Scientific Publications by FDA Staff

Clin Cancer Res 2017 Dec 1;23(23):7165-70

FDA approval summary: rucaparib for the treatment of patients with deleterious BRCA mutation-associated advanced ovarian cancer.

Balasubramaniam S, Beaver JA, Horton S, Fernandes LL, Tang S, Horne HN, Liu J, Liu C, Schrieber SJ, Yu J, Song P, Pierce W, Robertson KJ, Palmby TR, Chiu HJ, Lee EY, Philip R, Schuck R, Charlab R, Banerjee A, Chen XH, Wang X, Goldberg KB, Sridhara R, Kim G, Pazdur R

On December 19, 2016, the U.S. Food and Drug Administration granted accelerated approval to rucaparib (RUBRACA, Clovis Oncology, Inc.) for the treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with two or more chemotherapies. FDA also approved the FoundationFocus CDx BRCA test (Foundation Medicine Inc.), the first next-generation sequencing-based companion diagnostic, for identifying patients with advanced ovarian cancer eligible for treatment with rucaparib based on detection of deleterious BRCA1 and/or BRCA2 mutations in tumor tissue. Rucaparib's approval was based primarily on efficacy data from 106 patients with BRCA mutation-associated ovarian cancer who had prior treatment with two or more chemotherapies and safety data from 377 ovarian cancer patients, treated with rucaparib 600 mg orally twice daily on two open-label, single-arm trials. Investigator-assessed objective response rate was 54% (57/106; 95% CI: 44-64%), and median duration of response was 9.2 months (95% CI: 6.6, 11.7). The approved companion diagnostic verified tumor BRCA mutation status retrospectively in 96% (64/67) of patients. Common adverse reactions (>/=20%) to rucaparib were nausea, fatigue, vomiting, anemia, abdominal pain, dysgeusia, constipation, decreased appetite, diarrhea, thrombocytopenia, and dyspnea. This article summarizes the FDA review and data supporting rucaparib's accelerated approval.