Triple Negative Breast Cancer Plant Based Diet
Section editor | |
---|---|
| H. Deepika Fernandes, MD, FACP University of North Dakota Bismarck, ND |
Note: this page has regimens which are specific to breast cancer that is triple negative. Please see the breast cancer page for other chemotherapy regimens.
Guidelines
ASCO
- 2021: Korde et al. Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer: ASCO Guideline
- 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
St Gallen Breast Guidelines
- 2019: Burstein et al. Estimating the benefits of therapy for early-stage breast cancer: the St. Gallen International Consensus Guidelines for the primary therapy of early breast cancer 2019
Older
- 2017: Curigliano et al. St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2017
- 2015: Coates et al. Tailoring therapies—improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015
Neoadjuvant chemotherapy
Cyclophosphamide & Doxorubicin (AC)
AC: A driamycin (Doxorubicin) & C yclophosphamide
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rugo et al. 2016 (I-SPY 2) | 2010-2012 | Non-randomized portion of RCT | ||
Schmid et al. 2020 (KEYNOTE-522) | 2017-2018 | Phase III (C) | AC & Pembrolizumab | Inferior pCR rate |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- I-SPY 2: T x 12 wk versus Paclitaxel & VC x 12 wk
- KEYNOTE-522: Carboplatin & Paclitaxel x 4
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- Surgery
References
- I-SPY 2: Rugo HS, Olopade OI, DeMichele A, Yau C, van 't Veer LJ, Buxton MB, Hogarth M, Hylton NM, Paoloni M, Perlmutter J, Symmans WF, Yee D, Chien AJ, Wallace AM, Kaplan HG, Boughey JC, Haddad TC, Albain KS, Liu MC, Isaacs C, Khan QJ, Lang JE, Viscusi RK, Pusztai L, Moulder SL, Chui SY, Kemmer KA, Elias AD, Edmiston KK, Euhus DM, Haley BB, Nanda R, Northfelt DW, Tripathy D, Wood WC, Ewing C, Schwab R, Lyandres J, Davis SE, Hirst GL, Sanil A, Berry DA, Esserman LJ; I-SPY 2 Investigators. Adaptive randomization of veliparib-carboplatin treatment in breast cancer. N Engl J Med. 2016 Jul 7;375(1):23-34. link to original article contains verified protocol link to PMC article PubMed NCT01042379
- KEYNOTE-522: Schmid P, Cortes J, Pusztai L, McArthur H, Kümmel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Foukakis T, Fasching PA, Cardoso F, Untch M, Jia L, Karantza V, Zhao J, Aktan G, Dent R, O'Shaughnessy J; KEYNOTE-522 Investigators. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020 Feb 27;382(9):810-821. link to original article PubMed NCT03036488
Dose-dense Cyclophosphamide & Doxorubicin (ddAC)
ddAC: d ose- d ense A driamycin (Doxorubicin) & C yclophosphamide
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Sikov et al. 2014 (CALGB 40603) | 2009-2012 | Non-randomized portion of RCT |
Rugo et al. 2016 (I-SPY 2) | 2010-2012 | Non-randomized portion of RCT |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- CALGB 40603: Carboplatin & Bevacizumab x 4 versus Carboplatin & Paclitaxel x 4 versus Carboplatin, Paclitaxel, Bevacizumab versus T x 12 wk
- I-SPY2: T x 12 wk versus Paclitaxel & VC x 12 wk
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Supportive medications
- G-CSF
14-day cycle for 4 cycles
Subsequent treatment
- Surgery
References
- CALGB 40603: Sikov WM, Berry DA, Perou CM, Singh B, Cirrincione CT, Tolaney SM, Kuzma CS, Pluard TJ, Somlo G, Port ER, Golshan M, Bellon JR, Collyar D, Hahn OM, Carey LA, Hudis CA, Winer EP. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J Clin Oncol. 2015 Jan 1;33(1):13-21. Epub 2014 Aug 4. link to original article link to PMC article contains verified protocol PubMed NCT00861705
- I-SPY 2: Rugo HS, Olopade OI, DeMichele A, Yau C, van 't Veer LJ, Buxton MB, Hogarth M, Hylton NM, Paoloni M, Perlmutter J, Symmans WF, Yee D, Chien AJ, Wallace AM, Kaplan HG, Boughey JC, Haddad TC, Albain KS, Liu MC, Isaacs C, Khan QJ, Lang JE, Viscusi RK, Pusztai L, Moulder SL, Chui SY, Kemmer KA, Elias AD, Edmiston KK, Euhus DM, Haley BB, Nanda R, Northfelt DW, Tripathy D, Wood WC, Ewing C, Schwab R, Lyandres J, Davis SE, Hirst GL, Sanil A, Berry DA, Esserman LJ; I-SPY 2 Investigators. Adaptive randomization of veliparib-carboplatin treatment in breast cancer. N Engl J Med. 2016 Jul 7;375(1):23-34. link to original article contains verified protocol link to PMC article PubMed NCT01042379
- IMpassion031: Mittendorf EA, Zhang H, Barrios CH, Saji S, Jung KH, Hegg R, Koehler A, Sohn J, Iwata H, Telli ML, Ferrario C, Punie K, Penault-Llorca F, Patel S, Duc AN, Liste-Hermoso M, Maiya V, Molinero L, Chui SY, Harbeck N. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet. 2020 Sep 18:S0140-6736(20)31953-X. Epub ahead of print. link to original article PubMed NCT03197935
ddAC & Atezolizumab
ddAC & Atezolizumab: d ose- d ense A driamycin (Doxorubicin), C yclophosphamide, Atezolizumab
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mittendorf et al. 2020 (IMpassion031) | 2017-2019 | Phase III (E-esc) | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- nab-Paclitaxel & Atezolizumab
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Immunotherapy
- Atezolizumab (Tecentriq) 840 mg IV once on day 1
Supportive medications
- G-CSF
14-day cycle for 4 cycles
Subsequent treatment
- Surgery, then Atezolizumab x 11
References
- IMpassion031: Mittendorf EA, Zhang H, Barrios CH, Saji S, Jung KH, Hegg R, Koehler A, Sohn J, Iwata H, Telli ML, Ferrario C, Punie K, Penault-Llorca F, Patel S, Duc AN, Liste-Hermoso M, Maiya V, Molinero L, Chui SY, Harbeck N. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet. 2020 Sep 18:S0140-6736(20)31953-X. Epub ahead of print. link to original article contains verified protocol PubMed NCT03197935
AC & Pembrolizumab
AC & Pembrolizumab: A driamycin (Doxorubicin), C yclophosphamide, Pembrolizumab
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Schmid et al. 2020 (KEYNOTE-522) | 2017-2018 | Phase III (E-RT-esc) | AC | Superior pCR rate |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Carboplatin, Paclitaxel, Pembrolizumab x 4
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Immunotherapy
- Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- Surgery, then Pembrolizumab x 9
References
- KEYNOTE-522: Schmid P, Cortes J, Pusztai L, McArthur H, Kümmel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Foukakis T, Fasching PA, Cardoso F, Untch M, Jia L, Karantza V, Zhao J, Aktan G, Dent R, O'Shaughnessy J; KEYNOTE-522 Investigators. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020 Feb 27;382(9):810-821. link to original article contains verified protocol PubMed NCT03036488
Carboplatin & Docetaxel
CbD: C ar b oplatin & D ocetaxel
Regimen
Study | Years of enrollment | Evidence | Efficacy |
---|---|---|---|
Sharma et al. 2016 (GOMHGUGM022011) | 2010-2015 | Phase II | 56-59% pCR rate |
Sharma et al. 2016 (PROGECT) | 2011-2015 | Phase II | 56-59% pCR rate |
Note: Sharma et al. 2016 was a combined analysis of two separate clinical trials.
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
21-day cycle for 6 cycles
Subsequent treatment
- Surgery
References
- PROGECT: Sharma P, López-Tarruella S, García-Saenz JA, Ward C, Connor CS, Gómez HL, Prat A, Moreno F, Jerez-Gilarranz Y, Barnadas A, Picornell AC, Del Monte-Millán M, Gonzalez-Rivera M, Massarrah T, Pelaez-Lorenzo B, Palomero MI, González Del Val R, Cortes J, Fuentes Rivera H, Bretel Morales D, Márquez-Rodas I, Perou CM, Wagner JL, Mammen JM, McGinness MK, Klemp JR, Amin AL, Fabian CJ, Heldstab J, Godwin AK, Jensen RA, Kimler BF, Khan QJ, Martin M. Efficacy of neoadjuvant carboplatin plus docetaxel in triple-negative breast cancer: Combined analysis of two cohorts. Clin Cancer Res. 2017 Feb 1;23(3):649-657. Epub 2016 Jun 14. link to original article contains protocol link to PMC article PubMed NCT02302742
- GOMHGUGM022011: Sharma P, López-Tarruella S, García-Saenz JA, Ward C, Connor CS, Gómez HL, Prat A, Moreno F, Jerez-Gilarranz Y, Barnadas A, Picornell AC, Del Monte-Millán M, Gonzalez-Rivera M, Massarrah T, Pelaez-Lorenzo B, Palomero MI, González Del Val R, Cortes J, Fuentes Rivera H, Bretel Morales D, Márquez-Rodas I, Perou CM, Wagner JL, Mammen JM, McGinness MK, Klemp JR, Amin AL, Fabian CJ, Heldstab J, Godwin AK, Jensen RA, Kimler BF, Khan QJ, Martin M. Efficacy of neoadjuvant carboplatin plus docetaxel in triple-negative breast cancer: Combined analysis of two cohorts. Clin Cancer Res. 2017 Feb 1;23(3):649-657. Epub 2016 Jun 14. link to original article contains protocol link to PMC article PubMed NCT01560663
- CH-BC-007: NCT01150513
Carboplatin & Paclitaxel (CP)
Regimen variant #1, 5/80
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
(PARTNER) | 2016-ongoing | Phase III (C) | CP & Olaparib | In progress |
Note: Dosing information is from CT.gov.
