Listen to the FDA D.I.S.C.O. podcast about this approval.
On December 19, 2016, the U.S. Food and Drug Administration granted accelerated approval to rucaparib (RUBRACA, Clovis Oncology Inc.) for treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with two or more chemotherapies.
In conjunction with the drug approval, FDA approved the FoundationFocus CDxBRCA test (Foundation Medicine Inc.), the first FDA-approved next-generation sequencing (NGS)-based companion diagnostic to identify patients with advanced ovarian cancer eligible for treatment with rucaparib. The test detects alterations in BRCA1 and BRCA2 genes in the tumor tissue of ovarian cancer patients.
Approval of rucaparib and the FoundationFocus CDxBRCA test was based on data from two multicenter, single-arm, open label clinical trials that evaluated the efficacy of rucaparib in 106 patients with advanced ovarian cancer who had progressed after treatment with two or more prior chemotherapies. During enrollment, BRCA1/2 status was determined using either local germline BRCA test results or a Foundation Medicine clinical trial assay. Formalin-fixed paraffin-embedded tumor tissue samples were collected for testing with the companion diagnostic. Tumor BRCA mutation status was verified retrospectively in 96% (64/67) of the patients for whom a tumor tissue sample was available by the FoundationFocus CDxBRCA test.
All 106 patients received rucaparib 600 mg orally twice daily. Objective response rate (ORR) and duration of response (DoR) were assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Investigator-assessed ORR was 54% (57/106; 95% CI: 44-64%). Median DoR for the 57 responders (investigator-assessed) was 9.2 months (95% CI: 6.6, 11.6). ORR (investigator-assessed) was 66% (52/79; 95% CI: 54‑76%) in platinum-sensitive patients, 25% (5/20; 95% CI: 9-49%) in platinum-resistant patientsand 0% (0/7; 95% CI: 0-41%) in platinum-refractory patients. ORR was similar for patients with a BRCA1 gene mutation or BRCA2 gene mutation.
The safety of rucaparib was evaluated in 377 patients with advanced ovarian cancer. The most common adverse reactions (greater than or equal to 20%) experienced by patients were nausea, fatigue (including asthenia), vomiting, anemia, abdominal pain, dysgeusia, constipation, decreased appetite, diarrhea, thrombocytopenia, and dyspnea. Adverse reactions led to dose discontinuation in 10% of patients, most frequently from fatigue/asthenia (2%).
Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) was reported in 2 of 377 (0.5%) patients with ovarian cancer. In addition, AML was reported in 2 (1%)>
The recommended dose and schedule for rucaparib is 600 mg (two 300 mg tablets) taken orally twice daily with or without food.
FDA granted the rucaparib application breakthrough therapy designation, priority review status, and orphan drug designation. This application was approved two months before the PDUFA goal date. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics, available at: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf.
Full prescribing information is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/209115s000lbl.pdf
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).