Breast cancer, BRCA-mutated

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Note: this page has regimens which are specific to breast cancer that is BRCA-mutated. Please see the main breast cancer page for other chemotherapy regimens.
*Regimens for Triple negative breast cancer (TNBC) are here.
Last updated on 2024-07-23:10 regimens on this page
13 variants on this page
=Guidelines=
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
==ASCO==
*2024: Bedrosian et al. Germline Testing in Patients With Breast Cancer: ASCO–Society of Surgical Oncology Guideline EuroPMC
*2021: Tung et al. Adjuvant PARP Inhibitors in Patients With High-Risk Early-Stage HER2-Negative Breast Cancer and Germline BRCA Mutations: ASCO Hereditary Breast Cancer Guideline Rapid Recommendation Update EuroPMC
*2020: Tung et al. Management of Hereditary Breast Cancer: American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Guideline EuroPMC
==ESMO==
*2011: Balmaña et al. BRCA in breast cancer: ESMO Clinical Practice Guidelines EuroPMC
==NCCN==
*NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Breast Cancer.
=Adjuvant therapy=
==Olaparib monotherapy==
===Regimen===
FDA-recommended dose
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Tutt et al. 2021 (OlympiA)	2014-2019 	Phase 3 (E-RT-esc)	Placebo 	Longer iDFS (primary endpoint)iDFS36: 85.9% vs 77.1%(HR 0.58, 99.5% CI 0.41-0.82)Longer OS1 (secondary endpoint)OS48: 89.8% vs 86.4%(HR 0.68, 98.5% CI 0.47-0.97)
1Reported efficacy is based on the 2022 update.
====Preceding treatment====
*Primary local treatment +/- (neo-)adjuvant therapy
====Targeted therapy====
*Olaparib (Lynparza) 300 mg PO twice per day
28-day cycle for 13 cycles (1 year)
===References===
# OlympiA: Tutt ANJ, Garber JE, Kaufman B, Viale G, Fumagalli D, Rastogi P, Gelber RD, de Azambuja E, Fielding A, Balmaña J, Domchek SM, Gelmon KA, Hollingsworth SJ, Korde LA, Linderholm B, Bandos H, Senkus E, Suga JM, Shao Z, Pippas AW, Nowecki Z, Huzarski T, Ganz PA, Lucas PC, Baker N, Loibl S, McConnell R, Piccart M, Schmutzler R, Steger GG, Costantino JP, Arahmani A, Wolmark N, McFadden E, Karantza V, Lakhani SR, Yothers G, Campbell C, Geyer CE Jr; OlympiA Clinical Trial Steering Committee and Investigators. Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer. N Engl J Med. 2021 Jun 24;384(25):2394-2405. Epub 2021 Jun 3. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT02032823
##Update: Geyer CE Jr, Garber JE, Gelber RD, Yothers G, Taboada M, Ross L, Rastogi P, Cui K, Arahmani A, Aktan G, Armstrong AC, Arnedos M, Balmaña J, Bergh J, Bliss J, Delaloge S, Domchek SM, Eisen A, Elsafy F, Fein LE, Fielding A, Ford JM, Friedman S, Gelmon KA, Gianni L, Gnant M, Hollingsworth SJ, Im SA, Jager A, Jóhannsson ÓÞ, Lakhani SR, Janni W, Linderholm B, Liu TW, Loman N, Korde L, Loibl S, Lucas PC, Marmé F, Martinez de Dueñas E, McConnell R, Phillips KA, Piccart M, Rossi G, Schmutzler R, Senkus E, Shao Z, Sharma P, Singer CF, Španić T, Stickeler E, Toi M, Traina TA, Viale G, Zoppoli G, Park YH, Yerushalmi R, Yang H, Pang D, Jung KH, Mailliez A, Fan Z, Tennevet I, Zhang J, Nagy T, Sonke GS, Sun Q, Parton M, Colleoni MA, Schmidt M, Brufsky AM, Razaq W, Kaufman B, Cameron D, Campbell C, Tutt ANJ; OlympiA Clinical Trial Steering Committee and Investigators. Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer. Ann Oncol. 2022 Dec 1;33(12):1250-1268. Epub 2022 Oct 10. link to original article link to PMC article EuroPMC