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
21-day cycle for 4 cycles
Subsequent treatment
- Surgery
Regimen variant #2, 6/80
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sikov et al. 2014 (CALGB 40603) | 2009-2012 | Phase III (E-esc) | Paclitaxel | Superior pCR rate |
Loibl et al. 2018 (BrighTNess) | 2014-2016 | Phase III (E-esc) | 1. CP & Veliparib | Did not meet primary endpoint of pCR rate |
2. Paclitaxel | Not reported in abstract |
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
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
21-day cycle for 4 cycles
Subsequent treatment
- CALGB 40603: ddAC x 4, then surgery
- BrighTNess: AC x 4 or ddAC x 4, then surgery
References
- CALGB 40603: Sikov WM, Berry DA, Perou CM, Singh B, Cirrincione CT, Tolaney SM, Kuzma CS, Pluard TJ, Somlo G, Port ER, Golshan M, Bellon JR, Collyar D, Hahn OM, Carey LA, Hudis CA, Winer EP. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J Clin Oncol. 2015 Jan 1;33(1):13-21. Epub 2014 Aug 4. link to original article link to PMC article contains verified protocol PubMed NCT00861705
- BrighTNess: Loibl S, O'Shaughnessy J, Untch M, Sikov WM, Rugo HS, McKee MD, Huober J, Golshan M, von Minckwitz G, Maag D, Sullivan D, Wolmark N, McIntyre K, Ponce Lorenzo JJ, Metzger Filho O, Rastogi P, Symmans WF, Liu X, Geyer CE Jr. Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial. Lancet Oncol. 2018 Apr;19(4):497-509. Epub 2018 Feb 28. link to original article contain protocol PubMed NCT02032277
- KEYNOTE-522: Schmid P, Cortes J, Pusztai L, McArthur H, Kümmel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Foukakis T, Fasching PA, Cardoso F, Untch M, Jia L, Karantza V, Zhao J, Aktan G, Dent R, O'Shaughnessy J; KEYNOTE-522 Investigators. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020 Feb 27;382(9):810-821. link to original article PubMed NCT03036488
- PARTNER: NCT03150576
Carboplatin & Paclitaxel (CP) & Pembrolizumab
Regimen variant #1, q3wk carboplatin
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Schmid et al. 2020 (KEYNOTE-522) | 2017-2018 | Phase III (E-RT-esc) | Carboplatin & Paclitaxel | Superior pCR rate |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Immunotherapy
- Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- AC & Pembrolizumab x 4 or EC & Pembrolizumab x 4, then surgery, then Pembrolizumab x 9
Regimen variant #2, weekly carboplatin
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Schmid et al. 2020 (KEYNOTE-522) | 2017-2018 | Phase III (E-RT-esc) | Carboplatin & Paclitaxel | Superior pCR rate |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Chemotherapy
- Carboplatin (Paraplatin) AUC 1.5 IV once per day on days 1, 8, 15
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Immunotherapy
- Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- AC & Pembrolizumab x 4 or EC & Pembrolizumab x 4, then surgery, then Pembrolizumab x 9
References
- KEYNOTE-522: Schmid P, Cortes J, Pusztai L, McArthur H, Kümmel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Foukakis T, Fasching PA, Cardoso F, Untch M, Jia L, Karantza V, Zhao J, Aktan G, Dent R, O'Shaughnessy J; KEYNOTE-522 Investigators. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020 Feb 27;382(9):810-821. link to original article contains verified protocol PubMed NCT03036488
Carboplatin & nab-Paclitaxel
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gluz et al. 2018 (WSG-ADAPT-TN) | 2013-2015 | Phase III (E-switch-ic) | Gemcitabine & nab-Paclitaxel | Superior pCR rate |
Chemotherapy
- Carboplatin (Paraplatin) AUC 2 IV once per day on days 1 & 8
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 125 mg/m2 IV once per day on days 1 & 8
21-day cycle for 4 cycles
Subsequent treatment
- Surgery
References
- WSG-ADAPT-TN: Gluz O, Nitz U, Liedtke C, Christgen M, Grischke EM, Forstbauer H, Braun M, Warm M, Hackmann J, Uleer C, Aktas B, Schumacher C, Bangemann N, Lindner C, Kuemmel S, Clemens M, Potenberg J, Staib P, Kohls A, von Schumann R, Kates R, Kates R, Schumacher J, Wuerstlein R, Kreipe HH, Harbeck N; West German Study Group. Comparison of neoadjuvant nab-paclitaxel+carboplatin vs nab-paclitaxel+gemcitabine in triple-negative breast cancer: randomized WSG-ADAPT-TN trial results. J Natl Cancer Inst. 2018 Jun 1;110(6):628-637. link to original article contains verified protocol PubMed NCT01815242
Cisplatin monotherapy
Regimen
Study | Years of enrollment | Evidence | Efficacy |
---|---|---|---|
Silver et al. 2010 (DFCI 04-183) | 2004-NR | Phase II | 50% good pathologic response |
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- Surgery
References
- DFCI 04-183: Silver DP, Richardson AL, Eklund AC, Wang ZC, Szallasi Z, Li Q, Juul N, Leong CO, Calogrias D, Buraimoh A, Fatima A, Gelman RS, Ryan PD, Tung NM, De Nicolo A, Ganesan S, Miron A, Colin C, Sgroi DC, Ellisen LW, Winer EP, Garber JE. Efficacy of neoadjuvant cisplatin in triple-negative breast cancer. J Clin Oncol. 2010 Mar 1;28(7):1145-53. Epub 2010 Jan 25. link to original article contains verified protocol link to PMC article PubMed NCT00148694
Cisplatin & Bevacizumab
Regimen
Study | Evidence | Efficacy |
---|---|---|
Ryan et al. 2009 | Phase II | 26% clinical CR |
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
Targeted therapy
- Bevacizumab (Avastin) as follows:
- Cycles 1 to 3: 15 mg/kg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- Surgery
References
- Abstract: P. D. Ryan, N. M. Tung, S. J. Isakoff, M. Golshan, A. Richardson, A. D. Corben, B. L. Smith, R. Gelman, E. P. Winer, and J. E. Garber. Neoadjuvant cisplatin and bevacizumab in triple negative breast cancer (TNBC): Safety and efficacy. Journal of Clinical Oncology 2009 27:15_suppl, 551-551. link to abstract
Docetaxel & Bevacizumab
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2012 (GeparQuinto) | 2007-2010 | Phase III (E-esc) | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- EC & Bevacizumab x 4
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
Targeted therapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- Surgery
References
- GeparQuinto: von Minckwitz G, Eidtmann H, Rezai M, Fasching PA, Tesch H, Eggemann H, Schrader I, Kittel K, Hanusch C, Kreienberg R, Solbach C, Gerber B, Jackisch C, Kunz G, Blohmer JU, Huober J, Hauschild M, Fehm T, Müller BM, Denkert C, Loibl S, Nekljudova V, Untch M; German Breast Group; Arbeitsgemeinschaft Gynäkologische Onkologie–Breast Study Group. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med. 2012 Jan 26;366(4):299-309. link to original article contains verified protocol PubMed NCT00567554
Cyclophosphamide & Epirubicin (EC)
EC: E pirubicin & C yclophosphamide
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Schmid et al. 2020 (KEYNOTE-522) | 2017-2018 | Phase III (C) | EC & Pembrolizumab | Inferior pCR rate |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Carboplatin & Paclitaxel x 4
Chemotherapy
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- Surgery
References
- KEYNOTE-522: Schmid P, Cortes J, Pusztai L, McArthur H, Kümmel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Foukakis T, Fasching PA, Cardoso F, Untch M, Jia L, Karantza V, Zhao J, Aktan G, Dent R, O'Shaughnessy J; KEYNOTE-522 Investigators. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020 Feb 27;382(9):810-821. link to original article PubMed NCT03036488
Cyclophosphamide & Epirubicin (EC) & Bevacizumab
EC & Bevacizumab: E pirubicin, C yclophosphamide, Bevacizumab
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
von Minckwitz et al. 2012 (GeparQuinto) | 2007-2010 | Phase III (E-esc) | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Chemotherapy
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Targeted therapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- Docetaxel & Bevacizumab, then surgery
References
- GeparQuinto: von Minckwitz G, Eidtmann H, Rezai M, Fasching PA, Tesch H, Eggemann H, Schrader I, Kittel K, Hanusch C, Kreienberg R, Solbach C, Gerber B, Jackisch C, Kunz G, Blohmer JU, Huober J, Hauschild M, Fehm T, Müller BM, Denkert C, Loibl S, Nekljudova V, Untch M; German Breast Group; Arbeitsgemeinschaft Gynäkologische Onkologie–Breast Study Group. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med. 2012 Jan 26;366(4):299-309. link to original article contains verified protocol PubMed NCT00567554
Cyclophosphamide & Epirubicin (EC) & Pembrolizumab
EC & Pembrolizumab: E pirubicin, C yclophosphamide, Pembrolizumab
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Schmid et al. 2020 (KEYNOTE-522) | 2017-2018 | Phase III (E-RT-esc) | EC | Superior pCR rate |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Carboplatin, Paclitaxel, Pembrolizumab x 4
Chemotherapy
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Immunotherapy
- Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- Surgery, then Pembrolizumab x 9
References
- KEYNOTE-522: Schmid P, Cortes J, Pusztai L, McArthur H, Kümmel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Foukakis T, Fasching PA, Cardoso F, Untch M, Jia L, Karantza V, Zhao J, Aktan G, Dent R, O'Shaughnessy J; KEYNOTE-522 Investigators. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020 Feb 27;382(9):810-821. link to original article contains verified protocol PubMed NCT03036488
nab-Paclitaxel & Atezolizumab
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mittendorf et al. 2020 (IMpassion031) | 2017-2019 | Phase III (E-esc) | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Chemotherapy
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 125 mg/m2 IV once per day on days 1 & 8
Immunotherapy
- Atezolizumab (Tecentriq) 840 mg IV once on day 1
14-day cycle for 6 cycles
Subsequent treatment
- ddAC & Atezolizumab x 4, then Surgery
References
- IMpassion031: Mittendorf EA, Zhang H, Barrios CH, Saji S, Jung KH, Hegg R, Koehler A, Sohn J, Iwata H, Telli ML, Ferrario C, Punie K, Penault-Llorca F, Patel S, Duc AN, Liste-Hermoso M, Maiya V, Molinero L, Chui SY, Harbeck N. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet. 2020 Sep 18:S0140-6736(20)31953-X. Epub ahead of print. link to original article contains verified protocol PubMed NCT03197935
Paclitaxel monotherapy
T: T axol (Paclitaxel)
wP: w eekly P aclitaxel
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sikov et al. 2014 (CALGB 40603) | 2009-2012 | Phase III (C) | Carboplatin & Paclitaxel Carboplatin, Paclitaxel, Bevacizumab Paclitaxel & Bevacizumab | Inferior pCR rate |
Rugo et al. 2016 (I-SPY 2) | 2010-2012 | Adaptively Randomized Phase II (C) | Paclitaxel & VC | Seems to have inferior pCR rate |
Loibl et al. 2018 (BrighTNess) | 2014-2016 | Phase III (C) | 1. Carboplatin & Paclitaxel | Not reported in abstract |
2. CP & Veliparib | Inferior pCR rate |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15, 22
28-day cycle for 3 cycles
Subsequent treatment
- CALGB 40603: ddAC x 4, then surgery
- I-SPY2 & BrighTNess: AC x 4 or ddAC x 4, then surgery
References
- CALGB 40603: Sikov WM, Berry DA, Perou CM, Singh B, Cirrincione CT, Tolaney SM, Kuzma CS, Pluard TJ, Somlo G, Port ER, Golshan M, Bellon JR, Collyar D, Hahn OM, Carey LA, Hudis CA, Winer EP. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J Clin Oncol. 2015 Jan 1;33(1):13-21. Epub 2014 Aug 4. link to original article link to PMC article contains verified protocol PubMed NCT00861705
- I-SPY 2: Rugo HS, Olopade OI, DeMichele A, Yau C, van 't Veer LJ, Buxton MB, Hogarth M, Hylton NM, Paoloni M, Perlmutter J, Symmans WF, Yee D, Chien AJ, Wallace AM, Kaplan HG, Boughey JC, Haddad TC, Albain KS, Liu MC, Isaacs C, Khan QJ, Lang JE, Viscusi RK, Pusztai L, Moulder SL, Chui SY, Kemmer KA, Elias AD, Edmiston KK, Euhus DM, Haley BB, Nanda R, Northfelt DW, Tripathy D, Wood WC, Ewing C, Schwab R, Lyandres J, Davis SE, Hirst GL, Sanil A, Berry DA, Esserman LJ; I-SPY 2 Investigators. Adaptive randomization of veliparib-carboplatin treatment in breast cancer. N Engl J Med. 2016 Jul 7;375(1):23-34. link to original article contains verified protocol link to PMC article PubMed NCT01042379
- BrighTNess: Loibl S, O'Shaughnessy J, Untch M, Sikov WM, Rugo HS, McKee MD, Huober J, Golshan M, von Minckwitz G, Maag D, Sullivan D, Wolmark N, McIntyre K, Ponce Lorenzo JJ, Metzger Filho O, Rastogi P, Symmans WF, Liu X, Geyer CE Jr. Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial. Lancet Oncol. 2018 Apr;19(4):497-509. Epub 2018 Feb 28. link to original article contain protocol PubMed NCT02032277
Neoadjuvant response criteria
Clinical response rate (cRR)
Although fairly dated, some trials such as ACOSOG Z1031 make use of the WHO criteria for response to neoadjuvant therapy. Included here primarily for historical purposes.
