The US Food and Drug Administration (FDA) has granted approval of rucaparib (Rubraca; Clovis Oncology) for maintenance therapy in patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, specifically in those who are in complete or partial response to platinum-based chemotherapy.
“This FDA approval provides a meaningful advancement for the treatment of women with recurrent ovarian cancer, offering them the potential to reduce their risk of disease progression following platinum-based chemotherapy,” said Clovis Oncology president and CEO Patrick J. Mahaffy, in a press release. “We are grateful that the FDA expedited review of this maintenance treatment indication, so that physicians can begin offering it to appropriate patients beginning today.”
The FDA granted a priority review to rucaparib for this indication in December 2017. The agent was previously approved in December 2016 for the treatment of ovarian cancer specifically associated with BRCA mutations, in women who had received at least two prior chemotherapy regimens. The new approval is granted regardless of BRCA mutation status.
The approval is based on results of the ARIEL3 trial, which were published in September 2017 in the Lancet. In that randomized, double-blind, placebo-controlled, phase III trial, 561 patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who were in complete or partial response to platinum-based chemotherapy were treated with either rucaparib 600 mg orally twice daily (372 patients) or to placebo (189 patients).
In the full patient population, the median progression-free survival (PFS) was 10.8 months with rucaparib, compared with 5.4 months with placebo, for a hazard ratio (HR) of 0.36 (95% CI, 0.30–0.45; P < .0001). In patients with deleterious somatic or germline BRCA mutations, the benefit was larger, with a median PFS with rucaparib of 16.6 months compared with 5.4 months with placebo, for an HR of 0.23 (95% CI, 0.16–0.34; P < .0001). Patients with positive homologous recombination deficiency (HRD) status had a median PFS of 13.6 months with rucaparib, compared with 5.4 months with placebo, for an HR of 0.32 (95% CI, 0.24–0.42; P < .0001).
The FDA also approved a complementary diagnostic test, FoundationFocus CDxBRCA LOH, to determine HRD status.
The most common adverse events associated with rucaparib in the ARIEL3 trial included nausea, fatigue, abdominal pain/distension, rash, and others. In total, 15% of rucaparib patients discontinued therapy due to adverse events, compared with 2% of placebo patients.
Robert L. Coleman, MD, of the University of Texas MD Anderson Cancer Center in Houston, was among the lead investigators of the ARIEL3 trial, and he noted in the press release that the benefit was seen across subgroups regardless of BRCA mutation status. “Both the efficacy and safety results from the ARIEL3 study reinforce the important role of Rubraca in the treatment of recurrent ovarian cancer and expands the treatment options for patients and physicians battling this disease,” he said.