FDA recently approved rucaparib (Rubraca, Clovis Oncology) tablets to treat patients with deleterious BRCA mutation (germline and/or somatic)-associated advanced ovarian cancer, who have been treated with 2 or more chemotherapies.
“Recurrent ovarian cancer remains one of the most difficult cancers to treat and, for so many years, medical advances in this space have been limited,” said Robert L. Coleman, MD, professor and deputy chairman, vice chair, clinical research, Ann Rife Cox chair in gynecology at the University of Texas MD Anderson Cancer Center in Houston and one of the principal investigators in the ARIEL clinical trial program. “Today’s approval of Rubraca for the treatment of advanced ovarian cancer demonstrates the value of treatment with PARP inhibitors and represents an important advance for women diagnosed with either germline or somatic BRCA-mutated tumors who have been treated with two or more chemotherapies.”
Rubraca’s indication is approved under FDA’s accelerated approval program, and is based on objective response rate and duration of response results from 2 multicenter single-arm, open-label clinical trials, Study 10 and ARIEL2 Parts 1 and 2. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
The approval is an “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 the disease. In addition, approximately 15% to 20% of patients with ovarian cancer have a BRCA gene mutation.
In the 2 Ariel studies, all 106 patients received Rubraca orally 600 mg twice daily as monotherapy until disease progression or unacceptable toxicity. Response assessment by independent radiology review (IRR) was 42%, with a median duration of response (DOR) of 6.7 months. Investigator-assessed objective response rate (ORR) was 66% in platinum-sensitive patients, 25% in platinum-resistant patients and 0% in platinum-refractory patients. ORR was similar for patients with a BRCA1 gene mutation or BRCA2 gene mutation.
The most common adverse reactions were nausea, asthenia/fatigue, vomiting, anemia, constipation, dysgeusia, decreased appetite, diarrhea, abdominal pain, thrombocytopenia and dyspnea. The most common laboratory abnormalities were increase in creatinine, increase in ALT, increase in AST, decrease in hemoglobin, decrease in lymphocytes, increase in cholesterol, decrease in platelets and decrease in absolute neutrophil count.
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