References
- Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer. 1981 Jan 1;47(1):207-14. link to original article PubMed
Miller-Payne scoring system
- Grade 1: No change or some changes to individual malignant cells, but no reduction in overall cellularity
- Grade 2: Minor loss of tumor cells (up to 30%), but overall cellularity still high
- Grade 3: An estimated 30 to 90% reduction in the number of tumor cells
- Grade 4: Marked disappearance of tumor cells such that only small clusters or widely dispersed individual cells remain (loss of greater than 90% of tumor cells)
- Grade 5: No invasive cancer cells identifiable in sections from the site of the tumor (carcinoma in situ may be present)
References
- Ogston KN, Miller ID, Payne S, Hutcheon AW, Sarkar TK, Smith I, Schofield A, Heys SD. A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast. 2003 Oct;12(5):320-7. link to original article PubMed
Residual cancer burden (RCB)
- The RCB is calculated as follows: RCB = 1.4 (finv*dprim )0.17 + [4(1 - 0.75 LN )dmet ]0.17
- where dprim is derived from the bidimensional diameters of the primary tumor bed in the resected specimen, finv is the proportion of the primary tumor bed that contains invasive carcinoma, LN is the number of axillary lymph nodes containing metastatic carcinoma, and dmet is the diameter of the largest metastasis in an axillary lymph node.
- The cut-off points are 1.36 and 3.28.
References
- Symmans WF, Peintinger F, Hatzis C, Rajan R, Kuerer H, Valero V, Assad L, Poniecka A, Hennessy B, Green M, Buzdar AU, Singletary SE, Hortobagyi GN, Pusztai L. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol. 2007 Oct 1;25(28):4414-22. Epub 2007 Sep 4. link to original article PubMed
Residual disease in breast and nodes (RDBN)
- Level 1: pCR in breast and nodes with or without in situ carcinoma
- Levels 2 to 4: Residual disease, calculated as 0.2 (residual breast tumor size in cm) + index of involved nodes (0 for no positive nodes, 1 for 1 to 4 positive nodes, 2 for 5 to 7 positive nodes, and 3 for 8 positive nodes) + the Scarff–Bloom–Richardson grade (1, 2, or 3). The cut-off points are 3 and 4.3.
References
- Chollet P, Abrial C, Durando X, Thivat E, Tacca O, Mouret-Reynier MA, Leheurteur M, Kwiatkowski F, Dauplat J, Penault-Llorca F. A new prognostic classification after primary chemotherapy for breast cancer: residual disease in breast and nodes (RDBN). Cancer J. 2008 Mar-Apr;14(2):128-32. link to original article PubMed
Sataloff's classification
- Breast:
- T-A: Total or nearly total therapeutic effect
- T-B: Greater than 50% therapeutic effect
- T-C: Less than 50% therapeutic effect
- T-D: No therapeutic effect
- Lymph node:
- N-A: Therapeutic effect but no metastasis
- N-B: No metastasis, no therapeutic effect
- N-C: Therapeutic effect but metastasis
- N-D: Metastasis, no therapeutic effect
References
- Sataloff DM, Mason BA, Prestipino AJ, Seinige UL, Lieber CP, Baloch Z. Pathologic response to induction chemotherapy in locally advanced carcinoma of the breast: a determinant of outcome. J Am Coll Surg. 1995 Mar;180(3):297-306. PubMed
Tumor response ratio
Calculated as follows: Residual breast disease observed upon pathologic examination divided by the size of the tumor on the pre-neoadjuvant therapy image.
- TRR = 0: pathologic complete response (pCR)
- TRR greater than 0 up to 0.4: strong partial response
- TRR greater than 0.4 up to 1.0: weak partial response (WPR)
- TRR greater than 1.0: tumor growth
References
- Miller M, Ottesen RA, Niland JC, Kruper L, Chen SL, Vito C. Tumor response ratio predicts overall survival in breast cancer patients treated with neoadjuvant chemotherapy. Ann Surg Oncol. 2014 Oct;21(10):3317-23. Epub 2014 Jul 25. link to original article PubMed
ypTNM staging
This system is proprietary to the AJCC. Please visit their site or consult the AJCC Manual for further details.
Adjuvant chemotherapy
Cyclophosphamide & Doxorubicin (AC)
AC: A driamycin (Doxorubicin) & C yclophosphamide
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fisher et al. 1990 (NSABP B-15) | 1984-1988 | Phase III (E-RT-de-esc) | 1. AC, then CMF | Did not meet primary endpoints of DFS/OS |
2. CMF | Did not meet primary endpoints of DFS/OS | |||
Yardley et al. 2017 (TITAN - breast) | 2008-2011 | Non-randomized portion of RCT |
Note: NSABP B-15 was conducted prior to routine testing of HER2, so it technically included "double-negative" patients. TITAN is labeled "TITAN - breast" so as not to confuse it with the trial by the same name in NSCLC.
Preceding treatment
- Surgery
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- TITAN: Ixabepilone versus Paclitaxel
References
- NSABP B-15: Fisher B, Brown AM, Dimitrov NV, Poisson R, Redmond C, Margolese RG, Bowman D, Wolmark N, Wickerham DL, Kardinal CG, Shibata H, Paterson AHG, Sutherland CM, Robert NJ, Ager PJ, Levy L, Wolter J, Wozniak T, Fisher ER, Deutsch M. Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B-15. J Clin Oncol. 1990 Sep;8(9):1483-96. link to original article contains verified protocol PubMed
- Pooled update: Taghian A, Jeong JH, Mamounas E, Anderson S, Bryant J, Deutsch M, Wolmark N. Patterns of locoregional failure in patients with operable breast cancer treated by mastectomy and adjuvant chemotherapy with or without tamoxifen and without radiotherapy: results from five National Surgical Adjuvant Breast and Bowel Project randomized clinical trials. J Clin Oncol. 2004 Nov 1;22(21):4247-54. Epub 2004 Sep 27. link to original article PubMed
- TITAN: Yardley DA, Arrowsmith ER, Daniel BR, Eakle J, Brufsky A, Drosick DR, Kudrik F, Bosserman LD, Keaton MR, Goble SA, Bubis JA, Priego VM, Pendergrass K, Manalo Y, Bury M, Gravenor DS, Rodriguez GI, Inhorn RC, Young RR, Harwin WN, Silver C, Hainsworth JD, Burris HA 3rd. TITAN: phase III study of doxorubicin/cyclophosphamide followed by ixabepilone or paclitaxel in early-stage triple-negative breast cancer. Breast Cancer Res Treat. 2017 Aug;164(3):649-658. Epub 2017 May 15. link to original article contains verified protocol PubMed NCT00789581
Bevacizumab-containing therapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cameron et al. 2013 (BEATRICE) | 2007-2010 | Phase III (E-esc) | Standard adjuvant therapy | Did not meet primary endpoint of IDFS |
This is the negative experimental arm of an important negative trial, so is included here for historical reference purposes, only.
Preceding treatment
- Surgery
Chemotherapy
- Standard chemotherapy (not specified)
Targeted therapy
- Bevacizumab (Avastin)
References
- BEATRICE: Cameron D, Brown J, Dent R, Jackisch C, Mackey J, Pivot X, Steger GG, Suter TM, Toi M, Parmar M, Laeufle R, Im YH, Romieu G, Harvey V, Lipatov O, Pienkowski T, Cottu P, Chan A, Im SA, Hall PS, Bubuteishvili-Pacaud L, Henschel V, Deurloo RJ, Pallaud C, Bell R. Adjuvant bevacizumab-containing therapy in triple-negative breast cancer (BEATRICE): primary results of a randomised, phase 3 trial. Lancet Oncol. 2013 Sep;14(10):933-42. Epub 2013 Aug 7. link to original article PubMed NCT00528567
- Update: Bell R, Brown J, Parmar M, Toi M, Suter T, Steger GG, Pivot X, Mackey J, Jackisch C, Dent R, Hall P, Xu N, Morales L, Provencher L, Hegg R, Vanlemmens L, Kirsch A, Schneeweiss A, Masuda N, Overkamp F, Cameron D. Final efficacy and updated safety results of the randomized phase III BEATRICE trial evaluating adjuvant bevacizumab-containing therapy in triple-negative early breast cancer. Ann Oncol. 2017 Apr 1;28(4):754-760. link to original article PubMed
Capecitabine monotherapy
Regimen variant #1, 1300 mg/m2/day
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wang et al. 2021 (SYSUCC-001) | 2010-2016 | Phase III (E-esc) | Observation | Seems to have superior DFS |
Note: this is a continuous (uninterrupted) dosing schema.