##PRO analysis: Ganz PA, Bandos H, Španić T, Friedman S, Müller V, Kuemmel S, Delaloge S, Brain E, Toi M, Yamauchi H, de Dueñas EM, Armstrong A, Im SA, Song CG, Zheng H, Sarosiek T, Sharma P, Geng C, Fu P, Rhiem K, Frauchiger-Heuer H, Wimberger P, t'Kint de Roodenbeke D, Liao N, Goodwin A, Chakiba-Brugère C, Friedlander M, Lee KS, Giacchetti S, Takano T, Henao-Carrasco F, Virani S, Valdes-Albini F, Domchek SM, Bane C, McCarron EC, Mita M, Rossi G, Rastogi P, Fielding A, Gelber RD, Scheepers ED, Cameron D, Garber J, Geyer CE, Tutt ANJ. Patient-Reported Outcomes in OlympiA: A Phase III, Randomized, Placebo-Controlled Trial of Adjuvant Olaparib in gBRCA1/2 Mutations and High-Risk Human Epidermal Growth Factor Receptor 2-Negative Early Breast Cancer. J Clin Oncol. 2024 Apr 10;42(11):1288-1300. Epub 2024 Feb 1. link to original article link to PMC article EuroPMC
=Advanced or metastatic disease, subsequent lines of therapy=
==Capecitabine monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Litton et al. 2018 (EMBRACA) 	2013-10 to 2017-04 	Phase 3 (C)	Talazoparib	Shorter PFSMedian PFS: 5.6 vs 8.6 mo(HR 1.85, 95% CI 1.41-2.44)Did not meet secondary endpoint of OS1Median OS: 19.5 vs 19.3 mo(HR 1.18, 95% CI 0.93-1.49)
Robson et al. 2017 (OlympiAD)	2014-04-07 to 2015-11-27	Phase 3 (C)	Olaparib 	Shorter PFSMedian PFS: 4.2 vs 7 mo(HR 1.72, 95% CI 1.25-2.33)Did not meet secondary endpoint of OS2Median OS: 17.1 vs 19.3 mo(HR 1.11, 95% CI 0.81-1.52)
1Reported OS efficacy for EMBRACA is based on the 2020 update.
2Reported OS efficacy for OlympiAD is based on the 2019 update.
====Biomarker eligibility criteria====
*EMBRACA: Germline BRCA1 or BRCA2 mutation
*OlympiAD: Confirmed deleterious or suspected deleterious germline BRCA mutation
====Chemotherapy====
*Capecitabine (Xeloda) 1250 mg/m2 PO twice per day on days 1 to 14
21-day cycles
===References===
# OlympiAD: Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. Epub 2017 Jun 4. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02000622
## Update: Robson ME, Tung N, Conte P, Im SA, Senkus E, Xu B, Masuda N, Delaloge S, Li W, Armstrong A, Wu W, Goessl C, Runswick S, Domchek SM. OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician's choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer. Ann Oncol. 2019 Apr 1;30(4):558-566. link to original article link to PMC article EuroPMC
# EMBRACA: Litton JK, Rugo HS, Ettl J, Hurvitz SA, Gonçalves A, Lee KH, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Quek RGW, Markova D, Tudor IC, Hannah AL, Eiermann W, Blum JL. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 2018 Aug 23;379(8):753-763. Epub 2018 Aug 15. link to original article dosing details in supplement have been reviewed by our editors link to PMC article EuroPMC NCT01945775
##PRO analysis: Ettl J, Quek RGW, Lee KH, Rugo HS, Hurvitz S, Gonçalves A, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Markova D, Bhattacharyya H, Hannah AL, Eiermann W, Blum JL, Litton JK. Quality of life with talazoparib versus physician's choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial. Ann Oncol. 2018 Sep 1;29(9):1939-1947. link to original article EuroPMC
## Update: Litton JK, Hurvitz SA, Mina LA, Rugo HS, Lee KH, Gonçalves A, Diab S, Woodward N, Goodwin A, Yerushalmi R, Roché H, Im YH, Eiermann W, Quek RGW, Usari T, Lanzalone S, Czibere A, Blum JL, Martin M, Ettl J. Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial. Ann Oncol. 2020 Nov;31(11):1526-1535. Epub 2020 Aug 20. link to original article link to PMC article EuroPMC
#FZPL-III-303: NCT04296370
==Carboplatin monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Tutt et al. 2018 (TNT)	2008-2014 	Phase 3 (E-switch-ic)	Docetaxel 	Higher ORR1 (primary endpoint)
1Reported efficacy is based on subgroup analysis.
