Dr Sokolova on Rucaparib vs Physician’s Choice Therapy in BRCA+ mCRPC

Alexandra Sokolova, MD, assistant professor of medicine, Division of Hematology/Medical Oncology, School of Medicine, Oregon Health & Science University, discusses the evaluation of rucaparib (Rubraca) vs physician’s choice standard of care therapy in patients with BRCA-positive metastatic castration-resistant prostate cancer (mCRPC).

The phase 3 TRITON3 trial (NCT02975934) enrolled chemotherapy-naïve men who were treated with 1 prior line featuring a second-generation androgen receptor pathway inhibitor (ARPI) for their mCRPC, Sokolova begins. Patients were randomly assigned to receive treatment with rucaparib or physician’s choice of therapy, including docetaxel or another second-generation ARPI with abiraterone acetate (Zytiga) or enzalutamide (Xtandi).

Data presented at the 2023 Genitourinary Cancers Symposium showed that the study met its primary end point of radiographic progression-free survival (rPFS). There was an improved rPFS both in those with BRCA-mutant mCRPC, as well as in the intention-to-treat (ITT) population, which included patients who harbored ATM mutations, Sokolova continues. In the ITT population, the rPFS was 10.2 months (95% CI, 8.3-11.2) with rucaparib compared with 6.4 months (95% CI, 5.6-8.2) in patients treated with physician's choice (HR, 0.61; 95% CI, 0.47-0.80; P < .001). Additionally, in patients with BRCA-mutant mCRPC, the median rPFS was 11.2 months (95% CI, 9.2-13.8) with rucaparib compared with 6.4 months (95% CI, 5.4-8.3) with physician’s choice of therapy.

Because chemotherapy was an option in the standard-of-care arm, it allowed investigators to evaluate whether docetaxel or rucaparib provided more benefit in this setting, Sokolova says, adding that rucaparib elicited an improved rPFS compared with docetaxel in the BRCA-mutant population.

In May 2020, the FDA granted accelerated approval to rucaparib for the treatment of adult patients with BRCA mutation (germline and/or somatic)—associated mCRPC who have been treated with AR-directed therapy and a taxane-based chemotherapy. TRITON3 helped confirm prior data that supported the accelerated approval for BRCA-mutated mCRPC and provided more insight on those with ATM mutations, Sokolova concludes.