Prostate cancer, BRCA-mutated

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Laura S. Graham, MD
University of Colorado Anschutz Medical Campus
Aurora, CO, USA
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Ali Raza Khaki, MD
Stanford University
Palo Alto, CA, USA
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Last updated on 2024-09-06:
8 regimens on this page
9 variants on this page

Note: this page has regimens which are specific to prostate cancer that is BRCA-mutated. Please see the main prostate cancer page for other regimens.


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.

NCCN


Metastatic castration-resistant

Abiraterone monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Fizazi et al. 2023 (TRITON3) 2017-02-08 to 2022-02-02 Phase 3 (C) Rucaparib Inferior PFSi (primary endpoint)
de Bono et al. 2020 (PROfound) 2017-04 to 2018-11 Phase 3 (C) Olaparib Seems to have inferior OS
Chi et al. 2023 (MAGNITUDE) 2019-05 to 2021-03 Phase 3 (C) Abiraterone & Niraparib Inferior rPFS

Endocrine therapy

Supportive therapy

28-day cycles

References

  1. PROfound: de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Mehra N, Goessl C, Kang J, Burgents J, Wu W, Kohlmann A, Adelman CA, Hussain M. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 May 28;382(22):2091-2102. Epub 2020 Apr 28. link to original article dosing details in manuscript have been reviewed by our editors link to supplementary appendix PubMed NCT02987543
    1. Update: Hussain M, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Roubaud G, Özgüroğlu M, Kang J, Burgents J, Gresty C, Corcoran C, Adelman CA, de Bono J; PROfound Trial Investigators. Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 Dec 10;383(24):2345-2357. Epub 2020 Sep 20. link to original article PubMed
    2. HRQoL analysis: Thiery-Vuillemin A, de Bono J, Hussain M, Roubaud G, Procopio G, Shore N, Fizazi K, Dos Anjos G, Gravis G, Joung JY, Matsubara N, Castellano D, Degboe A, Gresty C, Kang J, Allen A, Poehlein C, Saad F. Pain and health-related quality of life with olaparib versus physician's choice of next-generation hormonal drug in patients with metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations (PROfound): an open-label, randomised, phase 3 trial. Lancet Oncol. 2022 Mar;23(3):393-405. Epub 2022 Feb 11. Erratum in: Lancet Oncol. 2022 Apr;23(4):e161. link to original article PubMed
  2. TRITON3: Fizazi K, Piulats JM, Reaume MN, Ostler P, McDermott R, Gingerich JR, Pintus E, Sridhar SS, Bambury RM, Emmenegger U, Lindberg H, Morris D, Nole F, Staffurth J, Redfern C, Saez MI, Abida W, Daugaard G, Heidenreich A, Krieger L, Sautois B, Loehr A, Despain D, Heyes CA, Watkins SP, Chowdhury S, Ryan CJ, Bryce AH. Rucaparib or Physician's Choice in Metastatic Prostate Cancer. N Engl J Med. 2023 Feb 23;388(8):719-732. Epub 2023 Feb 16. link to original article link to PMC article dosing details in supplement have been reviewed by our editors PubMed NCT02975934
  3. MAGNITUDE: Chi KN, Rathkopf D, Smith MR, Efstathiou E, Attard G, Olmos D, Lee JY, Small EJ, Pereira de Santana Gomes AJ, Roubaud G, Saad M, Zurawski B, Sakalo V, Mason GE, Francis P, Wang G, Wu D, Diorio B, Lopez-Gitlitz A, Sandhu S; MAGNITUDE Principal Investigators. Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer. J Clin Oncol. 2023 Jun 20;41(18):3339-3351. Epub 2023 Mar 23. link to original article link to PMC article PubMed NCT03748641
    1. Update: Chi KN, Sandhu S, Smith MR, Attard G, Saad M, Olmos D, Castro E, Roubaud G, Pereira de Santana Gomes AJ, Small EJ, Rathkopf DE, Gurney H, Jung W, Mason GE, Dibaj S, Wu D, Diorio B, Urtishak K, Del Corral A, Francis P, Kim W, Efstathiou E. Niraparib plus abiraterone acetate with prednisone in patients with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations: second interim analysis of the randomized phase III MAGNITUDE trial. Ann Oncol. 2023 Sep;34(9):772-782. Epub 2023 Jul 1. link to original article link to PMC article PubMed


Abiraterone & Niraparib

Regimen

Study Dates of enrollment Evidence
Saad et al. 2021 (BEDIVERE) 2016-10-24 to 2019-07-16 Phase 1b

Note: This was the RP2D which was used in the MAGNITUDE trial (see below; MAGNITUDE used a combination pill and is considered a different regimen).