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 6 IV once on day 1
21-day cycle for 6 to 8 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00532727
==Carboplatin & Paclitaxel (CP)==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Diéras et al. 2020 (BROCADE3)	2014-2018 	Phase 3 (C)	CP & Veliparib	Shorter PFS (primary endpoint)Median PFS: 12.6 vs 14.5 mo(HR 1.41, 95% CI 1.14-1.75)Did not meet secondary endpoint of OS1Median OS: 28.2 vs 32.4 mo(HR 1.09, 95% CI 0.88-1.35)
1Reported efficacy is based on the 2024 update.
====Biomarker eligibility criteria====
*Confirmed deleterious germline BRCA1 or BRCA2 mutation
====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 cycles
===References===
#BROCADE3: Diéras V, Han HS, Kaufman B, Wildiers H, Friedlander M, Ayoub JP, Puhalla SL, Bondarenko I, Campone M, Jakobsen EH, Jalving M, Oprean C, Palácová M, Park YH, Shparyk Y, Yañez E, Khandelwal N, Kundu MG, Dudley M, Ratajczak CK, Maag D, Arun BK. Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 Oct;21(10):1269-1282. Epub 2020 Aug 27. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02163694
##Update: Diéras V, Han HS, Wildiers H, Friedlander M, Ayoub JP, Puhalla SL, Loirat D, Ratajczak C, Adamu H, Girardi V, Arun BK. Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3): Final overall survival results from a randomized phase 3 trial. Eur J Cancer. 2024 Mar;200:113580. Epub 2024 Jan 28. link to original article EuroPMC
==Docetaxel monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Tutt et al. 2018 (TNT)	2008-2014 	Phase 3 (C)	Carboplatin	Lower ORR1
1Reported efficacy is based on subgroup analysis.
====Chemotherapy====
*Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
21-day cycle for 6 to 8 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00532727
==Eribulin monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Litton et al. 2018 (EMBRACA) 	2013-10 to 2017-04 	Phase 3 (C)	Talazoparib	Shorter PFSMedian PFS: 5.6 vs 8.6 mo(HR 1.85, 95% CI 1.41-2.44)Did not meet secondary endpoint of OS1Median OS: 19.5 vs 19.3 mo(HR 1.18, 95% CI 0.93-1.49)
Robson et al. 2017 (OlympiAD)	2014-04-07 to 2015-11-27	Phase 3 (C)	Olaparib 	Shorter PFSMedian PFS: 4.2 vs 7 mo(HR 1.72, 95% CI 1.25-2.33)Did not meet secondary endpoint of OS2Median OS: 17.1 vs 19.3 mo(HR 1.11, 95% CI 0.81-1.52)
1Reported OS efficacy for EMBRACA is based on the 2020 update.
2Reported OS efficacy for OlympiAD is based on the 2019 update.