Preceding treatment
- "Standard adjuvant therapy"
Chemotherapy
- Capecitabine (Xeloda) 650 mg/m2 PO twice per day
28-day cycle for 13 cycles (1 year)
Regimen variant #2, 2000 mg/m2/day x 6
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mayer et al. 2021 (ECOG-ACRIN EA1131) | 2015-2021 | Phase III (C) | 1. Carboplatin 2. Cisplatin | Inconclusive whether non-inferior iDFS |
Preceding treatment
- At least one cycle of taxane with or without anthracycline, then surgery
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day
21-day cycle for 6 cycles
Regimen variant #3, 2000 mg/m2/day x 8
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lluch et al. 2019 (GEICAM/2003-11; CIBOMA/2004-01) | 2006-2011 | Phase III (E-esc) | Observation | Did not meet primary endpoint of DFS |
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day
21-day cycle for 8 cycles
Regimen variant #4, 2500 mg/m2/day
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Masuda et al. 2017 (CREATE-X) | 2007-2012 | Phase III (E-esc) | Standard therapy | Superior OS |
Note: All patients in CREATE-X had residual disease at time of surgical resection. Although this trial was not specifically for TNBC, a large number (N=286) of enrolled patients had TNBC, and the survival benefit appeared limited to this group in the subgroup analysis.
Preceding treatment
- Neoadjuvant chemotherapy containing anthracycline, taxane, or both, then surgery
Chemotherapy
- Capecitabine (Xeloda) 1250 mg/m2 PO twice per day on days 1 to 14
21-day cycle for 6 to 8 cycles
References
- CREATE-X: Masuda N, Lee SJ, Ohtani S, Im YH, Lee ES, Yokota I, Kuroi K, Im SA, Park BW, Kim SB, Yanagita Y, Ohno S, Takao S, Aogi K, Iwata H, Jeong J, Kim A, Park KH, Sasano H, Ohashi Y, Toi M. Adjuvant capecitabine for breast cancer after preoperative chemotherapy; Japan Breast Cancer Research Group; Korean Breast Cancer Study Group; Korean Cancer Study Group. N Engl J Med. 2017 Jun 1;376(22):2147-2159. link to original article contains verified protocol PubMed UMIN000000843
- GEICAM/2003-11; CIBOMA/2004-01: Lluch A, Barrios CH, Torrecillas L, Ruiz-Borrego M, Bines J, Segalla J, Guerrero-Zotano Á, García-Sáenz JA, Torres R, de la Haba J, García-Martínez E, Gómez HL, Llombart A, Bofill JS, Baena-Cañada JM, Barnadas A, Calvo L, Pérez-Michel L, Ramos M, Fernández I, Rodríguez-Lescure Á, Cárdenas J, Vinholes J, Martínez de Dueñas E, Godes MJ, Seguí MA, Antón A, López-Álvarez P, Moncayo J, Amorim G, Villar E, Reyes S, Sampaio C, Cardemil B, Escudero MJ, Bezares S, Carrasco E, Martín M; GEICAM Spanish Breast Cancer Group; CIBOMA (Iberoamerican Coalition for Research in Breast Oncology); LACOG (Latin American Cooperative Oncology Group). Phase III Trial of Adjuvant Capecitabine After Standard Neo-/Adjuvant Chemotherapy in Patients With Early Triple-Negative Breast Cancer (GEICAM/2003-11_CIBOMA/2004-01). J Clin Oncol. 2020 Jan 20;38(3):203-213. Epub 2019 Dec 5. Erratum in: J Clin Oncol. 2020 Mar 10;38(8):847. link to original article link to PMC article PubMed NCT00130533
- SYSUCC-001: Wang X, Wang SS, Huang H, Cai L, Zhao L, Peng RJ, Lin Y, Tang J, Zeng J, Zhang LH, Ke YL, Wang XM, Liu XM, Chen QJ, Zhang AQ, Xu F, Bi XW, Huang JJ, Li JB, Pang DM, Xue C, Shi YX, He ZY, Lin HX, An X, Xia W, Cao Y, Guo Y, Su YH, Hua X, Wang XY, Hong RX, Jiang KK, Song CG, Huang ZZ, Shi W, Zhong YY, Yuan ZY; South China Breast Cancer Group (SCBCG). Effect of Capecitabine Maintenance Therapy Using Lower Dosage and Higher Frequency vs Observation on Disease-Free Survival Among Patients With Early-Stage Triple-Negative Breast Cancer Who Had Received Standard Treatment: The SYSUCC-001 Randomized Clinical Trial. JAMA. 2021 Jan 5;325(1):50-58. link to original article contains protocol link to PMC article PubMed NCT01112826
- ECOG-ACRIN EA1131: Mayer IA, Zhao F, Arteaga CL, Symmans WF, Park BH, Burnette BL, Tevaarwerk AJ, Garcia SF, Smith KL, Makower DF, Block M, Morley KA, Jani CR, Mescher C, Dewani SJ, Tawfik B, Flaum LE, Mayer EL, Sikov WM, Rodler ET, Wagner LI, DeMichele AM, Sparano JA, Wolff AC, Miller KD. Randomized Phase III Postoperative Trial of Platinum-Based Chemotherapy Versus Capecitabine in Patients With Residual Triple-Negative Breast Cancer Following Neoadjuvant Chemotherapy: ECOG-ACRIN EA1131. J Clin Oncol. 2021 Aug 10;39(23):2539-2551. Epub 2021 Jun 6. link to original article contains verified protocol PubMed NCT02445391
- SASCIA: NCT04595565
Capecitabine & Docetaxel (TX)
TX: T axotere (Docetaxel) & X eloda (Capecitabine)
XT: X eloda (Capecitabine) & T axotere (Docetaxel)
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Li et al. 2020 (CBCSG010) | 2012-2013 | Phase III (E-esc) | Docetaxel | Seems to have superior DFS |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Surgery
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
- XEC x 3
References
- CBCSG010: Li J, Yu K, Pang D, Wang C, Jiang J, Yang S, Liu Y, Fu P, Sheng Y, Zhang G, Cao Y, He Q, Cui S, Wang X, Ren G, Li X, Yu S, Liu P, Qu X, Tang J, Wang O, Fan Z, Jiang G, Zhang J, Wang J, Zhang H, Wang S, Zhang J, Jin F, Rao N, Ma B, He P, Xu B, Zhuang Z, Wang J, Sun Q, Guo X, Mo M, Shao Z; CBCSG010 Study Group. Adjuvant Capecitabine With Docetaxel and Cyclophosphamide Plus Epirubicin for Triple-Negative Breast Cancer (CBCSG010): An Open-Label, Randomized, Multicenter, Phase III Trial. J Clin Oncol. 2020 Jun 1;38(16):1774-1784. Epub 2020 Apr 10. link to original article contains verified protocol link to PMC article PubMed NCT01642771
Carboplatin & Paclitaxel (CP)
PCb: P aclitaxel & C ar b oplatin
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yu et al. 2020 (PATTERN) | 2011-2016 | Phase III (E-esc) | FEC-D | Seems to have superior DFS |
Preceding treatment
- Surgery
Chemotherapy
- Carboplatin (Paraplatin) AUC 2 IV once per day on days 1, 8, 15
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
28-day cycle for 6 cycles
References
- PATTERN: Yu KD, Ye FG, He M, Fan L, Ma D, Mo M, Wu J, Liu GY, Di GH, Zeng XH, He PQ, Wu KJ, Hou YF, Wang J, Wang C, Zhuang ZG, Song CG, Lin XY, Toss A, Ricci F, Shen ZZ, Shao ZM. Effect of Adjuvant Paclitaxel and Carboplatin on Survival in Women With Triple-Negative Breast Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Sep 1;6(9):1390-1396. link to original article link to PMC article contains protocol PubMed NCT01216111
CMF
CMF: C yclophosphamide, M ethotrexate, F luorouracil
Regimen variant #1, 1000/50/2000
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ploner et al. 2003 (ABCSG 3) | 1984-NR | Phase III (C) | AV-CMF | Did not meet endpoints of DFS/OS |
Note: this trial was conducted prior to routine testing of HER2, so it technically included "double-negative" patients.
Preceding treatment
- Surgery
Chemotherapy
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once per day on days 1 & 8
- Methotrexate (MTX) 25 mg/m2 IV once per day on days 1 & 8
- Fluorouracil (5-FU) 1000 mg/m2 IV once per day on days 1 & 8
28-day cycle for 6 cycles
Regimen variant #2, 1400/80/1200
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fisher et al. 1990 (NSABP B-15) | 1984-1988 | Phase III (C) | 1. AC | Did not meet primary endpoints of DFS/OS |
2. AC, then CMF | Did not meet primary endpoints of DFS/OS |
Note: this trial was conducted prior to routine testing of HER2, so it technically included "double-negative" patients.