Endocrine therapy

Targeted therapy

Supportive therapy

Continued indefinitely

References

  1. BEDIVERE: Saad F, Chi KN, Shore ND, Graff JN, Posadas EM, Lattouf JB, Espina BM, Zhu E, Yu A, Hazra A, De Meulder M, Mamidi RNVS, Bradic B, Francis P, Hayreh V, Rezazadeh Kalebasty A. Niraparib with androgen receptor-axis-targeted therapy in patients with metastatic castration-resistant prostate cancer: safety and pharmacokinetic results from a phase 1b study (BEDIVERE). Cancer Chemother Pharmacol. 2021 Jul;88(1):25-37. Epub 2021 Mar 22. link to original article link to PMC article PubMed NCT02924766


Abiraterone & Niraparib (combined pill)

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Chi et al. 2023 (MAGNITUDE) 2019-05 to 2021-03 Phase 3 (E-RT-esc) Abiraterone Superior rPFS (primary endpoint)
Median rPFS: 16.6 vs 10.9 mo
(HR 0.53, 95% CI 0.36-0.79)

Anticancer therapy

Supportive therapy

Continued indefinitely

References

  1. MAGNITUDE: Chi KN, Rathkopf D, Smith MR, Efstathiou E, Attard G, Olmos D, Lee JY, Small EJ, Pereira de Santana Gomes AJ, Roubaud G, Saad M, Zurawski B, Sakalo V, Mason GE, Francis P, Wang G, Wu D, Diorio B, Lopez-Gitlitz A, Sandhu S; MAGNITUDE Principal Investigators. Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer. J Clin Oncol. 2023 Jun 20;41(18):3339-3351. Epub 2023 Mar 23. link to original article link to PMC article PubMed NCT03748641
    1. Update: Chi KN, Sandhu S, Smith MR, Attard G, Saad M, Olmos D, Castro E, Roubaud G, Pereira de Santana Gomes AJ, Small EJ, Rathkopf DE, Gurney H, Jung W, Mason GE, Dibaj S, Wu D, Diorio B, Urtishak K, Del Corral A, Francis P, Kim W, Efstathiou E. Niraparib plus abiraterone acetate with prednisone in patients with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations: second interim analysis of the randomized phase III MAGNITUDE trial. Ann Oncol. 2023 Sep;34(9):772-782. Epub 2023 Jul 1. link to original article link to PMC article PubMed


Docetaxel & Prednisone

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Fizazi et al. 2023 (TRITON3) 2017-02-08 to 2022-02-02 Phase 3 (C) Rucaparib Inferior PFSi (primary endpoint)

Chemotherapy

Endocrine therapy

21-day cycle for up to 10 cycles

References

  1. TRITON3: Fizazi K, Piulats JM, Reaume MN, Ostler P, McDermott R, Gingerich JR, Pintus E, Sridhar SS, Bambury RM, Emmenegger U, Lindberg H, Morris D, Nole F, Staffurth J, Redfern C, Saez MI, Abida W, Daugaard G, Heidenreich A, Krieger L, Sautois B, Loehr A, Despain D, Heyes CA, Watkins SP, Chowdhury S, Ryan CJ, Bryce AH. Rucaparib or Physician's Choice in Metastatic Prostate Cancer. N Engl J Med. 2023 Feb 23;388(8):719-732. Epub 2023 Feb 16. link to original article link to PMC article dosing details in supplement have been reviewed by our editors PubMed NCT02975934


Docetaxel & Prednisolone

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Fizazi et al. 2023 (TRITON3) 2017-02-08 to 2022-02-02 Phase 3 (C) Rucaparib Inferior PFSi (primary endpoint)

Chemotherapy

Endocrine therapy

21-day cycle for up to 10 cycles

References

  1. TRITON3: Fizazi K, Piulats JM, Reaume MN, Ostler P, McDermott R, Gingerich JR, Pintus E, Sridhar SS, Bambury RM, Emmenegger U, Lindberg H, Morris D, Nole F, Staffurth J, Redfern C, Saez MI, Abida W, Daugaard G, Heidenreich A, Krieger L, Sautois B, Loehr A, Despain D, Heyes CA, Watkins SP, Chowdhury S, Ryan CJ, Bryce AH. Rucaparib or Physician's Choice in Metastatic Prostate Cancer. N Engl J Med. 2023 Feb 23;388(8):719-732. Epub 2023 Feb 16. link to original article link to PMC article dosing details in supplement have been reviewed by our editors PubMed NCT02975934


