FDA Approves Rucaparib in BRCA-Mutated mCRPC

Today, the FDA granted full approval to rucaparib (Rubraca; pharmaand GmbH) for adults with deleterious germline and/or somatic BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC) who have progressed on prior androgen receptor–directed therapy.¹

The decision is based on results from the phase 3 TRITON3 (NCT02975934) trial confirming a significant improvement in radiographic progression-free survival (PFS) compared with the physician’s choice of therapy.

mCRPC is an advanced stage of prostate cancer in which the disease has spread beyond the prostate to other parts of the body, such as the bones, liver, or lungs, and continues to progress despite very low levels of testosterone achieved through hormone‑lowering treatments like androgen‑deprivation therapy.² In mCRPC, cancer cells adapt and grow even when testosterone is suppressed, making the disease harder to control and treat with standard hormonal therapies. Therefore, management typically involves additional systemic treatments to slow progression, manage symptoms, and extend survival.

In the trial, eligible patients were randomly assigned in a 2:1 ratio to receive oral rucaparib at a dose of 600 mg twice daily or physician’s choice of control therapy, consisting of docetaxel or an alternative second-generation androgen receptor–directed agent not previously received.¹

The primary end point was imaging-based PFS, assessed by independent central radiologic review, with analyses conducted in the BRCA-altered subgroup and the overall intention-to-treat population.

Rucaparib demonstrated a statistically significant improvement in radiographic PFS compared with physician’s choice therapy. Among the 302 patients with BRCAm, median radiographic PFS (rPFS) was 11.2 months (95% CI, 9.2-13.8) with rucaparib vs 6.4 months (95% CI, 5.4-8.3) with enzalutamide, abiraterone acetate, or docetaxel (HR, 0.50; 95% CI, 0.36-0.69; P < .0001). Median overall survival (OS) in the BRCAm subgroup was 23.2 months (95% CI, 19.1-25.2) with rucaparib and 21.2 months (95% CI, 18.0-23.1) with control therapy (HR, 0.91; 95% CI, 0.68-1.20), a difference that was not statistically significant.

In an exploratory analysis of the 103 patients (25%) with ATM mutations, rucaparib did not improve outcomes, with an rPFS HR of 0.95 (95% CI, 0.59-1.52) and an OS HR of 1.21 (95% CI, 0.77-1.90), indicating that the observed benefit in the overall population was primarily driven by patients with BRCA alterations.

References

1. FDA grants regular approval to rucaparib for metastatic castration-resistant prostate cancer. FDA. News release. December 17, 2025. Accessed December 17, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-regular-approval-rucaparib-metastatic-castration-resistant-prostate-cancer
2. Scott J. Understanding metastatic castration-resistant prostate cancer. Verywellhealth. April 18, 2025. Accessed December 17, 2025. https://www.verywellhealth.com/metastatic-castration-resistant-prostate-cancer