Preceding treatment
- Surgery
Chemotherapy
- Cyclophosphamide (Cytoxan) 100 mg/m2 PO once per day on days 1 to 14
- Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
- Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1 & 8
28-day cycle for 6 cycles
References
- NSABP B-15: Fisher B, Brown AM, Dimitrov NV, Poisson R, Redmond C, Margolese RG, Bowman D, Wolmark N, Wickerham DL, Kardinal CG, Shibata H, Paterson AHG, Sutherland CM, Robert NJ, Ager PJ, Levy L, Wolter J, Wozniak T, Fisher ER, Deutsch M. Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B-15. J Clin Oncol. 1990 Sep;8(9):1483-96. link to original article contains verified protocol PubMed
- ABCSG 3: Ploner F, Jakesz R, Hausmaninger H, Kolb R, Stierer M, Fridrik M, Steindorfer P, Gnant M, Haider K, Mlineritsch B, Tschurtschenthaler G, Steger G, Seifert M, Kubista E, Samonigg H; ABCSG. Randomised trial: One cycle of anthracycline-containing adjuvant chemotherapy compared with six cycles of CMF treatment in node-positive, hormone receptor-negative breast cancer patients. Onkologie. 2003 Apr;26(2):115-9. link to original article contains verified protocol PubMed
Docetaxel monotherapy
T: T axotere (Docetaxel)
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Li et al. 2020 (CBCSG010) | 2012-2013 | Phase III (C) | XT | Seems to have inferior DFS |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Surgery
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
- FEC x 3
References
- CBCSG010: Li J, Yu K, Pang D, Wang C, Jiang J, Yang S, Liu Y, Fu P, Sheng Y, Zhang G, Cao Y, He Q, Cui S, Wang X, Ren G, Li X, Yu S, Liu P, Qu X, Tang J, Wang O, Fan Z, Jiang G, Zhang J, Wang J, Zhang H, Wang S, Zhang J, Jin F, Rao N, Ma B, He P, Xu B, Zhuang Z, Wang J, Sun Q, Guo X, Mo M, Shao Z; CBCSG010 Study Group. Adjuvant Capecitabine With Docetaxel and Cyclophosphamide Plus Epirubicin for Triple-Negative Breast Cancer (CBCSG010): An Open-Label, Randomized, Multicenter, Phase III Trial. J Clin Oncol. 2020 Jun 1;38(16):1774-1784. Epub 2020 Apr 10. link to original article contains verified protocol link to PMC article PubMed
FAC
FAC: F luorouracil, A driamycin (Doxorubicin), C yclophosphamide
CAF: C yclophosphamide, A driamycin (Doxorubicin), F luorouracil
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fetting et al. 1998 (INT-0108) | 1989-1993 | Phase III (C) | FAC x 16 weeks | Did not meet primary endpoints of RFS60/OS60 |
Preceding treatment
- Surgery
Chemotherapy
- Fluorouracil (5-FU)
- Doxorubicin (Adriamycin)
- Cyclophosphamide (Cytoxan)
21-day cycle for 6 cycles
References
- INT-0108: Fetting JH, Gray R, Fairclough DL, Smith TJ, Margolin KA, Citron ML, Grove-Conrad M, Cella D, Pandya K, Robert N, Henderson IC, Osborne CK, Abeloff MD; ECOG; CALGB. Sixteen-week multidrug regimen versus cyclophosphamide, doxorubicin, and fluorouracil as adjuvant therapy for node-positive, receptor-negative breast cancer: an Intergroup study. J Clin Oncol. 1998 Jul;16(7):2382-91. link to original article PubMed
FEC
FEC: F luorouracil, E pirubicin, C yclophosphamide
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Li et al. 2020 (CBCSG010) | 2012-2013 | Phase III (C) | XEC | Seems to have inferior DFS |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Surgery, then T x 3
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
21-day cycle for 3 cycles
References
- CBCSG010: Li J, Yu K, Pang D, Wang C, Jiang J, Yang S, Liu Y, Fu P, Sheng Y, Zhang G, Cao Y, He Q, Cui S, Wang X, Ren G, Li X, Yu S, Liu P, Qu X, Tang J, Wang O, Fan Z, Jiang G, Zhang J, Wang J, Zhang H, Wang S, Zhang J, Jin F, Rao N, Ma B, He P, Xu B, Zhuang Z, Wang J, Sun Q, Guo X, Mo M, Shao Z; CBCSG010 Study Group. Adjuvant Capecitabine With Docetaxel and Cyclophosphamide Plus Epirubicin for Triple-Negative Breast Cancer (CBCSG010): An Open-Label, Randomized, Multicenter, Phase III Trial. J Clin Oncol. 2020 Jun 1;38(16):1774-1784. Epub 2020 Apr 10. link to original article contains verified protocol link to PMC article PubMed
Pembrolizumab monotherapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Schmid et al. 2020 (KEYNOTE-522) | 2017-2018 | Phase III (E-RT-esc) | Placebo | Superior pCR rate |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Surgery
Immunotherapy
- Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycle for up to 9 cycles
References
- KEYNOTE-522: Schmid P, Cortes J, Pusztai L, McArthur H, Kümmel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Foukakis T, Fasching PA, Cardoso F, Untch M, Jia L, Karantza V, Zhao J, Aktan G, Dent R, O'Shaughnessy J; KEYNOTE-522 Investigators. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020 Feb 27;382(9):810-821. link to original article contains verified protocol PubMed NCT03036488
T-AC (Paclitaxel)
T-AC: T axol (Paclitaxel) followed by A driamycin (Doxorubicin) & C yclophosphamide
Protocol
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
In progress (ALEXANDRA) | 2018-ongoing | Phase III (C) | 1. T-AC & Atezolizumab 2. T-EC & Atezolizumab | In progress |
Note: Dosing information is from ASCO 2021 Abstract TPS597.
Preceding treatment
- Surgery
Chemotherapy, part 1
- Paclitaxel (Taxol) 80 mg/m2 IV once on day 1
7-day cycle for 12 cycles
Chemotherapy, part 2
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
14-day cycle for 4 cycles
References
- ALEXANDRA: NCT03498716
T-EC (Paclitaxel)
T-EC: T axol (Paclitaxel) followed by E pirubicin & C yclophosphamide
Protocol
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
In progress (ALEXANDRA) | 2018-ongoing | Phase III (C) | 1. T-AC & Atezolizumab 2. T-EC & Atezolizumab | In progress |
Note: Dosing information is from ASCO 2021 Abstract TPS597.
Preceding treatment
- Surgery
Chemotherapy, part 1
- Paclitaxel (Taxol) 80 mg/m2 IV once on day 1
7-day cycle for 12 cycles
Chemotherapy, part 2
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
14-day cycle for 4 cycles
References
- ALEXANDRA: NCT03498716
XEC
XEC: X eloda (Capecitabine), E pirubicin, C yclophosphamide
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Li et al. 2020 (CBCSG010) | 2012-2013 | Phase III (E-switch-ic) | FEC | Seems to have superior DFS |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Surgery, then XT x 3
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for 3 cycles
References
- CBCSG010: Li J, Yu K, Pang D, Wang C, Jiang J, Yang S, Liu Y, Fu P, Sheng Y, Zhang G, Cao Y, He Q, Cui S, Wang X, Ren G, Li X, Yu S, Liu P, Qu X, Tang J, Wang O, Fan Z, Jiang G, Zhang J, Wang J, Zhang H, Wang S, Zhang J, Jin F, Rao N, Ma B, He P, Xu B, Zhuang Z, Wang J, Sun Q, Guo X, Mo M, Shao Z; CBCSG010 Study Group. Adjuvant Capecitabine With Docetaxel and Cyclophosphamide Plus Epirubicin for Triple-Negative Breast Cancer (CBCSG010): An Open-Label, Randomized, Multicenter, Phase III Trial. J Clin Oncol. 2020 Jun 1;38(16):1774-1784. Epub 2020 Apr 10. link to original article contains verified protocol link to PMC article PubMed
Metastatic disease, first-line therapy
Carboplatin & Gemcitabine (GCb)
GCb: G emcitabine & C ar b oplatin
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
O'Shaughnessy et al. 2011 (TCD11485) | 2007-2009 | Randomized Phase II (C) | GCb & Iniparib | Inferior OS |
O'Shaughnessy et al. 2014 (EFC11486) | 2009-2010 | Phase III (C) | GCb & Iniparib | Might have inferior PFS |
Cortes et al. 2020 (KEYNOTE-355) | 2017-2018 | Phase III (C) | Investigator's choice of: 1. GCb & Pembrolizumab 2. Paclitaxel & Pembrolizumab 3. nab-Paclitaxel & Pembrolizumab | Inferior PFS1 |
1Reported efficacy for KEYNOTE-355 is for patients with CPS of 10 or more.
Chemotherapy
- Carboplatin (Paraplatin) AUC 2 IV once per day on days 1 & 8
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycles
References
- TCD11485: O'Shaughnessy J, Osborne C, Pippen JE, Yoffe M, Patt D, Rocha C, Koo IC, Sherman BM, Bradley C. Iniparib plus chemotherapy in metastatic triple-negative breast cancer. N Engl J Med. 2011 Jan 20;364(3):205-14. Epub 2011 Jan 5. link to original article contains protocol PubMed NCT00540358
- EFC11486: O'Shaughnessy J, Schwartzberg L, Danso MA, Miller KD, Rugo HS, Neubauer M, Robert N, Hellerstedt B, Saleh M, Richards P, Specht JM, Yardley DA, Carlson RW, Finn RS, Charpentier E, Garcia-Ribas I, Winer EP. Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer. J Clin Oncol. 2014 Dec 1;32(34):3840-7. Epub 2014 Oct 27. link to original article contains protocol PubMed NCT00938652
- KEYNOTE-355: Cortes J, Cescon DW, Rugo HS, Nowecki Z, Im SA, Yusof MM, Gallardo C, Lipatov O, Barrios CH, Holgado E, Iwata H, Masuda N, Otero MT, Gokmen E, Loi S, Guo Z, Zhao J, Aktan G, Karantza V, Schmid P; KEYNOTE-355 Investigators. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020 Dec 5;396(10265):1817-1828. link to original article contains verified protocol PubMed NCT02819518
- PRESERVE 2: EudraCT 2020-004930-39
Carboplatin & Gemcitabine (GCb) & Pembrolizumab
GCb & Pembrolizumab: G emcitabine, C ar b oplatin, Pembrolizumab
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cortes et al. 2020 (KEYNOTE-355) | 2017-2018 | Phase III (E-RT-esc) | Investigator's choice of: 1. GCb 2. Paclitaxel 3. nab-Paclitaxel | Superior PFS1 (HR 0.6, 95% CI 0.49-0.86) |
1Reported efficacy is in the group with CPS of 10 or more.
