Enzalutamide + PARP inhibitor rucaparib adds PSA drops—but no clear rPFS/OS win in all-comer 1L mCRPC (CASPAR)

Alliance A031902 (CASPAR; NCT04455750) tested enzalutamide (androgen receptor inhibitor) plus rucaparib (PARP inhibitor) vs enzalutamide + placebo as first-line therapy for metastatic castration-resistant prostate cancer regardless of HRR mutation status, but the Phase III trial stopped early (10/2023) after enrolling just 61 patients (Enz/Ruca n=30; Enz/Plac n=31; ~50% HRR status unknown). PSA declines favored Enz/Ruca (PSA≥50%: 79% vs 45%; PSA≥90%: 60% vs 43%), yet time-to-event outcomes were statistically inconclusive: median rPFS 17.1 vs 11.7 months (HR 0.72, p=0.44), median PFS 17.1 vs 14.2 months (HR 1.13, p=0.81), and OS not reached vs 27.0 months (HR 0.65, p=0.29)—directionally within (not clearly above) what you’d expect from effective AR-pathway therapy alone in chemo-naïve mCRPC (e.g., enzalutamide in PREVAIL had median rPFS ~20 months vs placebo). Grade 3+ anemia was substantially higher with Enz/Ruca (33% vs 3%), with more AE-driven discontinuations (11.5% vs 0%), consistent with the known hematologic tax of PARP/ARPI combinations.