====Biomarker eligibility criteria====
*EMBRACA: Germline BRCA1 or BRCA2 mutation
*OlympiAD: Confirmed deleterious or suspected deleterious germline BRCA mutation
====Chemotherapy====
*Eribulin (Halaven) 1.4 mg/m2 IV over 2 to 5 minutes once per day on days 1 & 8
21-day cycles
===References===
# OlympiAD: Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. Epub 2017 Jun 4. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02000622
## Update: Robson ME, Tung N, Conte P, Im SA, Senkus E, Xu B, Masuda N, Delaloge S, Li W, Armstrong A, Wu W, Goessl C, Runswick S, Domchek SM. OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician's choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer. Ann Oncol. 2019 Apr 1;30(4):558-566. link to original article link to PMC article EuroPMC
# EMBRACA: Litton JK, Rugo HS, Ettl J, Hurvitz SA, Gonçalves A, Lee KH, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Quek RGW, Markova D, Tudor IC, Hannah AL, Eiermann W, Blum JL. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 2018 Aug 23;379(8):753-763. Epub 2018 Aug 15. link to original article dosing details in supplement have been reviewed by our editors link to PMC article EuroPMC NCT01945775
##PRO analysis: Ettl J, Quek RGW, Lee KH, Rugo HS, Hurvitz S, Gonçalves A, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Markova D, Bhattacharyya H, Hannah AL, Eiermann W, Blum JL, Litton JK. Quality of life with talazoparib versus physician's choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial. Ann Oncol. 2018 Sep 1;29(9):1939-1947. link to original article EuroPMC
## Update: Litton JK, Hurvitz SA, Mina LA, Rugo HS, Lee KH, Gonçalves A, Diab S, Woodward N, Goodwin A, Yerushalmi R, Roché H, Im YH, Eiermann W, Quek RGW, Usari T, Lanzalone S, Czibere A, Blum JL, Martin M, Ettl J. Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial. Ann Oncol. 2020 Nov;31(11):1526-1535. Epub 2020 Aug 20. link to original article link to PMC article EuroPMC
==Gemcitabine monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Litton et al. 2018 (EMBRACA)	2013-10 to 2017-04 	Phase 3 (C)	Talazoparib	Shorter PFSMedian PFS: 5.6 vs 8.6 mo(HR 1.85, 95% CI 1.41-2.44)Did not meet secondary endpoint of OS1Median OS: 19.5 vs 19.3 mo(HR 1.18, 95% CI 0.93-1.49)
1Reported OS efficacy is based on the 2020 update.
====Biomarker eligibility criteria====
*Germline BRCA1 or BRCA2 mutation
====Chemotherapy====
*Gemcitabine (Gemzar) 1250 mg/m2 IV over 30 minutes once per day on days 1 & 8
21-day cycles
===References===
# EMBRACA: Litton JK, Rugo HS, Ettl J, Hurvitz SA, Gonçalves A, Lee KH, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Quek RGW, Markova D, Tudor IC, Hannah AL, Eiermann W, Blum JL. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 2018 Aug 23;379(8):753-763. Epub 2018 Aug 15. link to original article dosing details in supplement have been reviewed by our editors link to PMC article EuroPMC NCT01945775
##PRO analysis: Ettl J, Quek RGW, Lee KH, Rugo HS, Hurvitz S, Gonçalves A, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Markova D, Bhattacharyya H, Hannah AL, Eiermann W, Blum JL, Litton JK. Quality of life with talazoparib versus physician's choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial. Ann Oncol. 2018 Sep 1;29(9):1939-1947. link to original article EuroPMC
## Update: Litton JK, Hurvitz SA, Mina LA, Rugo HS, Lee KH, Gonçalves A, Diab S, Woodward N, Goodwin A, Yerushalmi R, Roché H, Im YH, Eiermann W, Quek RGW, Usari T, Lanzalone S, Czibere A, Blum JL, Martin M, Ettl J. Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial. Ann Oncol. 2020 Nov;31(11):1526-1535. Epub 2020 Aug 20. link to original article link to PMC article EuroPMC
#FZPL-III-303: NCT04296370
==Olaparib monotherapy==
===Regimen variant #1, 100 mg twice per day===
Study 	Dates of enrollment	Evidence
Tutt et al. 2010 (KU36-44)	2007-2008 	Phase 2
====Targeted therapy====
*Olaparib (Lynparza) 100 mg PO twice per day
Continued indefinitely
===Regimen variant #2, 300 mg twice per day===
FDA-recommended dose
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Robson et al. 2017 (OlympiAD)	2014-04-07 to 2015-11-27	Phase 3 (E-RT-switch-ooc)	Investigator's choice of:1a. Capecitabine1b. Eribulin1c. Vinorelbine	Longer PFS (primary endpoint)Median PFS: 7.0 vs 4.2 mo (HR 0.58, 95% CI 0.43-0.80)Did not meet secondary endpoint of OS1Median OS: 19.3 vs 17.1 mo(HR 0.90, 95% CI 0.66-1.23)
1Reported OS efficacy is based on the 2019 update.