Enzalutamide monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Fizazi et al. 2023 (TRITON3) 2017-02-08 to 2022-02-02 Phase 3 (C) Rucaparib Inferior PFSi (primary endpoint)
de Bono et al. 2020 (PROfound) 2017-04 to 2018-11 Phase 3 (C) Olaparib Seems to have inferior OS

Endocrine therapy

Continued indefinitely

References

  1. PROfound: de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Mehra N, Goessl C, Kang J, Burgents J, Wu W, Kohlmann A, Adelman CA, Hussain M. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 May 28;382(22):2091-2102. Epub 2020 Apr 28. link to original article dosing details in manuscript have been reviewed by our editors link to supplementary appendix PubMed NCT02987543
    1. Update: Hussain M, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Roubaud G, Özgüroğlu M, Kang J, Burgents J, Gresty C, Corcoran C, Adelman CA, de Bono J; PROfound Trial Investigators. Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 Dec 10;383(24):2345-2357. Epub 2020 Sep 20. link to original article PubMed
    2. HRQoL analysis: Thiery-Vuillemin A, de Bono J, Hussain M, Roubaud G, Procopio G, Shore N, Fizazi K, Dos Anjos G, Gravis G, Joung JY, Matsubara N, Castellano D, Degboe A, Gresty C, Kang J, Allen A, Poehlein C, Saad F. Pain and health-related quality of life with olaparib versus physician's choice of next-generation hormonal drug in patients with metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations (PROfound): an open-label, randomised, phase 3 trial. Lancet Oncol. 2022 Mar;23(3):393-405. Epub 2022 Feb 11. Erratum in: Lancet Oncol. 2022 Apr;23(4):e161. link to original article PubMed
  2. TRITON3: Fizazi K, Piulats JM, Reaume MN, Ostler P, McDermott R, Gingerich JR, Pintus E, Sridhar SS, Bambury RM, Emmenegger U, Lindberg H, Morris D, Nole F, Staffurth J, Redfern C, Saez MI, Abida W, Daugaard G, Heidenreich A, Krieger L, Sautois B, Loehr A, Despain D, Heyes CA, Watkins SP, Chowdhury S, Ryan CJ, Bryce AH. Rucaparib or Physician's Choice in Metastatic Prostate Cancer. N Engl J Med. 2023 Feb 23;388(8):719-732. Epub 2023 Feb 16. link to original article link to PMC article dosing details in supplement have been reviewed by our editors PubMed NCT02975934


Olaparib monotherapy

Regimen variant #1, 300 mg twice per day

FDA-recommended dose
Study Dates of enrollment Evidence Comparator Comparative Efficacy
de Bono et al. 2020 (PROfound) 2017-04 to 2018-11 Phase 3 (E-RT-switch-ooc) Physician's choice of:
1a. Abiraterone
1b. Enzalutamide 		Superior rPFS (primary endpoint)
Median rPFS: 7.4 vs 3.6 mo
(HR 0.34, 95% CI 0.25-0.47)

Seems to have superior OS1 (secondary endpoint)
Median OS: 19.1 vs 14.7 mo
(HR 0.69, 95% CI 0.50-0.97)

1Reported efficacy is for patients in Cohort A in the 2020 update.

Prior treatment criteria

  • Progression on abiraterone or enzalutamide

Biomarker eligibility criteria

  • Cohort A: 1+ alterations in BRCA1, BRCA2, or ATM
  • Cohort B: 1+ alterations in BRIP1, BARD1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, or RAD54L

Targeted therapy

Continued indefinitely


Regimen variant #2, 400 mg twice per day

Study Dates of enrollment Evidence
Kaufman et al. 2014 (Study 42) 2010-02-21 to 2012-07-31 Phase 2, fewer than 20 pts in subgroup
Mateo et al. 2015 (TOPARP-A) 2012-07 to 2014-09 Phase 2

Biomarker eligibility criteria

  • Study 42: Germline BRCA1/2 mutations and had progression on hormonal and one systemic therapy
  • TOPARP-A: Patients who were found to have homozygous deletions, deleterious mutations, or both in DNA-repair genes were much more likely to respond to olaparib

