FDA Approves Rucaparib for BRCA-Mutant mCRPC

The FDA approved single-agent rucaparib (Rubraca) for the treatment of patients with BRCA1/2-mutant, recurrent, metastatic castrate-resistant prostate cancer (mCRPC), according to Clovis Oncology, the manufacturer of the PARP inhibitor.

“Standard treatment options for men with mCRPC have been limited to androgen receptor-targeting therapies, taxane chemotherapy, Radium-223 and sipuleucel-T,” said Wassim Abida, M.D., Medical Oncologist, Memorial Sloan Kettering Cancer Center, and Principal Investigator for the TRITON2 study, in a statement. “Rubraca 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 Rubraca in men with mCRPC and these mutations, it represents an important and timely new treatment option for this patient population.”

The approval is based on findings from the international, open-label, phase II TRITON2 trial that included men with mCRPC associated with 1 of 13 homologous recombination repair (HRR) gene alterations. Primary endpoints were confirmed overall response rate (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.

The approval was based off findings from the multi-center, single-arm TRITON2 trial, where the agent proved a 44% overall response rate. Fifty-five percent of patients with a deleterious BRCA mutation experienced a PSA response rate, too.

Trial participants were given 600 mg of rucaparib — a PARP inhibitor – twice a day until radiographic progression or treatment discontinuation.

Common adverse events (AEs) for the BRCA-mutatnt population included: asthenia/fatigue, nausea, anemia, ALT/AST increased, decreased appetite, constipation, rash, thrombocytopenia, vomiting, and diarrhea.

The most common laboratory abnormalities 35% or more of patients; CTCAE Grade 1-4) were increase in ALT, decrease in leukocytes, decrease in phosphate, decrease in absolute neutrophil count, decrease in hemoglobin, increase in alkaline phosphatase, increase in creatinine, increase in triglycerides, decrease in lymphocytes, decrease in platelets, and decrease in sodium.

“The data from the TRITON2 clinical trial supporting the FDA approval of Rubraca in mCRPC have been highly consistent over time, and we are pleased that the FDA has granted an accelerated approval for Rubraca in this third indication,” said Patrick J. Mahaffy, President and CEO of Clovis Oncology. “We are proud to offer Rubraca as a new treatment option to physicians and eligible prostate cancer patients with a deleterious BRCA mutation beginning today.”

“The FDA approval of Rubraca is a significant milestone for patients with metastatic castration-resistant prostate cancer and a deleterious BRCA mutation,” said Howard Soule, Ph.D., Executive Vice President and Chief Science Officer of the Prostate Cancer Foundation.

“Although new treatments for prostate cancer have been approved in recent years, most men living with advanced stages of this disease continue to face a difficult journey with few treatment options.”