Chemotherapy
- Carboplatin (Paraplatin) AUC 2 IV once per day on days 1 & 8
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
Immunotherapy
- Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycle for up to 35 cycles (2 years)
References
- KEYNOTE-355: Cortes J, Cescon DW, Rugo HS, Nowecki Z, Im SA, Yusof MM, Gallardo C, Lipatov O, Barrios CH, Holgado E, Iwata H, Masuda N, Otero MT, Gokmen E, Loi S, Guo Z, Zhao J, Aktan G, Karantza V, Schmid P; KEYNOTE-355 Investigators. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020 Dec 5;396(10265):1817-1828. link to original article contains verified protocol PubMed NCT02819518
Cisplatin & Docetaxel (DC)
TP: T axotere (Docetaxel) & P latinol (Cisplatin)
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fan et al. 2012 | NR | Phase III (E-switch-ic) | TX (Taxotere) | Seems to have superior OS |
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
21-day cycle for up to 6 cycles
References
- Fan Y, Xu BH, Yuan P, Ma F, Wang JY, Ding XY, Zhang P, Li Q, Cai RG. Docetaxel-cisplatin might be superior to docetaxel-capecitabine in the first-line treatment of metastatic triple-negative breast cancer. Ann Oncol. 2013 May;24(5):1219-25. Epub 2012 Dec 5. link to original article contains protocol PubMed
Cisplatin & Gemcitabine (GC)
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hu et al. 2015 (CBCSG006) | 2011-2013 | Phase III (E-switch-ic) | Gemcitabine & Paclitaxel | Superior PFS |
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Gemcitabine (Gemzar) 1250 mg/m2 IV once per day on days 1 & 8
21-day cycle for up to 8 cycles
References
- CBCSG006: Hu XC, Zhang J, Xu BH, Cai L, Ragaz J, Wang ZH, Wang BY, Teng YE, Tong ZS, Pan YY, Yin YM, Wu CP, Jiang ZF, Wang XJ, Lou GY, Liu DG, Feng JF, Luo JF, Sun K, Gu YJ, Wu J, Shao ZM. Cisplatin plus gemcitabine versus paclitaxel plus gemcitabine as first-line therapy for metastatic triple-negative breast cancer (CBCSG006): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2015 Apr;16(4):436-46. Epub 2015 Mar 18. link to original article contains protocol PubMed NCT01287624
Docetaxel monotherapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tutt et al. 2018 (TNT) | 2008-2014 | Phase III (C) | Carboplatin | Did not meet primary endpoint of ORR |
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
21-day cycle for 6 cycles
References
- TNT: Tutt A, Tovey H, Cheang MCU, Kernaghan S, Kilburn L, Gazinska P, Owen J, Abraham J, Barrett S, Barrett-Lee P, Brown R, Chan S, Dowsett M, Flanagan JM, Fox L, Grigoriadis A, Gutin A, Harper-Wynne C, Hatton MQ, Hoadley KA, Parikh J, Parker P, Perou CM, Roylance R, Shah V, Shaw A, Smith IE, Timms KM, Wardley AM, Wilson G, Gillett C, Lanchbury JS, Ashworth A, Rahman N, Harries M, Ellis P, Pinder SE, Bliss JM. Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial. Nat Med. 2018 May;24(5):628-637. Epub 2018 Apr 30. link to original article link to PMC article PubMed NCT00532727
FAC
FAC: F luorouracil, A driamycin (Doxorubicin), C yclophosphamide
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pandya et al. 2007 (ECOG E3185) | 1987-1991 | Phase III (C) | CAF/TsAVbH | Did not meet primary endpoint of TTF |
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 & 8
- Doxorubicin (Adriamycin) 30 mg/m2 IV once per day on days 1 & 8
- Cyclophosphamide (Cytoxan) 100 mg/m2 PO once per day on days 1 to 14
28-day cycle for up to 6 cycles
References
- ECOG E3185: Pandya KJ, Hu P, Osborne CK, Falkson G, Tormey DC; ECOG. Phase III study of standard combination versus rotating regimen of induction chemotherapy in patients with hormone insensitive metastatic breast cancer: an Eastern Cooperative Oncology Group Intergroup Study (E3185). Am J Clin Oncol. 2007 Apr;30(2):113-25. link to original article contains verified protocol PubMed
Paclitaxel monotherapy
Regimen variant #1, 80 mg/m2
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kim et al. 2017 (LOTUS) | 2014-2016 | Randomized Phase II (C) | Ipatasertib & Paclitaxel | Seems to have inferior PFS |
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
Regimen variant #2, 90 mg/m2
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cortes et al. 2020 (KEYNOTE-355) | 2017-2018 | Phase III (C) | Investigator's choice of: 1. GCb & Pembrolizumab 2. Paclitaxel & Pembrolizumab 3. nab-Paclitaxel & Pembrolizumab | Inferior PFS1 |
Miles et al. 2021 (IMpassion131) | 2017-NR in abstract | Phase III (C) | Paclitaxel & Atezolizumab | Did not meet primary endpoint of PFS |
1Reported efficacy for KEYNOTE-355 is for patients with CPS of 10 or more.
Chemotherapy
- Paclitaxel (Taxol) 90 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
References
- LOTUS: Kim SB, Dent R, Im SA, Espié M, Blau S, Tan AR, Isakoff SJ, Oliveira M, Saura C, Wongchenko MJ, Kapp AV, Chan WY, Singel SM, Maslyar DJ, Baselga J; LOTUS investigators. Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2017 Oct;18(10):1360-1372. Epub 2017 Aug 8. link to original article PubMed NCT02162719
- KEYNOTE-355: Cortes J, Cescon DW, Rugo HS, Nowecki Z, Im SA, Yusof MM, Gallardo C, Lipatov O, Barrios CH, Holgado E, Iwata H, Masuda N, Otero MT, Gokmen E, Loi S, Guo Z, Zhao J, Aktan G, Karantza V, Schmid P; KEYNOTE-355 Investigators. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020 Dec 5;396(10265):1817-1828. link to original article contains verified protocol PubMed NCT02819518
- IMpassion131: Miles D, Gligorov J, André F, Cameron D, Schneeweiss A, Barrios C, Xu B, Wardley A, Kaen D, Andrade L, Semiglazov V, Reinisch M, Patel S, Patre M, Morales L, Patel SL, Kaul M, Barata T, O'Shaughnessy J; IMpassion131 investigators. Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Ann Oncol. 2021 Aug;32(8):994-1004. Epub 2021 Jul 1. link to original article contains protocol PubMed NCT03125902
Paclitaxel & Pembrolizumab
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cortes et al. 2020 (KEYNOTE-355) | 2017-2018 | Phase III (E-RT-esc) | Investigator's choice of: 1. Carboplatin & Gemcitabine 2. Paclitaxel 3. nab-Paclitaxel | Superior PFS1 (HR 0.6, 95% CI 0.49-0.86) |
1Reported efficacy is in the group with CPS of 10 or more.
Note: the duration of chemotherapy and immunotherapy cycles is different.
Chemotherapy
- Paclitaxel (Taxol) 90 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
Immunotherapy
- Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycle for up to 35 cycles (2 years)
References
- KEYNOTE-355: Cortes J, Cescon DW, Rugo HS, Nowecki Z, Im SA, Yusof MM, Gallardo C, Lipatov O, Barrios CH, Holgado E, Iwata H, Masuda N, Otero MT, Gokmen E, Loi S, Guo Z, Zhao J, Aktan G, Karantza V, Schmid P; KEYNOTE-355 Investigators. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020 Dec 5;396(10265):1817-1828. link to original article contains verified protocol PubMed NCT02819518
nab-Paclitaxel monotherapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Schmid et al. 2018 (IMpassion130) | 2015-2017 | Phase III (C) | nab-Paclitaxel & Atezolizumab | Might have inferior OS |
Cortes et al. 2020 (KEYNOTE-355) | 2017-2018 | Phase III (C) | Investigator's choice of: 1. GCb & Pembrolizumab 2. Paclitaxel & Pembrolizumab 3. nab-Paclitaxel & Pembrolizumab | Inferior PFS1 |
1Reported efficacy for KEYNOTE-355 is for patients with CPS of 10 or more.
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.
Chemotherapy
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 100 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
References
- IMpassion130: Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, Diéras V, Hegg R, Im SA, Shaw Wright G, Henschel V, Molinero L, Chui SY, Funke R, Husain A, Winer EP, Loi S, Emens LA; IMpassion130 Trial Investigators. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018 Nov 29;379(22):2108-2121. Epub 2018 Oct 20. link to original article contains verified protocol PubMed NCT02425891
- Update: Schmid P, Rugo HS, Adams S, Schneeweiss A, Barrios CH, Iwata H, Diéras V, Henschel V, Molinero L, Chui SY, Maiya V, Husain A, Winer EP, Loi S, Emens LA; IMpassion130 Investigators. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 Jan;21(1):44-59. Epub 2019 Nov 27. link to original article PubMed
- KEYNOTE-355: Cortes J, Cescon DW, Rugo HS, Nowecki Z, Im SA, Yusof MM, Gallardo C, Lipatov O, Barrios CH, Holgado E, Iwata H, Masuda N, Otero MT, Gokmen E, Loi S, Guo Z, Zhao J, Aktan G, Karantza V, Schmid P; KEYNOTE-355 Investigators. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020 Dec 5;396(10265):1817-1828. link to original article contains verified protocol PubMed NCT02819518
nab-Paclitaxel & Atezolizumab
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Schmid et al. 2018 (IMpassion130) | 2015-2017 | Phase III (E-RT-esc) | nab-Paclitaxel | Might have superior OS |
Chemotherapy
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 100 mg/m2 IV once per day on days 1, 8, 15
Immunotherapy
- Atezolizumab (Tecentriq) 840 mg IV once per day on days 1 & 15
28-day cycles
References
- IMpassion130: Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, Diéras V, Hegg R, Im SA, Shaw Wright G, Henschel V, Molinero L, Chui SY, Funke R, Husain A, Winer EP, Loi S, Emens LA; IMpassion130 Trial Investigators. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018 Nov 29;379(22):2108-2121. Epub 2018 Oct 20. link to original article contains verified protocol PubMed NCT02425891
- Update: Schmid P, Rugo HS, Adams S, Schneeweiss A, Barrios CH, Iwata H, Diéras V, Henschel V, Molinero L, Chui SY, Maiya V, Husain A, Winer EP, Loi S, Emens LA; IMpassion130 Investigators. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 Jan;21(1):44-59. Epub 2019 Nov 27. link to original article PubMed
nab-Paclitaxel & Pembrolizumab
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cortes et al. 2020 (KEYNOTE-355) | 2017-2018 | Phase III (E-RT-esc) | Investigator's choice of: 1. Carboplatin & Gemcitabine 2. Paclitaxel 3. nab-Paclitaxel | Superior PFS1 (HR 0.6, 95% CI 0.49-0.86) |
1Reported efficacy is for patients with CPS of 10 or more.
Note: the duration of chemotherapy and immunotherapy cycles is different.
Chemotherapy
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 100 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
Immunotherapy
- Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycle for up to 35 cycles (2 years)
References
- KEYNOTE-355: Cortes J, Cescon DW, Rugo HS, Nowecki Z, Im SA, Yusof MM, Gallardo C, Lipatov O, Barrios CH, Holgado E, Iwata H, Masuda N, Otero MT, Gokmen E, Loi S, Guo Z, Zhao J, Aktan G, Karantza V, Schmid P; KEYNOTE-355 Investigators. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020 Dec 5;396(10265):1817-1828. link to original article contains verified protocol PubMed NCT02819518
Metastatic disease, subsequent lines of therapy
Capecitabine monotherapy
Regimen variant #1, 2000 mg/m2/day
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Thomas et al. 2007 (CA163-046) | 2003-2006 | Phase III (C) | Capecitabine & Ixabepilone | Inferior PFS |
Sparano et al. 2010 (CA163-048) | 2003-2006 | Phase III (C) | Capecitabine & Ixabepilone | Inferior PFS |
Winer et al. 2021 (KEYNOTE-119) | 2015-2017 | Phase III (C) | Pembrolizumab | Did not meet primary endpoint of OS |
Bardia et al. 2021 (ASCENT) | 2017-2019 | Phase III (C) | Sacituzumab govitecan | Inferior OS |
Note: 25% of the patients in CA163-046 had TNBC. KEYNOTE-119 did not specify capecitabine dosing, which was left to the local standard of care. This is the lower bound of dosing specified in ASCENT.