====Biomarker eligibility criteria====
*Confirmed deleterious or suspected deleterious germline BRCA mutation
====Targeted therapy====
*Olaparib (Lynparza) 300 mg PO twice per day
Continued indefinitely
===Regimen variant #3, 400 mg twice per day===
Study 	Dates of enrollment 	Evidence
Tutt et al. 2010 (KU36-44) 	2007-2008 	Phase 2
Kaufman et al. 2014 (Study 42)	2010-02-21 to 2012-07-31	Phase 2
====Biomarker eligibility criteria====
*Study 42: Germline BRCA1/2 mutations
====Prior treatment criteria====
*Study 42: Progression after at least three lines of treatment for metastatic disease.
====Targeted therapy====
*Olaparib (Lynparza) 400 mg PO twice per day
Continued indefinitely
===References===
# KU36-44: Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, Friedlander M, Arun B, Loman N, Schmutzler RK, Wardley A, Mitchell G, Earl H, Wickens M, Carmichael J. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet. 2010 Jul 24;376(9737):235-44. Epub 2010 Jul 6. link to original article EuroPMC NCT00494234
# Study 42: Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Steiner M, Loman N, Bowen K, Fielding A, Domchek SM. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015 Jan 20;33(3):244-50. Epub 2014 Nov 3. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT01078662
# OlympiAD: Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. Epub 2017 Jun 4. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02000622
## Update: Robson ME, Tung N, Conte P, Im SA, Senkus E, Xu B, Masuda N, Delaloge S, Li W, Armstrong A, Wu W, Goessl C, Runswick S, Domchek SM. OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician's choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer. Ann Oncol. 2019 Apr 1;30(4):558-566. link to original article link to PMC article EuroPMC
==Talazoparib monotherapy==
===Regimen===
FDA-recommended dose
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Turner et al. 2018 (ABRAZO) 	2014-05 to 2016-02 	Phase 2 	 	
Litton et al. 2018 (EMBRACA)	2013-10 to 2017-04 	Phase 3 (E-RT-switch-ooc)	Physician's choice of:1a. Capecitabine1b. Eribulin1c. Gemcitabine1d. Vinorelbine	Longer PFS (primary endpoint)Median PFS: 8.6 vs 5.6 mo(HR 0.54, 95% CI 0.41-0.71)Did not meet secondary endpoint of OS1Median OS: 19.3 vs 19.5 mo(HR 0.85, 95% CI 0.67-1.07)
1Reported OS efficacy for EMBRACA is based on the 2020 update.
====Biomarker eligibility criteria====
*Germline BRCA1 or BRCA2 mutation
====Targeted therapy====
*Talazoparib (Talzenna) 1 mg PO once per day
Continued indefinitely
===References===
# ABRAZO: Turner NC, Telli ML, Rugo HS, Mailliez A, Ettl J, Grischke EM, Mina LA, Balmaña J, Fasching PA, Hurvitz SA, Wardley AM, Chappey C, Hannah AL, Robson ME; ABRAZO Study Group. A Phase II Study of Talazoparib after Platinum or Cytotoxic Nonplatinum Regimens in Patients with Advanced Breast Cancer and Germline BRCA1/2 Mutations (ABRAZO). Clin Cancer Res. 2019 May 1;25(9):2717-2724. Epub 2018 Dec 18. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02034916
# EMBRACA: Litton JK, Rugo HS, Ettl J, Hurvitz SA, Gonçalves A, Lee KH, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Quek RGW, Markova D, Tudor IC, Hannah AL, Eiermann W, Blum JL. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 2018 Aug 23;379(8):753-763. Epub 2018 Aug 15. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT01945775
##PRO analysis: Ettl J, Quek RGW, Lee KH, Rugo HS, Hurvitz S, Gonçalves A, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Markova D, Bhattacharyya H, Hannah AL, Eiermann W, Blum JL, Litton JK. Quality of life with talazoparib versus physician's choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial. Ann Oncol. 2018 Sep 1;29(9):1939-1947. link to original article EuroPMC
## Update: Litton JK, Hurvitz SA, Mina LA, Rugo HS, Lee KH, Gonçalves A, Diab S, Woodward N, Goodwin A, Yerushalmi R, Roché H, Im YH, Eiermann W, Quek RGW, Usari T, Lanzalone S, Czibere A, Blum JL, Martin M, Ettl J. Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial. Ann Oncol. 2020 Nov;31(11):1526-1535. Epub 2020 Aug 20. link to original article link to PMC article EuroPMC
==Vinorelbine monotherapy==
===Regimen variant #1, 2 out of 3 weeks===
Study 	Dates of enrollment 	Evidence 	Comparator	Comparative Efficacy
Robson et al. 2017 (OlympiAD)	2014-04-07 to 2015-11-27	Phase 3 (C)	Olaparib 	Shorter PFSMedian PFS: 4.2 vs 7 mo(HR 1.72, 95% CI 1.25-2.33)Did not meet secondary endpoint of OS1Median OS: 17.1 vs 19.3 mo(HR 1.11, 95% CI 0.81-1.52)
1Reported OS efficacy is based on the 2019 update.
