FDA Approves Rucaparib for BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer
On December 17, 2025, the US Food and Drug Administration (FDA) approved rucaparib for previously treated patients with deleterious BRCA mutation-associated metastatic castration-resistant prostate cancer (mCRPC), as selected via an FDA-approved companion diagnostic test. This approval was based on results from the TRITON3 study.
In this open-label study, researchers enrolled 405 patients harboring BRCA (n = 302) or ATM (n = 103) mutations who experienced disease progression after androgen pathway inhibitor therapy and had not received chemotherapy in the castration-resistant setting. Patients were randomized 2:1 to receive rucaparib or physician’s choice of enzalutamide, abiraterone acetate, or docetaxel. Patients were stratified based on performance status, presence of hepatic metastases, and mutation type (BRCA1, BRCA2, or ATM). Patients were required to maintain a castrate level of testosterone via treatment with androgen deprivation therapy or prior surgical castration.
The primary end point was radiographic progression-free survival (rPFS) in both the intention-to-treat and BRCA-mutated populations, assessed by independent radiology review. A key secondary end point was overall survival (OS).
At analysis, rucaparib significantly improved rPFS compared with physician’s choice therapy in the intention-to-treat population. In the BRCA-mutated population, median rPFS was 11.2 months in the rucaparib arm and 6.4 months in the physician’s choice arm (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.36 to 0.69; P <.0001). Median OS was 23.2 months and 21.2 months, respectively. In an exploratory subgroup of patients with ATM mutations, rucaparib did not improve rPFS (HR, 0.95) or OS (HR, 1.21).
The recommended dose of oral rucaparib is 600 mg twice daily (two 300-mg tablets) with or without food until disease progression or unacceptable toxicity. Prescribing information includes warnings and precautions for myelodysplastic syndrome/acute myeloid leukemia and embryo-fetal toxicity.
Rucaparib previously received accelerated approval in 2020 for a similar indication in adult patients with BRCA-mutated mCRPC following progression on prior androgen receptor-directed therapy.
Source:
US Food and Drug Administration. Accessed December 17, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-regular-approval-rucaparib-metastatic-castration-resistant-prostate-cancer
