Table 3.
Main clinical trials and results of PARP-i in mCRPC patients with a HR mutation.
| PARP-i | Clinical Trial | Phase and Study Type |
Patient Population | Treatment Arm | N pts | Results | Status in February 2022 |
|---|---|---|---|---|---|---|---|
| Olaparib | PROFOUND (NCT02987543) |
Phase 3, randomized | Progression to ≥1 novel HT 1 Cohort A: BRCA1m, BRCA2m, ATMm. Cohort B: other HR. |
Olaparib vs. Enzalutamide or Abiraterone acetate + prednisone |
Cohort A: 245 Cohort B: 142 |
Cohort A: Olaparib > Hormonal therapy in PFS = 7.4 vs. 3.6 mo, HR 0.34; p < 0.0001 OS = 18.5 vs. 15.1 mo, HR 0.64; p = 0.02 ORR = 33% vs. 2% Cohort A + B: Olaparib > Hormonal therapy in PFS = 5.8 vs. 3.5 mo, HR 0.49; p < 0.0001 OS = 17.5 vs. 14.3 mo, HR 0.67 ORR = 22% vs. 4% |
FDA-approved in May 2020 Active, not recruiting |
| KEYNOTE-365 (NCT02861573) | 1b-2, single arm |
mCRPC (molecularly unselected, docetaxel-pretreated) |
Pembrolizumab + Olaparib (Cohort A) |
102 | BRCA+ vs. BRCA - PSA response: 50% vs. 14% ORR: 33% vs. 6% HR+ vs. HR- PSA response: 22% vs. 13% ORR: 8% vs. 3% |
Active, recruiting |
|
| PROpel (NCT03732820) | Phase 3, randomized | mCRPC 1 L treatment after failure of ADT |
Olaparib + Abiraterone Acetate | 796 | rPFS: 24.8 vs. 16.6 months, HR 0.66, p < 0.0001 OS: HR 0.86 ORR: 58.4% vs. 48.1% |
Active, not recruiting |
|
| Rucaparib | TRITON2 (NCT02952534) |
Phase 2, single arm | Progression to 1–2 novel HT 1 AND 1 taxane-based CT |
Rucaparib | 115 BRCAm |
ORR IRR = 43.5% ORR IA = 50.8% PSA RR = 54.8% m-rPFS IRR = 9.0 mo m-rPFS IA = 8.5 mo 12-mo OS = 73.0% |
FDA-approved in May 2020. Completed |
| Talazoparib | TALAPRO-1 (NCT03148795) |
Phase 2, single arm | Progression to ≥1 novel HT AND 1–2 CT regimens (≥1 taxane-based CT) |
Talazoparib | 86 overall population 46 BRCA1/2m 4 PALB2m 18 ATMm |
ORR overall population = 28% ORR BRCA1/2m = 43.9% ORR PALB2m = 33.3% ORR ATMm = 11.8% m-rPFS BRCA1/2m = 9.3 mo m-rPFS PALB2m = 7.4 mo m-rPFS ATMm = 5.5 mo |
Active, not recruiting |
| Niraparib | GALAHAD (NCT02854436) |
Phase 2, single arm | Progression to ≥1 novel HT 1 AND ≥1 taxane-based CT |
Niraparib | 46 BRCA 1/2m 35 non-BRCAm |
BRCA1/2m vs. non-BRCAm ORR = 41% vs. 9% PSA RR = 50% vs. 3% m-rPFS = 8.2 vs. 5.3 mo mOS = 12.6 vs. 14 mo |
Active, not recruiting |
| MAGNITUDE (NCT03748641) | Phase 3, randomized | mCRPC 1 L treatment after failure of ADT |
Niraparib + Abiraterone Acetate | 423 HR patients |
BRCA1/2m vs. non-BRCAm rPFS: 16.6 vs. 10.9 mo, HR 0.53 ORR: 52% vs. 31% HR+ vs. HR- rPFS: 16.5 vs. 13.7 mo, HR 0.73 ORR: 60% vs. 28% |
Active, not recruiting |
HT: hormonal therapy; N: number; pts: patients; BRCA1m: BRCA1 mutation; BRCA2m: BRCA2 mutation; ATMm: ATM mutation; HR: homologous recombination DNA damage response and repair; CT: chemotherapy; PALB2m: PALB2 mutation; PFS: progression-free survival; mo: month; HR: hazard ratio; p: p value; OS: overall survival; ORR: overall response rate; IRR: independent radiology review; IA: investigator assessment; PSA RR: prostate-specific antigen response rate; m-rPFS: median radiological progression-free survival; 12-mo OS: overall survival at 12 months; FDA: Food and Drug Administration. 1 Novel hormonal therapy, e.g.; abiraterone acetate and/or enzalutamide.