FDA Approves Rubraca®, First PARP Inhibitor for Prostate Cancer

The U.S. Food and Drug Administration (FDA) granted accelerated approval to Rubraca® (rucaparib) for the treatment of patients with deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (CRPC) who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy. This is the first poly ADP ribose polymerase (PARP) inhibitor approved to treat prostate cancer.

The decision was based on results of the ongoing, multicenter, single-arm TRITON2 study that included 115 patients with BRCA-mutated (germline and/or somatic) metastatic CRPC who had been treated with androgen receptor-directed therapy and taxane-based chemotherapy. Patients received rucaparib 600 mg orally twice daily and concomitant GnRH analog or had prior bilateral orchiectomy.

Response observed with rucaparib

The objective response rate (ORR) and duration of response (DOR) were assessed in 62 patients with measurable disease. The confirmed ORR was 44% (95% CI, 31-57), and median DOR was not evaluable (95% CI, 6.4 to not evaluable). DOR ranged from 1.7 to more than 24.0 months. Fifteen of 27 patients (56%) with confirmed objective responses had a DOR of six or more months.

The most common adverse events associated with rucaparib were fatigue, nausea, anemia, increased alanine transaminase/aspartate transaminase, decreased appetite, rash, constipation, thrombocytopenia, vomiting, and diarrhea.

A confirmatory randomized, open-label, phase III TRITON3 trial is currently underway, comparing rucaparib versus physician’s choice in patients with metastatic CRPC who have specific gene alterations, including BRCA and ATM alterations, and have experienced disease progression after androgen receptor-directed therapy but have not received chemotherapy.

Rucaparib is already FDA-approved to treat BRCA-mutated ovarian cancer, as well as maintenance therapy for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.