Rucaparib vs. Standard-of-Care Therapies in Metastatic, Castration-Resistant Prostate Cancer

Based on practice-changing evidence, many patients with metastatic, castration-sensitive prostate cancer receive androgen deprivation therapy (ADT) intensification with agents such as abiraterone acetate, apalutamide, enzalutamide and docetaxel. As a consequence of both the earlier integration of these agents in the treatment course and the lack of prospective evidence regarding drug sequencing, the management of patients with metastatic, castration-resistant prostate cancer (MCRPC) is increasingly challenging.

Investigators conducted an industry-sponsored phase 3 study comparing rucaparib to physician's choice of therapy (docetaxel, abiraterone acetate, or enzalutamide) in men with MCRPC with BRCA or ATM alterations. Eligible patients had disease progression after treatment with a second-generation androgen receptor pathway inhibitor (ARPI); previous treatment with a taxane chemotherapy was permitted. Crossover to rucaparib at time of progression was permitted. Of 405 patients who underwent randomization (2:1), approximately 75% had a BRCA alteration and 22% had received prior docetaxel.

At a median 62 months of follow-up, imaging-based progression-free survival (PFS) — the primary outcome — was significantly longer in the rucaparib arm than the standard-of-care arm both in the BRCA subgroup (median, 11.2 vs. 6.4 months; hazard ratio, 0.50; P<0.001) and in the intention-to-treat population (median, 10.2 vs. 6.4 months; HR 0.61; P<0.001). An exploratory analysis of patients with ATM alterations showed no statistical difference in PFS between treatment arms. Side effects from all treatments were consistent with previous reports.