Rucaparib (PARP inhibitor) extends rPFS in BRCA-mutant mCRPC regardless of when prior ARPI was used

Rucaparib is an oral PARP inhibitor evaluated in the Phase 3 TRITON3 trial (NCT02975934) versus physician’s choice of docetaxel or an ARPI (abiraterone/enzalutamide) in BRCA1/2-mutated mCRPC after progression on 1 prior second-generation ARPI (any setting). In this post-hoc subgrouping by where the prior ARPI was given, rucaparib improved median rPFS vs physician’s choice both after prior ARPI in mCSPC (n=68: 13.6 vs 8.2 months; HR 0.60 [95% CI, 0.32–1.15]) and after prior ARPI in mCRPC (n=234: 11.2 vs 5.8 months; HR 0.43 [95% CI, 0.30–0.61]); median OS was similar in both settings (mCSPC: 23.2 vs 21.7 months; HR 0.81; mCRPC: 23.2 vs 21.0 months; HR 0.91) with comparable treatment-related AE rates (89.6% vs 86.1%). In practical SOC terms, this is consistent with the core TRITON3 message that rucaparib’s rPFS advantage in BRCA1/2-mutated, post-ARPI, chemo-naïve mCRPC generally beats ARPI “switch” and is competitive with docetaxel control performance in this trial, while OS remains hard to move in crossover-permitted designs.