FDA Grants Accelerated Approval to Rubraca for Advanced Ovarian Cancer

Treatment indicated for women with specific gene mutation

The FDA has granted accelerated approval to rucaparib (Rubraca, Clovis Oncology) to treat women with a certain type of ovarian cancer. Rucaparib is approved for 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.

The National Cancer Institute estimates that 22,280 women will be diagnosed with ovarian cancer in 2016 and that an estimated 14,240 will die of the disease. Approximately 15% to 20% of patients with ovarian cancer have a BRCA gene mutation.

BRCA genes are involved in 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 slow-down or stoppage of tumor growth.

The FDA also approved the FoundationFocus CDxBRCA (Foundation Medicine, Inc.) companion diagnostic for use with rucaparib, which is the first next-generation-sequencing (NGS)-based companion diagnostic approved by the agency. The NGS 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.

The safety and efficacy of rucaparib were assessed in two single-arm studies involving 106 participants with BRCA-mutated advanced ovarian cancer who had been treated with two 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 studies measured the percentage of participants who experienced complete or partial shrinkage of their tumors (the overall response rate). Fifty-four percent of the participants who received rucaparib in the two studies experienced complete or partial shrinkage of their tumors lasting a median period of 9.2 months.

Common adverse effects of treatment with rucaparib include nausea, fatigue, vomiting, anemia, abdominal pain, dysgeusia, constipation, decreased appetite, diarrhea, thrombocytopenia, and dyspnea. Rucaparib is associated with risks for serious adverse events, such as myelodysplastic syndrome, acute myeloid leukemia, and fetal harm.

The FDA approved rucaparib under its accelerated development program, which allows approval of a drug to treat a serious or life-threatening disease or condition based on clinical data showing that the drug has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit. Previously, the FDA granted rucaparib a breakthrough therapy designation, priority review status, and orphan drug status.

Source: FDA; December 19, 2016.