First NGS-Based Companion Diagnostic Approved With Rucaparib for Advanced Ovarian Cancer

Women with advanced ovarian cancer that harbors a deleterious BRCA mutation and who have failed on at least 2 chemotherapy regimens can be treated with Clovis Oncology’s rucaparib (Rubraca), the FDA has announced.

Of the more than 22,000 women diagnosed with ovarian cancer each year, about 15% to 20% have a BRCA gene mutation. This results in faulty DNA repair pathways, which can promote tumor development. Rucaparib inhibits the enzyme poly ADP-ribose polymerase (PARP) that is involved in DNA damage repair—PARP inhibition in the cancer cells can prevent tumor growth.

Clovis submitted results from 2 single-arm clinical trials in 106 patients with ovarian cancer who had failed on 2 or more chemotherapy treatments. BRCA mutation in the ovarian tumor was confirmed in 96% of patients. A pooled analysis of the data confirmed a complete response rate of 9% and a partial response rate of 45%; the median duration of response was 9.2 months. Disease progression was observed in 9 patients.

“Today’s approval is another example of the trend we are seeing in developing targeted agents to treat cancers caused by specific mutations in a patient’s genes," Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research and acting director of the FDA’s Oncology Center of Excellence, said in a statement. "Women with these gene abnormalities who have tried at least two chemotherapy treatments for their ovarian cancer now have an additional treatment option.”

Along with this approval, the FDA has also approved the first next-generation sequencing—based companion diagnostic test for Rubraca, FoundationFocus CDxBRCA.

The most common side effects associated with rucaparib are nausea, fatigue, vomiting, anemia, abdominal pain, dysgeusia, constipation, decreased appetite, diarrhea, thrombocytopenia, and dyspnea. The drug is also associated with serious risks, such as myelodysplastic syndrome, acute myeloid leukemia, and fetal harm.