Difference between revisions of "Breast cancer, BRCA-mutated"
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===References=== | ===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. [https://www.nature.com/articles/s41591-018-0009-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372067/ link to PMC article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/29713086 PubMed] | + | # '''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. [https://www.nature.com/articles/s41591-018-0009-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372067/ link to PMC article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/29713086 PubMed] NCT00532727 |
==Eribulin monotherapy {{#subobject:ef2415|Regimen=1}}== | ==Eribulin monotherapy {{#subobject:ef2415|Regimen=1}}== |
Revision as of 12:33, 6 August 2022
10 regimens on this page
13 variants on this page
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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.
Guidelines
ASCO
ESMO
- 2011: Balmaña et al. BRCA in breast cancer: ESMO Clinical Practice Guidelines
Adjuvant therapy
Olaparib monotherapy
Regimen
FDA-recommended dose |
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tutt et al. 2021 (OlympiA) | 2014-2019 | Phase 3 (E-RT-esc) | Placebo | Superior invasive DFS IDFS36: 86% vs 77% (HR 0.58, 99.5% CI 0.41-0.82) |
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 contains verified protocol PubMed NCT02032823
Advanced or metastatic disease, subsequent lines of therapy
Capecitabine monotherapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Litton et al. 2018 (EMBRACA) | 2013-2017 | Phase 3 (C) | Talazoparib | Inferior PFS |
Robson et al. 2017 (OlympiAD) | 2014-2015 | Phase 3 (C) | Olaparib | Inferior PFS |
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 contains verified protocol PubMed 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 PubMed
- 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 contains verified protocol in supplement PubMed NCT01945775
- 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 PubMed
Carboplatin monotherapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tutt et al. 2018 (TNT) | 2008-2014 | Phase 3 (E-switch-ic) | Docetaxel | Superior ORR1 |
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 contains verified protocol PubMed NCT00532727
Carboplatin & Paclitaxel (CP)
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Diéras et al. 2020 (BROCADE3) | 2014-2018 | Phase 3 (C) | CP & Veliparib | Inferior PFS |
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 contains verified protocol PubMed NCT02163694
Docetaxel monotherapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tutt et al. 2018 (TNT) | 2008-2014 | Phase 3 (C) | Carboplatin | Inferior 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 contains verified protocol PubMed NCT00532727
Eribulin monotherapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Litton et al. 2018 (EMBRACA) | 2013-2017 | Phase 3 (C) | Talazoparib | Inferior PFS |
Robson et al. 2017 (OlympiAD) | 2014-2015 | Phase 3 (C) | Olaparib | Inferior PFS |
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 contains verified protocol PubMed 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 PubMed
- 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 contains verified protocol in supplement PubMed NCT01945775
- 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 PubMed
Gemcitabine monotherapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Litton et al. 2018 (EMBRACA) | 2013-2017 | Phase 3 (C) | Talazoparib | Inferior PFS |
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 contains verified protocol in supplement PubMed NCT01945775
- 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 PubMed
Olaparib monotherapy
Regimen variant #1, 100 mg twice per day
Study | Years 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 | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Robson et al. 2017 (OlympiAD) | 2014-2015 | Phase 3 (E-RT-switch-ooc) | 1. Capecitabine 2. Eribulin 3. Vinorelbine |
Superior PFS Median PFS: 7.0 mo vs 4.2 mo (HR 0.58, 95% CI 0.43-0.80) |
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 | Years of enrollment | Evidence |
---|---|---|
Tutt et al. 2010 (KU36-44) | 2007-2008 | Phase 2 |
Kaufman et al. 2014 (Study 42) | 2010-NR | Phase 2 |
Patients in Study 42 had germline BRCA1/2 mutations and had progressed 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 PubMed 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 contains verified protocol link to PMC article PubMed 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 contains verified protocol PubMed 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 PubMed
Talazoparib monotherapy
Regimen
FDA-recommended dose |
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Litton et al. 2018 (EMBRACA) | 2013-2017 | Phase 3 (E-RT-switch-ooc) | Physician's choice of: 1. Capecitabine 2. Eribulin 3. Gemcitabine 4. Vinorelbine |
Superior PFS Median PFS: 8.6 vs 5.6 mo (HR 0.54, 95% CI 0.41-0.71) |
Biomarker eligibility criteria
- Germline BRCA1 or BRCA2 mutation
Targeted therapy
- Talazoparib (Talzenna) 1 mg PO once per day
Continued indefinitely
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 contains protocol PubMed NCT01945775
- 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 PubMed
Vinorelbine monotherapy
Regimen variant #1, 2 out of 3 weeks
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Robson et al. 2017 (OlympiAD) | 2014-2015 | Phase 3 (C) | Olaparib | Inferior PFS |
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 | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Litton et al. 2018 (EMBRACA) | 2013-2017 | Phase 3 (C) | Talazoparib | Inferior PFS |
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 contains verified protocol PubMed 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 PubMed
- 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 contains verified protocol in supplement PubMed NCT01945775
- 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 PubMed