The FDA has approved Rubraca (rucaparib), a poly (ADP-ribose) polymerase inhibitor, to treat recurring epithelial ovarian, fallopian tube, or primary peritoneal cancers in patients receiving platinum-based chemotherapy with complete or fractional treatment responses.
The basis for drug approval was determined by results from ARIEL3, a randomized, double-blind, clinical trial conducted with 561 eligible cancer patients. Epithelial ovarian, fallopian tube, and primary peritoneal cancer patients with previous platinum-based chemotherapies were either administered a placebo (n=189) or twice-daily rucaparib (600 mg) orally (n=372) until adverse effects such as disease exacerbation or toxicity were reported.
Next-generation sequencing revealed whether tumor samples had either somatic or germline mutations for BRCA (tBRCA), as well as the percentage of heterozygotic genome lost (LOH). Patients testing positive for tBRCA and high LOH were categorized with positive homologous recombination deficiency (HRD).
Median progression-free survival rates for all patients, HRD subgroup patients, and tBRCA subgroup patients taking rucaparib compared with placebo had a hazard ratio (HR) 0.36, 0.32, and 0.23, respectively.
Some of the most prevalent adverse events in patients taking Rubraca (Clovis Oncology Inc) were nausea, fatigue, abdominal pain, rash, dysgeusia, anemia, vomiting, and decreased appetite. These events occurred in more than 20% of patients taking rucaparib and 15% discontinued treatment.
“The FDA also concurrently approved the complementary diagnostic test, FoundationFocus CDx BRCA LOH, for tumor samples to determine HRD status,” according to the report. “The recommended rucaparib dose is 600 mg (two 300 mg tablets) taken orally twice daily with or without food.”
FDA approves rucaparib for maintenance treatment of recurrent ovarian, fallopian tube, or primary peritoneal cancer [press-release]. US Food & Drug Administration. April 6, 2018. Accessible at: https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm603997.htm