Dr Bryce on the Implications of the Full FDA Approval of Rucaparib in BRCA+ mCRPC

Getting the full approval for rucaparib for advanced prostate cancer is important because it follows up on the [accelerated] approval that rucaparib has had [since 2020].

Alan H. Bryce, MD, interim president and chief clinical officer of City of Hope Cancer Center Phoenix, as well as a professor in the Department of Medical Oncology & Therapeutics Research at City of Hope, discussed the significance of the FDA’s regular approval of rucaparib (Rubraca) for the treatment of adult patients with BRCA mutation–associated metastatic castration-resistant prostate cancer (mCRPC) previously treated with an androgen receptor (AR)–directed therapy.

The FDA’s December 2025 decision followed the May 2020 accelerated approval of rucaparib for the treatment of adult patients with BRCA mutation—associated mCRPC who have been treated with AR-directed therapy and a taxane-based chemotherapy. Crucially, the regular approval now allows for the use of rucaparib prior to taxane-based chemotherapy, Bryce explained.

He noted that after the accelerated approval was supported by response data from the single-arm, phase 2 TRITON2 trial (NCT02952534), the full approval is backed by randomized data from the phase 3 TRITON3 study (NCT02975934). In TRITON2, findings supporting the prior accelerated approval demonstrated that rucaparib generated a confirmed overall response rate of 44% (95% CI, 31%-57%) and a median duration of response that was not evaluable (NE; 95% CI, 6.4 months-NE). Importantly, patients enrolled in TRITON2 were required to have received prior treatment with 1 to 2 prior lines of AR-directed therapy and 1 line of taxane-based chemotherapy in the castration-resistant setting; in TRITON3, prior taxane exposure in this setting was not required.

Data from TRITON3 that supported the regular approval showed that patients harboring BRCA mutations treated with rucaparib (n = 201) experienced a median radiographic progression-free survival of 11.2 months (95% CI, 9.2-13.8) vs 6.4 months (95% CI, 5.4-8.3) for those given physician’s choice of treatment (n = 101; HR, 0.50; 95% CI, 0.36-0.69; P < .0001). The median overall survival values were 23.2 months (95% CI, 19.1-25.2) and 21.2 months (95% CI, 18.0-23.1), respectively (HR, 0.91; 95% CI, 0.68-1.20).

With rucaparib now approved ahead of taxane-based chemotherapy in the metastatic castration-resistant setting, this regular approval expands treatment options for the population of patients harboring BRCA mutations, Bryce concluded.