FDA Approves Rucaparib for Adult Patients with BRCA+ mCRPC

The FDA approved rucaparib for the treatment of adult patients with a deleterious BRCA mutation-associated metastatic castration-resistant prostate cancer.

The FDA approved rucaparib (Rubraca) for the treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy. 

This indication was approved under accelerated approval based on the objective response rate (ORR) and duration of response (DOR) data observed in the multi-center, single arm TRITON2 clinical trial.

“Standard treatment options for men with mCRPC have been limited to androgen receptor-targeting therapies, taxane chemotherapy, Radium-223 and sipuleucel-T,” Wassim Abida, MD, medical oncologist at Memorial Sloan Kettering Cancer Center and principal investigator for the TRITON2 study, said in a press release. “[Rucaparib] is the first in a class of drugs to become newly available to patients with mCRPC who harbor a deleterious BRCA mutation. Given the level and duration of responses observed with [rucaparib] in men with mCRPC and these mutations, it represents an important and timely new treatment option for this patient population.”

In the international, multicenter, open-label study, investigators enrolled male patients with mCRPC associated with 1 of 13 homologous recombination repair (HRR) gene alterations. Patients had disease progression on androgen-receptor directed therapy and 1 prior taxane-based chemotherapy. In addition, they had an ECOG performance status of 0 or 1 and could not have received a prior PARP inhibitor, mitoxantrone, cyclophosphamide, or platinum-based chemotherapy. 

Participants in the study were treated with 600 mg of rucaparib twice daily until radiographic progression or treatment discontinuation. Tumors were radiographically assessed every 8 weeks of 24 weeks, and every 12 weeks thereafter. Moreover, prostate-specific antigen (PSA) assessments were performed every 4 weeks.  

The primary endpoints of the trial include confirmed ORR per RECIST/Prostate Cancer Clinical Trials Working Group 3 criteria in patients with measurable disease at baseline and PSA response in patients with no measurable disease at baseline.

Those who were evaluable for PSA response included 45 patients with BRCA1/2 mutations, and the evaluable population for radiographic response included 25 patients with BRCA1/2 mutations. Prior therapies included abiraterone acetate (Zytiga; 55.6%), enzalutamide (Xtandi; 73.3%), both abiraterone and enzalutamide (31.1%), docetaxel (95.6%), cabazitaxel (Jevtana; 8.9%), sipuleucel-T (Provenge; 13.3%), and radium-223 dichloride (Xofigo; 11.1%).

Findings from the study, which were presented at the 2019 ESMO Congress, included a median follow-up of 13.1 months (range, 4.1-28.5). Results showed that rucaparib elicited a 43.9% confirmed ORR and a confirmed PSA response of 52.0% in patients with mCRPC and a BRCA1/2 mutation. Responses were durable, with 60% of responses lasting ≥24 weeks.

All-grade treatment-emergent adverse events found to occur in >20% of patients were asthenia/fatigue (55.3%), nausea (49.5%), anemia/decreased hemoglobin (37.9%), decreased appetite (27.9%), transient increased aspartate transaminase/alanine aminotransferase (24.7%), constipation (24.7%), vomiting (22.1%), and diarrhea (21.1%). 

Continued approval by the FDA for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. The TRITON3 trial is anticipated to serve as the confirmatory study for the accelerated approval of rucaparib in mCRPC. 

The ongoing, multicenter, randomized phase III TRITON3 trial is comparing single-agent rucaparib with physician’s choice of abiraterone acetate, enzalutamide, or docetaxel in men with mCRPC and homologous recombination deficiency whose disease has progressed on prior treatment. 

Rucaparib was previously approved as a monotherapy for the maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a CR or PR to platinum-based chemotherapy. It was also approved for the treatment of patients with deleterious BRCA mutation-germline and/or somatic-associated epithelial ovarian, fallopian tube, or primary peritoneal cancer who have been treated with ≥2 chemotherapies and selected for therapy based on an FDA-approved companion diagnostic.


Rubraca® (Rucaparib) Approved in the U.S. as Monotherapy Treatment for Patients with BRCA1/2-Mutant, Metastatic Castration-Resistant Prostate Cancer (mCRPC) Who Have Been Treated with Androgen Receptor-Directed Therapy and a Taxane-Based Chemotherapy [news release]. Boulder, Colorado. Published May 15, 2020. businesswire.com/news/home/20200515005527/en/Rubraca®-Rucaparib-Approved-U.S.-Monotherapy-Treatment-Patients. Accessed May 15, 2020.