Rucaparib Approved with a Companion Diagnostic Test for Patients with Advanced Ovarian Cancer

TON - January 2017, Vol 10, No 1 - FDA News & Updates

On December 19, 2016, the FDA granted accelerated approval to rucaparib (Rubraca; Clovis Oncology Inc), a poly ADP-ribose polymerase inhibitor, for the treatment of patients with advanced ovarian cancer whose tumors have deleterious BRCA gene mutation, and who have been treated with ≥2 chemotherapies. The administration also concurrently approved a companion diagnostic test, FoundationFocus CDxBRCA (Foundation Medicine Inc), which is the first next-generation sequencing diagnostic test for this population of patients.

Through an assessment of tumor tissue, the FoundationFocus CDxBRCA test identifies variations in BRCA1 and BRCA2 genes, and pinpoints patients with advanced ovarian cancer who are eligible for treatment with rucaparib. It is recommended that rucaparib 600 mg be administered orally 2 times a day, with or without food.

Data from 2 multicenter, open-label clinical trials were the basis for the FDA’s approval of the drug and companion diagnostic test. The efficacy of rucaparib was evaluated in 106 patients with advanced ovarian cancer whose disease had progressed after receiving treatment with ≥2 chemotherapies. All participants were given oral rucaparib 600 mg twice daily, and had their objective response rate (ORR) and duration of response measured in accordance with the Response Evaluation Criteria in Solid Tumors 1.1 by a designated investigator.

Results showed that 54% (n = 57) of patients achieved an ORR, and their median duration of response was 9.2 months. Patients also had their ORR measured after being categorized based on their status as platinum-resistant (ORR, 25%), platinum-refractory (ORR, 0%), or platinum-sensitive (ORR, 66%).

Although the status of BRCA1 and BRCA2 gene mutations was determined during study enrollment with local germline BRCA tests or a clinical trial assay, tissue samples were collected for use with the FoundationFocus CDxBRCA diagnostic test. A total of 67 patients had tumor tissue samples available for use with the companion diagnostic test; tumor BRCA mutations were verified in 96% (n = 64) of these patients.

Of note, the trial results showed that the ORR was similar for patients regardless of whether they had a BRCA1 or BRCA2 gene mutation.

An assessment of the safety of rucaparib was also conducted in 377 patients with advanced ovarian cancer. Nausea, fatigue, dysgeusia, diarrhea, anemia, abdominal pain, dyspnea, vomiting, decreased appetite, constipation, and thrombocytopenia were the most common adverse events reported in patients using the drug. Fatigue and other adverse events led to discontinuation of rucaparib in 10% of patients.

The FDA stresses the need to monitor patients receiving rucaparib for hematology toxicity at the time of initiation and every month thereafter, and requests that all serious adverse events associated with use of the drug or its companion diagnostic test be reported by healthcare professionals to the FDA’s MedWatch Reporting System. Rucaparib should be discontinued in patients with a confirmed diagnosis of myelodysplastic syndrome/acute myeloid leukemia.

Last modified: February 2, 2017