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
21-day cycles
Regimen variant #2, 2500 mg/m2/day
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bardia et al. 2021 (ASCENT) | 2017-2019 | Phase III (C) | Sacituzumab govitecan | Inferior OS |
Note: This is the upper bound of dosing specified in ASCENT.
Chemotherapy
- Capecitabine (Xeloda) 1250 mg/m2 PO twice per day on days 1 to 14
21-day cycles
References
- CA163-046: Thomas ES, Gomez HL, Li RK, Chung HC, Fein LE, Chan VF, Jassem J, Pivot XB, Klimovsky JV, de Mendoza FH, Xu B, Campone M, Lerzo GL, Peck RA, Mukhopadhyay P, Vahdat LT, Roché HH. Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment. J Clin Oncol. 2007 Nov 20;25(33):5210-7. link to original article contains verified protocol PubMed NCT00080301
- Update: Hortobagyi GN, Gomez HL, Li RK, Chung HC, Fein LE, Chan VF, Jassem J, Lerzo GL, Pivot XB, Hurtado de Mendoza F, Xu B, Vahdat LT, Peck RA, Mukhopadhyay P, Roché HH. Analysis of overall survival from a phase III study of ixabepilone plus capecitabine versus capecitabine in patients with MBC resistant to anthracyclines and taxanes. Breast Cancer Res Treat. 2010 Jul;122(2):409-18. Epub 2010 May 8. link to original article PubMed
- Pooled subgroup analysis: Rugo HS, Roche H, Thomas E, Chung HC, Lerzo GL, Vasyutin I, Patel A, Vahdat L. Efficacy and safety of ixabepilone and capecitabine in patients with advanced triple-negative breast cancer: a pooled analysis from two large phase III, randomized clinical trials. Clin Breast Cancer. 2018 Dec;18(6):489-497. Epub 2018 Aug 4. link to original article PubMed
- CA163-048: Sparano JA, Vrdoljak E, Rixe O, Xu B, Manikhas A, Medina C, Da Costa SC, Ro J, Rubio G, Rondinon M, Perez Manga G, Peck R, Poulart V, Conte P. Randomized phase III trial of ixabepilone plus capecitabine versus capecitabine in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2010 Jul 10;28(20):3256-63. link to original article contains verified protocol link to PMC article PubMed NCT00082433
- Pooled subgroup analysis: Rugo HS, Roche H, Thomas E, Chung HC, Lerzo GL, Vasyutin I, Patel A, Vahdat L. Efficacy and safety of ixabepilone and capecitabine in patients with advanced triple-negative breast cancer: a pooled analysis from two large phase III, randomized clinical trials. Clin Breast Cancer. 2018 Dec;18(6):489-497. Epub 2018 Aug 4. link to original article PubMed
- KEYNOTE-119: Winer EP, Lipatov O, Im SA, Goncalves A, Muñoz-Couselo E, Lee KS, Schmid P, Tamura K, Testa L, Witzel I, Ohtani S, Turner N, Zambelli S, Harbeck N, Andre F, Dent R, Zhou X, Karantza V, Mejia J, Cortes J; KEYNOTE-119 investigators. Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Apr;22(4):499-511. Epub 2021 Mar 4. link to original article does not contain protocol PubMed NCT02555657
- ASCENT: Bardia A, Hurvitz SA, Tolaney SM, Loirat D, Punie K, Oliveira M, Brufsky A, Sardesai SD, Kalinsky K, Zelnak AB, Weaver R, Traina T, Dalenc F, Aftimos P, Lynce F, Diab S, Cortés J, O'Shaughnessy J, Diéras V, Ferrario C, Schmid P, Carey LA, Gianni L, Piccart MJ, Loibl S, Goldenberg DM, Hong Q, Olivo MS, Itri LM, Rugo HS; ASCENT Clinical Trial Investigators. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med. 2021 Apr 22;384(16):1529-1541. link to original article contains verified protocol PubMed NCT02574455
Capecitabine & Ixabepilone
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Thomas et al. 2007 (CA163-046) | 2003-2006 | Phase III (E-esc) | Capecitabine | Superior PFS |
Sparano et al. 2010 (CA163-048) | 2003-2006 | Phase III (E-esc) | Capecitabine | Superior PFS |
Note: 25% of the patients in CA163-046 had TNBC.
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
- Ixabepilone (Ixempra) 40 mg/m2 IV once on day 1
21-day cycles
References
- CA163-046: Thomas ES, Gomez HL, Li RK, Chung HC, Fein LE, Chan VF, Jassem J, Pivot XB, Klimovsky JV, de Mendoza FH, Xu B, Campone M, Lerzo GL, Peck RA, Mukhopadhyay P, Vahdat LT, Roché HH. Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment. J Clin Oncol. 2007 Nov 20;25(33):5210-7. link to original article contains verified protocol PubMed NCT00080301
- Update: Hortobagyi GN, Gomez HL, Li RK, Chung HC, Fein LE, Chan VF, Jassem J, Lerzo GL, Pivot XB, Hurtado de Mendoza F, Xu B, Vahdat LT, Peck RA, Mukhopadhyay P, Roché HH. Analysis of overall survival from a phase III study of ixabepilone plus capecitabine versus capecitabine in patients with MBC resistant to anthracyclines and taxanes. Breast Cancer Res Treat. 2010 Jul;122(2):409-18. Epub 2010 May 8. link to original article PubMed
- Pooled subgroup analysis: Rugo HS, Roche H, Thomas E, Chung HC, Lerzo GL, Vasyutin I, Patel A, Vahdat L. Efficacy and safety of ixabepilone and capecitabine in patients with advanced triple-negative breast cancer: a pooled analysis from two large phase III, randomized clinical trials. Clin Breast Cancer. 2018 Dec;18(6):489-497. Epub 2018 Aug 4. link to original article PubMed
- CA163-048: Sparano JA, Vrdoljak E, Rixe O, Xu B, Manikhas A, Medina C, Da Costa SC, Ro J, Rubio G, Rondinon M, Perez Manga G, Peck R, Poulart V, Conte P. Randomized phase III trial of ixabepilone plus capecitabine versus capecitabine in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2010 Jul 10;28(20):3256-63. link to original article contains verified protocol link to PMC article PubMed NCT00082433
- Pooled subgroup analysis: Rugo HS, Roche H, Thomas E, Chung HC, Lerzo GL, Vasyutin I, Patel A, Vahdat L. Efficacy and safety of ixabepilone and capecitabine in patients with advanced triple-negative breast cancer: a pooled analysis from two large phase III, randomized clinical trials. Clin Breast Cancer. 2018 Dec;18(6):489-497. Epub 2018 Aug 4. link to original article PubMed
Carboplatin & Gemcitabine (GCb)
GCb: G emcitabine & C ar b oplatin
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
O'Shaughnessy et al. 2014 (EFC11486) | 2009-2010 | Phase III (C) | GCb & Iniparib | Might have inferior PFS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 2 IV once per day on days 1 & 8
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycles
References
- EFC11486: O'Shaughnessy J, Schwartzberg L, Danso MA, Miller KD, Rugo HS, Neubauer M, Robert N, Hellerstedt B, Saleh M, Richards P, Specht JM, Yardley DA, Carlson RW, Finn RS, Charpentier E, Garcia-Ribas I, Winer EP. Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer. J Clin Oncol. 2014 Dec 1;32(34):3840-7. Epub 2014 Oct 27. link to original article contains protocol PubMed NCT00938652
Enzalutamide monotherapy
Regimen
Study | Years of enrollment | Evidence | Efficacy |
---|---|---|---|
Traina et al. 2018 (MDV3100-11) | 2013-2014 | Phase II | CBR @ 16 wks: 25% (95% CI 17-33) |
Patients had AR-positive TNBC.
Endocrine therapy
- Enzalutamide (Xtandi) 160 mg PO once per day
Continued indefinitely
References
- MDV3100-11: Traina TA, Miller K, Yardley DA, Eakle J, Schwartzberg LS, O'Shaughnessy J, Gradishar W, Schmid P, Winer E, Kelly C, Nanda R, Gucalp A, Awada A, Garcia-Estevez L, Trudeau ME, Steinberg J, Uppal H, Tudor IC, Peterson A, Cortes J. Enzalutamide for the treatment of androgen receptor-expressing triple-negative breast cancer. J Clin Oncol. 2018 Mar 20;36(9):884-890. Epub 2018 Jan 26. link to original article contains verified protocol PubMed NCT01889238
Eribulin monotherapy
Regimen variant #1, 1.23 mg/m2
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bardia et al. 2021 (ASCENT) | 2017-2019 | Phase III (C) | Sacituzumab govitecan | Inferior OS |
Note: This is the European dosing in ASCENT.
Chemotherapy
- Eribulin (Halaven) 1.23 mg/m2 IV once per day on days 1 & 8
21-day cycles
Regimen variant #2, 1.4 mg/m2
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cortes et al. 2011 (EMBRACE) | 2006-2008 | Phase III (E-RT-switch-ic) | Investigator's choice | Seems to have superior OS |
Kaufman et al. 2015 (E7389-G000-301) | 2006-2009 | Phase III (E-switch-ic) | Capecitabine | Might have superior OS |
Winer et al. 2021 (KEYNOTE-119) | 2015-2017 | Phase III (C) | Pembrolizumab | Did not meet primary endpoint of OS |
Bardia et al. 2021 (ASCENT) | 2017-2019 | Phase III (C) | Sacituzumab govitecan | Inferior OS |
Note: in EMBRACE, 144 patients (19%) had triple-negative breast cancer. In E7389-G000-301, 150 patients (24.5%) had triple-negative breast cancer. KEYNOTE-119 did not specify capecitabine dosing, which was left to the local standard of care. This is the North American dosing in ASCENT.
