The U.S. Food and Drug Administration (FDA) today granted accelerated approval to rucaparib (Rubraca) to treat women with advanced ovarian cancer who have been treated with two or more chemotherapies and whose tumors have a specific gene mutation (deleterious BRCA) as identified by an FDA-approved companion diagnostic test. Today, the FDA also approved the FoundationFocus CDxBRCA companion diagnostic for use with rucaparib, which is the first next-generation sequencing–based companion diagnostic approved by the agency. The next-generation sequencing test detects the presence of deleterious BRCA gene mutations in the tumor tissue of ovarian cancer patients. If one or more of the mutations are detected, the patient may be eligible for treatment with rucaparib.
“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,” said 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. “Women with these gene abnormalities who have tried at least two chemotherapy treatments for their ovarian cancer now have an additional treatment option.”
The National Cancer Institute estimates that 22,280 women will be diagnosed with ovarian cancer in 2016, and an estimated 14,240 will die of this disease. Approximately 15% to 20% of patients with ovarian cancer have a BRCA gene mutation.
BRCA genes are involved with repairing damaged DNA and normally work to prevent tumor development. However, mutations of these genes may lead to certain cancers, including ovarian cancers. Rucaparib is a poly ADP-ribose polymerase (PARP) inhibitor that blocks an enzyme involved in repairing damaged DNA. By blocking this enzyme, DNA inside the cancerous cells with damaged BRCA genes may be less likely to be repaired, leading to cell death and possibly a slowdown or stoppage of tumor growth.
The safety and efficacy of rucaparib were studied in two, single-arm clinical trials involving 106 participants with BRCA-mutated advanced ovarian cancer who had been treated with 2 or more chemotherapy regimens. BRCA gene mutations were confirmed in 96% of tested trial participants with available tumor tissue using the FoundationFocus CDxBRCA companion diagnostic.
The trials measured the percentage of participants who experienced complete or partial shrinkage of their tumors (ie, overall response rate). Fifty-four percent of the participants who received rucaparib in the trials experienced complete or partial shrinkage of their tumors lasting a median of 9.2 months.
Common side effects of rucaparib include nausea, fatigue, vomiting, anemia, abdominal pain, dysgeusia, constipation, decreased appetite, diarrhea, thrombocytopenia, and dyspnea. Rucaparib is also associated with serious risks, such as myelodysplastic syndromes, acute myeloid leukemia, and fetal harm.
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