Olaparib (PARP inhibitor) + Abiraterone (CYP17 AR-pathway inhibitor) Extends rPFS in Non‑BRCA mCRPC (PROpel)

Olaparib is an oral PARP inhibitor combined with abiraterone, an androgen-biosynthesis (CYP17) inhibitor, and tested in the Phase 3 double-blind PROpel trial (NCT03732820) as first-line therapy for metastatic castration-resistant prostate cancer (mCRPC). In the non-BRCA1/2-mutated subgroup (n=693), investigator-assessed median rPFS was 24.1mo with olaparib+abiraterone vs 19.0mo with placebo+abiraterone (HR 0.76, 95% CI 0.61–0.94), while median OS was 39.6 vs 38.0mo (HR 0.91, 95% CI 0.73–1.13); HRQoL was not significantly different and safety was described as consistent with the overall (biomarker-unselected) PROpel population. Clinically, this looks like an incremental rPFS gain on top of an abiraterone backbone—abiraterone itself improved rPFS to ~13.7mo vs ~8.3mo with prednisone in chemo-naïve mCRPC in COU-AA-302, but cross-trial comparisons to modern mCRPC sequencing are imperfect.