FDA Approves Rucaparib in BRCA-Mutated Metastatic CRPC

The FDA has granted standard approval to rucaparib (Rubraca) for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) harboring germline or somatic BRCA deletions who have received prior androgen receptor-targeted therapy.¹

To be eligible for rucaparib, patients must be identified using an FDA-approved companion diagnostic.

The approval is supported by results from the randomized, open-label phase 3 TRITON3 trial (NCT02975934) which were used to confirm rucaparib’s 2020 accelerated approval in patients with BRCA-mutated recurrent mCRPC.

Rucaparib yielded significant improvement in radiographic progression-free survival (rPFS) as determined by independent central review vs physician’s choice of an androgen receptor pathway inhibitor (ARPI) not previously received by the patient or docetaxel in both patients BRCA-mutated disease and the general population.

Rucaparib demonstrated a median rPFS of 11.2 months (95% CI, 9.2-13.8) compared with 6.4 (95% CI, 5.4-8.3) in the physician’s choice arm (hazard ratio [HR], 0.50; 95% CI, 0.36-0.69; P <.0001).

Median overall survival (OS) was 23.2 months (95% CI, 19.1-25.2) in those who received rucaparib compared with 21.2 months (95% CI, 18.0-23.1) in the physician’s choice arm, although OS did not reach statistical significance (HR, 0.9; 95% CI, 0.68-1.20).

An exploratory analysis revealed that patients with ATM mutations achieved an rPFS HR of 0.95 (95% CI, 0.59-1.52) with an OS HR of 1.21 (95% CI, 0.77-1.90), demonstrating that improvement was primarily attributable to patients with BRCA-mutated disease.

The recommended dose of rucaparib is 600 mg via 2 300-mg tablets taken orally twice daily with or without food.

Of 405 patients with mCRPC in TRITON3, 302 had BRCA mutations and 103 had ATM mutations. Requirement criteria included having received a prior ARPI and having not received chemotherapy in the castration-resistant setting. Patients maintained a castrate level of testosterone from androgen deprivation therapy or previous surgical castration.

Patients were randomized 2:1 to receive either rucaparib or physician’s choice of enzalutamide, abiraterone acetate, or docetaxel. Stratification factors included performance status, presence of hepatic metastases, and mutation type.

Safety of Rucaparib in mCRPC

Per findings published in The New England Journal of Medicine in 2023, the most common adverse events (AEs) reported in patients who received rucaparib were fatigue (61%), nausea (50%), and anemia or decreased hemoglobin (47%).² Likewise, the most common grade 3 or 4 AEs were anemia or decreased hemoglobin (24%), neutropenia or a decreased neutrophil count (7%), and fatigue (7%).

Additional frequent AEs in patients receiving rucaparib included decreased appetite (36%), diarrhea (31%), rash (29%), constipation (27%), increased ALT or AST (27%), vomiting (24%), back pain (22%), and peripheral edema (20%).

No emergent cases of myelodysplastic syndrome or acute myeloid leukemia occurred. In the rucaparib arm, 1 patient had interstitial lung disease, 9 had pulmonary embolism, and 3 had deep-vein thrombosis. In the control arm, 2 patients, both of whom were receiving docetaxel, had pneumonitis; 9 patients had pulmonary embolism; and 1 patient had deep-vein thrombosis.

AEs led to treatment discontinuation in 40 patients (15%) receiving rucaparib and 28 patients (22%) in the control group. AEs led to death in 5 and 3 patients in respective treatment arms.

Deaths in the rucaparib arm were linked with cardiac failure, esophageal perforatiom, myocardial ischemia, sepsis, and a combination of lower repiratory tract infection and ventricular fibrillation. Deaths in the control arm were due to COVID-19, pneumonia, and an unknown cause. AEs leading to death were not linked with trial treatment.

References

1. FDA grants regular approval to rucaparib for metastatic castration-resistant prostate cancer. FDA. 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. Fizazi K, Piulats JM, Reaume MN, et al. Rucaparib or Physician's Choice in Metastatic Prostate Cancer. N Engl J Med. 2023;388(8):719-732. doi:10.1056/NEJMoa2214676