Prostate cancer, BRCA-mutated
Revision as of 07:08, 18 July 2023 by Warner-admin (talk | contribs) (Text replacement - ", <20 p" to ", fewer than 20 p")
7 regimens on this page
8 variants on this page
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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 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 |
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
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
References
- 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
- 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
- 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
- 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
- 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-NR | Phase 2 (RT) | |||
| Fizazi et al. 2023 (TRITON3) | NR in abstract | Phase 3 (E-switch-ooc) | Physician's choice of: 1a. Abiraterone 1b. Enzalutamide 1c. Docetaxel |
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
References
- 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 contains dosing details in abstract link to PMC article PubMed NCT02952534
- 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 PubMed NCT02975934