Targeted therapy

Continued indefinitely

References

  1. 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 PubMed NCT01078662
  2. TOPARP-A: Mateo J, Carreira S, Sandhu S, Miranda S, Mossop H, Perez-Lopez R, Nava Rodrigues D, Robinson D, Omlin A, Tunariu N, Boysen G, Porta N, Flohr P, Gillman A, Figueiredo I, Paulding C, Seed G, Jain S, Ralph C, Protheroe A, Hussain S, Jones R, Elliott T, McGovern U, Bianchini D, Goodall J, Zafeiriou Z, Williamson CT, Ferraldeschi R, Riisnaes R, Ebbs B, Fowler G, Roda D, Yuan W, Wu YM, Cao X, Brough R, Pemberton H, A'Hern R, Swain A, Kunju LP, Eeles R, Attard G, Lord CJ, Ashworth A, Rubin MA, Knudsen KE, Feng FY, Chinnaiyan AM, Hall E, de Bono JS. DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. N Engl J Med. 2015 Oct 29;373(18):1697-708. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01682772
  3. PROfound: de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Mehra N, Goessl C, Kang J, Burgents J, Wu W, Kohlmann A, Adelman CA, Hussain M. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 May 28;382(22):2091-2102. Epub 2020 Apr 28. link to original article dosing details in manuscript have been reviewed by our editors link to supplementary appendix PubMed NCT02987543
    1. Update: Hussain M, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Roubaud G, Özgüroğlu M, Kang J, Burgents J, Gresty C, Corcoran C, Adelman CA, de Bono J; PROfound Trial Investigators. Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 Dec 10;383(24):2345-2357. Epub 2020 Sep 20. link to original article PubMed
    2. HRQoL analysis: Thiery-Vuillemin A, de Bono J, Hussain M, Roubaud G, Procopio G, Shore N, Fizazi K, Dos Anjos G, Gravis G, Joung JY, Matsubara N, Castellano D, Degboe A, Gresty C, Kang J, Allen A, Poehlein C, Saad F. Pain and health-related quality of life with olaparib versus physician's choice of next-generation hormonal drug in patients with metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations (PROfound): an open-label, randomised, phase 3 trial. Lancet Oncol. 2022 Mar;23(3):393-405. Epub 2022 Feb 11. Erratum in: Lancet Oncol. 2022 Apr;23(4):e161. link to original article PubMed


Rucaparib monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Abida et al. 2020 (TRITON2) 2017 to not reported Phase 2 (RT)
Fizazi et al. 2023 (TRITON3) 2017-02-08 to 2022-02-02 Phase 3 (E-switch-ooc) Physician's choice of:
1a. Abiraterone
1b. Enzalutamide
1c. Docetaxel & Prednisone
1d. Docetaxel & Prednisolone 		Superior PFSi (primary endpoint)
Median PFSi: 10.2 vs 6.4 mo
(HR 0.61, 95% CI 0.47-0.80)

Prior treatment criteria

  • TRITON3: Progression after treatment with a second-generation androgen-receptor pathway inhibitor

Biomarker eligibility criteria

  • TRITON3: 1+ alterations in BRCA1, BRCA2, or ATM

Targeted therapy

28-day cycles

References

  1. TRITON2: Abida W, Patnaik A, Campbell D, Shapiro J, Bryce AH, McDermott R, Sautois B, Vogelzang NJ, Bambury RM, Voog E, Zhang J, Piulats JM, Ryan CJ, Merseburger AS, Daugaard G, Heidenreich A, Fizazi K, Higano CS, Krieger LE, Sternberg CN, Watkins SP, Despain D, Simmons AD, Loehr A, Dowson M, Golsorkhi T, Chowdhury S; TRITON2 investigators. Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration. J Clin Oncol. 2020 Nov 10;38(32):3763-3772. Epub 2020 Aug 14. link to original article dosing details in abstract have been reviewed by our editors link to PMC article PubMed NCT02952534
  2. TRITON3: Fizazi K, Piulats JM, Reaume MN, Ostler P, McDermott R, Gingerich JR, Pintus E, Sridhar SS, Bambury RM, Emmenegger U, Lindberg H, Morris D, Nole F, Staffurth J, Redfern C, Saez MI, Abida W, Daugaard G, Heidenreich A, Krieger L, Sautois B, Loehr A, Despain D, Heyes CA, Watkins SP, Chowdhury S, Ryan CJ, Bryce AH. Rucaparib or Physician's Choice in Metastatic Prostate Cancer. N Engl J Med. 2023 Feb 23;388(8):719-732. Epub 2023 Feb 16. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT02975934


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