Chemotherapy
- Eribulin (Halaven) 1.4 mg/m2 IV over 2 to 5 minutes once per day on days 1 & 8
21-day cycles
References
- EMBRACE: Cortes J, O'Shaughnessy J, Loesch D, Blum JL, Vahdat LT, Petrakova K, Chollet P, Manikas A, Diéras V, Delozier T, Vladimirov V, Cardoso F, Koh H, Bougnoux P, Dutcus CE, Seegobin S, Mir D, Meneses N, Wanders J, Twelves C; EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician's Choice Versus E7389) investigators. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet. 2011 Mar 12;377(9769):914-23. Epub 2011 Mar 2. link to original article contains protocol PubMed NCT00388726
- E7389-G000-301: Kaufman PA, Awada A, Twelves C, Yelle L, Perez EA, Velikova G, Olivo MS, He Y, Dutcus CE, Cortes J. Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2015 Feb 20;33(6):594-601. Epub 2015 Jan 20. link to original article link to PMC article contains verified protocol PubMed NCT00337103
- KEYNOTE-119: Winer EP, Lipatov O, Im SA, Goncalves A, Muñoz-Couselo E, Lee KS, Schmid P, Tamura K, Testa L, Witzel I, Ohtani S, Turner N, Zambelli S, Harbeck N, Andre F, Dent R, Zhou X, Karantza V, Mejia J, Cortes J; KEYNOTE-119 investigators. Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Apr;22(4):499-511. Epub 2021 Mar 4. link to original article does not contain protocol PubMed NCT02555657
- ASCENT: Bardia A, Hurvitz SA, Tolaney SM, Loirat D, Punie K, Oliveira M, Brufsky A, Sardesai SD, Kalinsky K, Zelnak AB, Weaver R, Traina T, Dalenc F, Aftimos P, Lynce F, Diab S, Cortés J, O'Shaughnessy J, Diéras V, Ferrario C, Schmid P, Carey LA, Gianni L, Piccart MJ, Loibl S, Goldenberg DM, Hong Q, Olivo MS, Itri LM, Rugo HS; ASCENT Clinical Trial Investigators. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med. 2021 Apr 22;384(16):1529-1541. link to original article contains verified protocol PubMed NCT02574455
Gemcitabine monotherapy
Regimen variant #1, 800 mg/m2 3 weeks out of 4
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bardia et al. 2021 (ASCENT) | 2017-2019 | Phase III (C) | Sacituzumab govitecan | Inferior OS |
Note: This is the lower bound of dosing specified by ASCENT.
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
Regimen variant #2, 1000 mg/m2 3 weeks out of 4
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Winer et al. 2021 (KEYNOTE-119) | 2015-2017 | Phase III (C) | Pembrolizumab | Did not meet primary endpoint of OS |
Note: KEYNOTE-119 did not specify gemcitabine dosing, which was left to the local standard of care. This is a gemcitabine dosing schema used in recent phase 3 RCTs.
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
Regimen variant #3, 1200 mg/m2 3 weeks out of 4
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bardia et al. 2021 (ASCENT) | 2017-2019 | Phase III (C) | Sacituzumab govitecan | Inferior OS |
Note: This is the upper bound of dosing specified by ASCENT.
Chemotherapy
- Gemcitabine (Gemzar) 1200 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
Regimen variant #4, 1250 mg/m2 2 weeks out of 3
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Winer et al. 2021 (KEYNOTE-119) | 2015-2017 | Phase III (C) | Pembrolizumab | Did not meet primary endpoint of OS |
Note: KEYNOTE-119 did not specify gemcitabine dosing, which was left to the local standard of care. This is a gemcitabine dosing schema used in recent phase 3 RCTs.
Chemotherapy
- Gemcitabine (Gemzar) 1250 mg/m2 IV over 30 minutes once per day on days 1 & 8
21-day cycles
References
- KEYNOTE-119: Winer EP, Lipatov O, Im SA, Goncalves A, Muñoz-Couselo E, Lee KS, Schmid P, Tamura K, Testa L, Witzel I, Ohtani S, Turner N, Zambelli S, Harbeck N, Andre F, Dent R, Zhou X, Karantza V, Mejia J, Cortes J; KEYNOTE-119 investigators. Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Apr;22(4):499-511. Epub 2021 Mar 4. link to original article does not contain protocol PubMed NCT02555657
- ASCENT: Bardia A, Hurvitz SA, Tolaney SM, Loirat D, Punie K, Oliveira M, Brufsky A, Sardesai SD, Kalinsky K, Zelnak AB, Weaver R, Traina T, Dalenc F, Aftimos P, Lynce F, Diab S, Cortés J, O'Shaughnessy J, Diéras V, Ferrario C, Schmid P, Carey LA, Gianni L, Piccart MJ, Loibl S, Goldenberg DM, Hong Q, Olivo MS, Itri LM, Rugo HS; ASCENT Clinical Trial Investigators. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med. 2021 Apr 22;384(16):1529-1541. link to original article contains verified protocol PubMed NCT02574455
Sacituzumab govitecan monotherapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bardia et al. 2017 (IMMU-132-01) | 2013-2016 | Phase I/II (RT) | ||
Bardia et al. 2021 (ASCENT) | 2017-2019 | Phase III (E-RT-switch-ooc) | 1. Capecitabine 2. Eribulin 3. Gemcitabine 4. Vinorelbine | Superior OS Median OS: 12 mo vs 7 mo (HR 0.49, 95% CI 0.38-0.59) |
Antibody-drug conjugate therapy
- Sacituzumab govitecan (Trodelvy) 10 mg/kg IV once per day on days 1 & 8
21-day cycles
References
- IMMU-132-01: Bardia A, Mayer IA, Diamond JR, Moroose RL, Isakoff SJ, Starodub AN, Shah NC, O'Shaughnessy J, Kalinsky K, Guarino M, Abramson V, Juric D, Tolaney SM, Berlin J, Messersmith WA, Ocean AJ, Wegener WA, Maliakal P, Sharkey RM, Govindan SV, Goldenberg DM, Vahdat LT. Efficacy and Safety of Anti-Trop-2 Antibody Drug Conjugate Sacituzumab Govitecan (IMMU-132) in Heavily Pretreated Patients With Metastatic Triple-Negative Breast Cancer. J Clin Oncol. 2017 Jul 1;35(19):2141-2148. Epub 2017 Mar 14. link to original article link to PMC article PubMed NCT01631552
- Update: Bardia A, Mayer IA, Vahdat LT, Tolaney SM, Isakoff SJ, Diamond JR, O'Shaughnessy J, Moroose RL, Santin AD, Abramson VG, Shah NC, Rugo HS, Goldenberg DM, Sweidan AM, Iannone R, Washkowitz S, Sharkey RM, Wegener WA, Kalinsky K. Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. N Engl J Med. 2019 Feb 21;380(8):741-751. link to original article PubMed
- ASCENT: Bardia A, Hurvitz SA, Tolaney SM, Loirat D, Punie K, Oliveira M, Brufsky A, Sardesai SD, Kalinsky K, Zelnak AB, Weaver R, Traina T, Dalenc F, Aftimos P, Lynce F, Diab S, Cortés J, O'Shaughnessy J, Diéras V, Ferrario C, Schmid P, Carey LA, Gianni L, Piccart MJ, Loibl S, Goldenberg DM, Hong Q, Olivo MS, Itri LM, Rugo HS; ASCENT Clinical Trial Investigators. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med. 2021 Apr 22;384(16):1529-1541. link to original article contains verified protocol PubMed NCT02574455
Vinorelbine monotherapy
Regimen variant #1, 25 mg/m2 weekly
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bardia et al. 2021 (ASCENT) | 2017-2019 | Phase III (C) | Sacituzumab govitecan | Inferior OS |
Chemotherapy
- Vinorelbine (Navelbine) 25 mg/m2 IV once per day on days 1, 8, 15
21-day cycles
Regimen variant #2, 30 mg/m2 weekly
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Winer et al. 2021 (KEYNOTE-119) | 2015-2017 | Phase III (C) | Pembrolizumab | Did not meet primary endpoint of OS |
Note: KEYNOTE-119 did not specify vinorelbine dosing, which was left to the local standard of care. This is a vinorelbine dosing schema used in recent phase 3 RCTs.
Chemotherapy
- Vinorelbine (Navelbine) 30 mg/m2 IV once per day on days 1, 8, 15
21-day cycles
Regimen variant #3, 30 mg/m2 q3wk
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Winer et al. 2021 (KEYNOTE-119) | 2015-2017 | Phase III (C) | Pembrolizumab | Did not meet primary endpoint of OS |
Note: KEYNOTE-119 did not specify vinorelbine dosing, which was left to the local standard of care. This is a vinorelbine dosing schema used in recent phase 3 RCTs.
Chemotherapy
- Vinorelbine (Navelbine) 30 mg/m2 IV once on day 1
21-day cycles
Regimen variant #4, 30 mg/m2 2 out of 3 weeks
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Winer et al. 2021 (KEYNOTE-119) | 2015-2017 | Phase III (C) | Pembrolizumab | Did not meet primary endpoint of OS |
Note: KEYNOTE-119 did not specify vinorelbine dosing, which was left to the local standard of care. This is a vinorelbine dosing schema used in recent phase 3 RCTs.
Chemotherapy
- Vinorelbine (Navelbine) 30 mg/m2 IV once per day on days 1 & 8
21-day cycles
References
- KEYNOTE-119: Winer EP, Lipatov O, Im SA, Goncalves A, Muñoz-Couselo E, Lee KS, Schmid P, Tamura K, Testa L, Witzel I, Ohtani S, Turner N, Zambelli S, Harbeck N, Andre F, Dent R, Zhou X, Karantza V, Mejia J, Cortes J; KEYNOTE-119 investigators. Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Apr;22(4):499-511. Epub 2021 Mar 4. link to original article does not contain protocol PubMed NCT02555657
- ASCENT: Bardia A, Hurvitz SA, Tolaney SM, Loirat D, Punie K, Oliveira M, Brufsky A, Sardesai SD, Kalinsky K, Zelnak AB, Weaver R, Traina T, Dalenc F, Aftimos P, Lynce F, Diab S, Cortés J, O'Shaughnessy J, Diéras V, Ferrario C, Schmid P, Carey LA, Gianni L, Piccart MJ, Loibl S, Goldenberg DM, Hong Q, Olivo MS, Itri LM, Rugo HS; ASCENT Clinical Trial Investigators. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med. 2021 Apr 22;384(16):1529-1541. link to original article contains verified protocol PubMed NCT02574455
Investigational agents
Drugs with some degree of promising activity in clinical trials.
Triple Negative Breast Cancer Plant Based Diet
Source: https://hemonc.org/wiki/Breast_cancer,_triple_negative