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FDA grants breakthrough therapy designation to rucaparib for advanced ovarian cancer
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The FDA today granted breakthrough therapy designation to rucaparib as monotherapy for patients with advanced ovarian cancer, according to a press release from the drug’s manufacturer.
Rucaparib (Clovis Oncology) is an oral, small-molecule PARP inhibitor developed for the treatment of platinum-sensitive ovarian cancer, specifically in patients with tumors that have BRCA mutations and other DNA deficiencies commonly referred to as “BRCA-like.”
The FDA based its decision on efficacy and safety results from two ongoing phase 2 studies of rucaparib in ovarian cancer — the ARIEL2 study and a study that included women with germline BRCA mutations.
An update from ARIEL2, presented last month at the Annual Meeting on Women’s Cancer, showed 65% of evaluable patients with BRCA mutations achieved a RECIST response, and 70% achieved a RECIST and/or CA-125 response. Researchers identified responses in germline and somatic BRCA-mutant tumors.
Rucaparib activity was higher for patients with prospectively defined BRCA-like homologous recombination deficiency signature compared with biomarker-negative patients. Of the patients with the BRCA-like signature, 48% achieved a RECIST and/or CA-125 response and 40% achieved a RECIST response. Only one of 13 biomarker-negative patients (8%) achieved a RECIST and/or CA-125 response.
An ARIEL2 extension study is expected to include about 300 women. The randomized ARIEL3 trial will compare rucaparib vs. placebo in approximately 540 women with platinum-sensitive high-grade ovarian, fallopian tube or primary peritoneal cancer.
Robert L. Coleman
“Women with ovarian cancer are in need of better therapeutic options, and there is great focus on the potential of PARP inhibitors. Data presented to date in mutant BRCA patients treated with rucaparib are very encouraging, as is the breakthrough therapy designation conferred by the FDA,” Robert L. Coleman, MD, vice chair of clinical research and the Ann Rife Cox chair in gynecology at The University of Texas MD Anderson Cancer Center and one of the two principal investigators of the ARIEL3 study, said in the press release. “I am very enthusiastic about the substantive progress made by Clovis with both rucaparib and its patient selection tool that appears to be moving beyond BRCA to efficiently identify responder versus non-responder populations. Continuing successful development of this drug and its companion diagnostic will be a huge advance for women with this disease. Importantly, these data suggest that the majority of women tested might benefit from rucaparib treatment.”
Rucaparib also proved to be highly tolerable, with treatment-related adverse events occurring in 15% of patients. Those events — primarily grade 1 or grade 2 — included nausea, fatigue, transient ALT/AST elevations, dysgeusia, constipation, decreased appetite, vomiting and diarrhea. The only common grade 3 or grade 4 toxicity was anemia/low hemoglobin.
Additional data from ARIEL2 will be presented at the ASCO Annual Meeting, scheduled for May 29 to June 2 in Chicago. – by Anthony SanFilippo