Prostate cancer, BRCA-mutated

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Laura S. Graham, MD
University of Colorado
Anschutz Medical Campus
Aurora, CO

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Ali Raza Khaki, MD
Stanford University
Palo Alto, CA

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2 regimens on this page
3 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.


Metastatic castration-resistant

Olaparib monotherapy

Regimen Variant #1, 300 mg BID

FDA-recommended dose
Study Years of enrollment Evidence Comparator Comparative Efficacy
de Bono et al. 2020 (PROfound) 2017-2018 Phase 3 (E-RT-ooc) 1. Abiraterone
2. Enzalutamide
Seems to have superior OS1
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 BID

Study Evidence
Kaufman et al. 2014 (Study 42) Phase 2, <20 pts in subgroup
Mateo et al. 2015 (TOPARP-A) 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 contains dosing details in manuscript 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 contains dosing details in manuscript 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 contains dosing details in manuscript 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

Rucaparib monotherapy

Regimen

Study Years of enrollment Evidence
Awaiting publication (TRITON2) 2017-NR Phase 2 (RT)

Note: this study is the basis of FDA approval; however, no dosing details are provided on CT.gov and there are no published manuscripts to date.

Targeted therapy

References

  1. TRITON2: NCT02952534