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Showed PARP inhibitor plus abiraterone delays progression in first-line mCRPC, with the largest benefit in BRCA-mutant men.
PROpel, trial NCT03732820 sponsored by AstraZeneca and Merck and reported in 2022, showed that adding the PARP inhibitor olaparib to abiraterone delays progression in first-line metastatic castration-resistant prostate cancer regardless of mutation status, with the largest benefit in men with BRCA mutations. It randomised 796 unselected men and met its primary radiographic progression-free survival endpoint, but overall survival was not significantly improved in the whole population, so the FDA restricted approval in 2023 to BRCA-mutant disease while the EMA approved the combination for all comers. OnCo links it to BRCA1 and BRCA2 as targets, to olaparib and abiraterone acetate, and its findings are consistent with MAGNITUDE and TALAPRO-2 in HRR-mutant disease. Whether unselected men gain enough to justify the toxicity is the open question, and labels differ by region.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
796 randomised.
Not significant; larger effect in BRCA-mutant
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Radiographic progression-free survival (investigator), all comersprimary | Olaparib + abiraterone | 399 | 24.8 months | 0.66 (0.54 to 0.81) | <0.001 | link |
| Placebo + abiraterone | 397 | 16.6 months | ||||
| Overall survival, all comers | Olaparib + abiraterone | - | 42.1 months | 0.81 (0.67 to 1) | - | link |
| Placebo + abiraterone | - | 34.7 months |
Shares Prescribe a quarter dose of abiraterone with breakfast, Abiraterone acetate, PARP inhibitors, Olaparib.
Shares MAGNITUDE, Abiraterone acetate, PARP inhibitors, BRCA1 / BRCA2 (HRD).
Shares PROfound, PARP inhibitors, Olaparib, BRCA1 / BRCA2 (HRD).
Shares PARP inhibitors, Olaparib, Metastatic castration-resistant prostate cancer, AstraZeneca.
Shares Prescribe a quarter dose of abiraterone with breakfast, Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test, Abiraterone acetate, AstraZeneca.
Shares Prescribe a quarter dose of abiraterone with breakfast, Abiraterone acetate, Prostate cancer.
Shares Prescribe a quarter dose of abiraterone with breakfast, Abiraterone acetate, Prostate cancer.
Shares Olaparib plus abiraterone versus placebo plus abiraterone in metastatic castration-resistant prostate cancer (PROpel): final prespecified overall survival results of a randomised, double-blind, phase 3 trial, Olaparib, BRCA1 / BRCA2 (HRD), Metastatic castration-resistant prostate cancer.