FDA approves rucaparib for chemotherapy-naïve, BRCA-mutated mCRPC

On December 17, 2025, the FDA granted regular approval to rucaparib (Rubraca) for the treatment of adult patients with BRCA mutation (BRCAm)-associated metastatic castration-resistant prostate cancer (mCRPC) who have received prior treatment with an androgen receptor-directed therapy.¹

According to the FDA, patients should be selected for treatment using an FDA-approved companion diagnostic.

The decision today converts the FDA's May 2020 accelerated approval² of rucaparib into a full approval, enabling use of the PARP inhibitor prior to chemotherapy in eligible patients with mCRPC.

"This approval reflects a breakthrough moment for patients and for precision oncology," said Anil D'Souza, CEO of Tolmar, in a news release from the company.³ "For years, oncologists have relied on docetaxel as an important therapy in this setting. Now, TRITON3 has shown that Rubraca can not only move ahead of chemotherapy but outperform it—supported by clear genomic rationale and superior progression-free survival. Bringing Rubraca earlier in the treatment journey offers physicians a more targeted approach for patients with BRCA mutated prostate cancer."

The approval is supported by data from the TRITON3 trial (NCT02975934), in which treatment with rucaparib led to a statistically significant improvement in radiographic progression-free survival (rPFS) compared with physician’s choice of treatment in patients with BRCAm as well as in the overall sample.⁴

In total, the trial enrolled 405 patients who were randomly assigned 2:1 to receive rucaparib or physician’s choice of either an androgen receptor pathway inhibitor (ARPI) that they had not previously received (enzalutamide [Xtandi] or abiraterone acetate) or docetaxel. Approximately 55% of patients in the control arm received docetaxl. Among all patients, 302 had BRCAm and 103 had ATM mutations (ATMm). The trial included patients whose tumors had progressed on a prior ARPI, and all patients were chemotherapy-naïve.

In patients with a BRCAm, the median rPFS was 11.2 months (95% CI, 9.2 to 13.8) with rucaparib vs 6.4 months (95% CI, 5.4 to 8.3) with physician’s choice of treatment (HR, 0.50; 95% CI, 0.36 to 0.69; P < .0001). Data from a subgroup analysis of those with BRCAm showed a rPFS of 11.2 months with rucaparib vs 8.3 months with docetaxel.

Data showed no significant difference in overall survival (OS) between the 2 arms in the all-comer population; data showed a median OS of 23.2 months (95% CI, 19.1 to 25.2) in the rucaparib arm vs 21.2 months (95% CI, 18.0 to 23.1) in the control arm (HR, 0.91; 95% CI, 0.68 to 1.20).

However, in the 103 patients with an ATMm, the hazard ratio for rPFS was 0.95 (95% CI, 0.59 to 1.52) and the hazard ratio for OS was 1.21 (95% CI, 0.77 to 1.90). According to the FDA, the findings from this exploratory analysis indicate “that the overall improvement was primarily attributed to the results seen in patients with BRCAm.”

The safety profile for rucaparib was consistent with the known profile for the agent. Overall, 14.8% of patients in the rucaparib arm vs 21.5% of patients in the control arm discontinued treatment due to treatment-emergent adverse events.

The FDA noted that the recommended dose of rucaparib is 600 mg (two 300 mg tablets) taken orally twice daily with or without food until disease progression or unacceptable toxicity.

REFERENCES

1. FDA grants regular approval to rucaparib for metastatic castration-resistant prostate cancer. News release. US Food & Drug Administration. 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. FDA grants accelerated approval to rucaparib for BRCA-mutated metastatic castration-resistant prostate cancer. News release. US Food & Drug Adminstration. May 15, 2020. Accessed December 17, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-rucaparib-brca-mutated-metastatic-castration-resistant-prostate

3. Tolmar announces expanded indication for Rubraca® (rucaparib) first and only PARP inhibitor to outperform docetaxel in a head-to-head phase 3 trial. News release. Tolmar. December 19, 2025. Accessed December 19, 2025. https://www.prnewswire.com/news-releases/tolmar-announces-expanded-indication-for-rubraca-rucaparib-first-and-only-parp-inhibitor-to-outperform-docetaxel-in-a-head-to-head-phase-3-trial-302646925.html

4. Fizazi K, Piulats JM, Reaume MN, et al. Rucaparib or physician’s choice in metastatic prostate cancer. N Engl J Med. Published online February 16, 2023. doi:10.1056/NEJMoa221467