====Biomarker eligibility criteria====
*Confirmed deleterious or suspected deleterious germline BRCA mutation
====Chemotherapy====
*Vinorelbine (Navelbine) 30 mg/m2 IV once per day on days 1 & 8
21-day cycles
===Regimen variant #2, weekly===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Litton et al. 2018 (EMBRACA)	2013-10 to 2017-04 	Phase 3 (C)	Talazoparib	Shorter PFSMedian PFS: 5.6 vs 8.6 mo(HR 1.85, 95% CI 1.41-2.44)Did not meet secondary endpoint of OS1Median OS: 19.5 vs 19.3 mo(HR 1.18, 95% CI 0.93-1.49)
1Reported OS efficacy is based on the 2020 update.
====Biomarker eligibility criteria====
*Germline BRCA1 or BRCA2 mutation
====Chemotherapy====
*Vinorelbine (Navelbine) 30 mg/m2 IV over 6 to 10 minutes once per day on days 1, 8, 15
21-day cycles
===References===
# OlympiAD: Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. Epub 2017 Jun 4. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02000622
## Update: Robson ME, Tung N, Conte P, Im SA, Senkus E, Xu B, Masuda N, Delaloge S, Li W, Armstrong A, Wu W, Goessl C, Runswick S, Domchek SM. OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician's choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer. Ann Oncol. 2019 Apr 1;30(4):558-566. link to original article link to PMC article EuroPMC
# EMBRACA: Litton JK, Rugo HS, Ettl J, Hurvitz SA, Gonçalves A, Lee KH, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Quek RGW, Markova D, Tudor IC, Hannah AL, Eiermann W, Blum JL. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 2018 Aug 23;379(8):753-763. Epub 2018 Aug 15. link to original article dosing details in supplement have been reviewed by our editors link to PMC article EuroPMC NCT01945775
##PRO analysis: Ettl J, Quek RGW, Lee KH, Rugo HS, Hurvitz S, Gonçalves A, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roché H, Im YH, Markova D, Bhattacharyya H, Hannah AL, Eiermann W, Blum JL, Litton JK. Quality of life with talazoparib versus physician's choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial. Ann Oncol. 2018 Sep 1;29(9):1939-1947. link to original article EuroPMC
## Update: Litton JK, Hurvitz SA, Mina LA, Rugo HS, Lee KH, Gonçalves A, Diab S, Woodward N, Goodwin A, Yerushalmi R, Roché H, Im YH, Eiermann W, Quek RGW, Usari T, Lanzalone S, Czibere A, Blum JL, Martin M, Ettl J. Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial. Ann Oncol. 2020 Nov;31(11):1526-1535. Epub 2020 Aug 20. link to original article link to PMC article EuroPMC
=Additional resources=
*Breast cancer BRCA1 & BRCA2 genetic testing
*OncoMX -- BRCA1
*OncoMX -- BRCA2
Category:Breast cancer regimens
Category:Biomarker-specific pages
Category:Malignant breast neoplasm