FDA grants regular approval to rucaparib for metastatic castration-resistant prostate cancer
Regulatory approval: On Dec 17, 2025, the FDA approved rucaparib (Rubraca) for adults with deleterious germline and/or somatic BRCA mutation–associated metastatic castration-resistant prostate cancer (mCRPC) previously treated with an androgen receptor–directed therapy. Selection requires an FDA-approved companion diagnostic. Approval was supported by the confirmatory TRITON3 trial showing improved radiographic progression-free survival versus physician’s choice in BRCA-mutant disease; overall survival was not significantly different.
FDA approval (Dec 17, 2025)
The FDA approved rucaparib (Rubraca; pharmaand GmbH) for adults with deleterious BRCA mutation (germline and/or somatic)–associated metastatic castration-resistant prostate cancer (mCRPC) previously treated with an androgen receptor–directed therapy. Patients should be selected using an FDA-approved companion diagnostic. Rucaparib previously received accelerated approval in 2020 for a similar indication.
Supporting evidence: TRITON3 (NCT02975934)
TRITON3 was a randomized, open-label confirmatory trial enrolling 405 patients with mCRPC: 302 BRCA-mutant and 103 ATM-mutant. Patients had progressed on a prior androgen receptor pathway inhibitor and could not have received chemotherapy in the castration-resistant setting. Randomization (2:1) compared rucaparib vs physician’s choice of an alternate ARPI (enzalutamide or abiraterone acetate) or docetaxel.
Primary endpoint: radiographic progression-free survival (rPFS) by independent review.
In BRCA-mutant patients (n=302), median rPFS was 11.2 months with rucaparib vs 6.4 months with physician’s choice (HR 0.50, 95% CI 0.36–0.69; p<0.0001). Median overall survival was 23.2 vs 21.2 months (HR 0.91, 95% CI 0.68–1.20; not significant). Exploratory analyses in ATM-mutant patients showed limited rPFS benefit (HR 0.95).
Safety and dosing
Label warnings include myelodysplastic syndrome/acute myeloid leukemia and embryo-fetal toxicity. Recommended dose: 600 mg orally twice daily (1,200 mg/day) until progression or unacceptable toxicity.