecitabine & Trastuzumab | Might have superior PFS |
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO BID days 1 to 14
- Pertuzumab (Perjeta) as follows:
- Cycle 1: 840 mg IV once on day 1
- Cycle 2 onwards: 420 mg IV once on day 1
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
References
- Urruticoechea A, Rizwanullah M, Im SA, Ruiz ACS, Láng I, Tomasello G, Douthwaite H, Badovinac Crnjevic T, Heeson S, Eng-Wong J, Muñoz M. Randomized phase III trial of trastuzumab plus capecitabine with or without pertuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who experienced disease progression during or after trastuzumab-based therapy. J Clin Oncol. 2017 Sep 10;35(26):3030-3038. Epub 2017 Apr 24. link to original article contains verified protocol PubMed
Capecitabine & Trastuzumab
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XH: Xeloda (Capecitabine) & Herceptin
Regimen #1
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bartsch et al. 2007 | Phase II | ORR: 20% | |
Pivot et al. 2015 (CEREBEL) | Phase III | Capecitabine & Lapatanib | Seems not superior |
Urruticoechea et al. 2017 (PHEREXA) | Phase III | Capecitabine, Pertuzumab, Trastuzumab | Might have inferior PFS |
Note: the only difference between this and variant #2 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.
Chemotherapy
- Capecitabine (Xeloda) 1250 mg/m2 PO BID 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
Regimen #2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2009 (GBG 26/BIG 3-05) | Phase III | Capecitabine | Seems to have superior TTP |
This is a continuation of trastuzumab so there is no loading dose.
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
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 contains verified protocol 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 contains verified protocol 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
- Pivot X, Manikhas A, Żurawski B, Chmielowska E, Karaszewska B, Allerton R, Chan S, Fabi A, Bidoli P, Gori S, Ciruelos E, Dank M, Hornyak L, Margolin S, Nusch A, Parikh R, Nagi F, DeSilvio M, Santillana S, Swaby RF, Semiglazov V. CEREBEL (EGF111438): A phase III, randomized, open-label study of lapatinib plus capecitabine versus trastuzumab plus capecitabine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2015 May 10;33(14):1564-73. Epub 2015 Jan 20. link to original article contains protocol PubMed
- Urruticoechea A, Rizwanullah M, Im SA, Ruiz ACS, Láng I, Tomasello G, Douthwaite H, Badovinac Crnjevic T, Heeson S, Eng-Wong J, Muñoz M. Randomized phase III trial of trastuzumab plus capecitabine with or without pertuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who experienced disease progression during or after trastuzumab-based therapy. J Clin Oncol. 2017 Sep 10;35(26):3030-3038. Epub 2017 Apr 24. link to original article contains verified protocol PubMed
Lapatinib monotherapy
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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, then 2 mg/kg IV once per week
(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 link to PMC article PubMed
Vinorelbine & Trastuzumab
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
André et al. 2014 (BOLERO-3) | Phase III (C) | Everolimus, Trastuzumab, Vinorelbine | Inferior PFS |
Harbeck et al. 2016 (LUX-Breast 1) | Phase III (C) | 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
- 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 original article contains verified protocol PubMed
Maintenance for metastatic or unresectable disease
Pertuzumab & Trastuzumab
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Regimen
Study | Evidence |
---|---|
Baselga et al. 2011 (CLEOPATRA) | Non-randomized portion of RCT |
Preceding treatment
- THP (Taxotere) for at least 6 cycles
Chemotherapy
- Pertuzumab (Perjeta) 420 mg IV once on day 1
- Trastuzumab (Herceptin) 6 mg/kg IV once on day 1
21-day cycles
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 contains verified protocol link to PMC article PubMed
- Update: Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S, Clark E, Ross G, Benyunes MC, Cortés J; CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015 Feb 19;372(8):724-34. link to original article PubMed
Trastuzumab monotherapy
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Regimen #1, q3wk dosing
Study | Evidence |
---|---|
Valero et al. 2010 (BCIRG 007) | Non-randomized portion of RCT |
Baselga et al. 2011 (CLEOPATRA) | Non-randomized portion of RCT |
Gelmon et al. 2015 (NCIC CTG MA.31) | Non-randomized portion of RCT |
Preceding treatment
- BCIRG 0007: TH (Taxotere) x 8 versus TCH (Taxotere) x 8
- CLEOPATRA: TH (Taxotere)
- NCIC CTG MA.31: TH (Taxol) x 6 or TH (Taxotere) x 8
Chemotherapy
- Trastuzumab (Herceptin) 6 mg/kg IV once on day 1
21-day cycles
Regimen #2, weekly dosing
Study | Evidence |
---|---|
Marty et al. 2005 (M77001) | Non-randomized portion of RCT |
Preceding treatment
- TH (Taxotere) for at least 6 cycles
Chemotherapy
- Trastuzumab (Herceptin) 2 mg/kg IV once per week
Given until progression of disease or unacceptable toxicity
References
- M77001: Marty M, Cognetti F, Maraninchi D, Snyder R, Mauriac L, Tubiana-Hulin M, Chan S, Grimes D, Antón A, Lluch A, Kennedy J, O'Byrne K, Conte P, Green M, Ward C, Mayne K, Extra JM. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol. 2005 Jul 1;23(19):4265-74. Epub 2005 May 23. link to original article contains verified protocol PubMed
- BCIRG 007: Valero V, Forbes J, Pegram MD, Pienkowski T, Eiermann W, von Minckwitz G, Roche H, Martin M, Crown J, Mackey JR, Fumoleau P, Rolski J, Mrsic-Krmpotic Z, Jagiello-Gruszfeld A, Riva A, Buyse M, Taupin H, Sauter G, Press MF, Slamon DJ. Multicenter phase III randomized trial comparing docetaxel and trastuzumab with docetaxel, carboplatin, and trastuzumab as first-line chemotherapy for patients with HER2-gene-amplified metastatic breast cancer (BCIRG 007 study): two highly active therapeutic regimens. J Clin Oncol. 2011 Jan 10;29(2):149-56. Epub 2010 Nov 29. link to original article contains verified protocol PubMed
- CLEOPATRA: Baselga J, Cortés J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, Clark E, Benyunes MC, Ross G, Swain SM; CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012 Jan 12;366(2):109-19. Epub 2011 Dec 7. link to original article 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 contains verified protocol link to PMC article PubMed
- Update: Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S, Clark E, Ross G, Benyunes MC, Cortés J; CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015 Feb 19;372(8):724-34. link to original article PubMed
- NCIC CTG MA.31: Gelmon KA, Boyle FM, Kaufman B, Huntsman DG, Manikhas A, Di Leo A, Martin M, Schwartzberg LS, Lemieux J, Aparicio S, Shepherd LE, Dent S, Ellard SL, Tonkin K, Pritchard KI, Whelan TJ, Nomikos D, Nusch A, Coleman RE, Mukai H, Tjulandin S, Khasanov R, Rizel S, Connor AP, Santillana SL, Chapman JA, Parulekar WR. Lapatinib or trastuzumab plus taxane therapy for human epidermal growth factor receptor 2-positive advanced breast cancer: final results of NCIC CTG MA.31. J Clin Oncol. 2015 May 10;33(14):1574-83. Epub 2015 Mar 16. link to original article contains verified protocol PubMed
Additional resources
- Gail model Breast Cancer Risk Assessment Tool
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- Adjuvant! Online (requires login)
- My Cancer Genome