The oral PARP inhibitor niraparib yielded significantly improved progression-free survival for women with platinum-sensitive, recurrent ovarian cancer in a phase III trial.
The oral PARP inhibitor niraparib yielded significantly improved progression-free survival (PFS) for women with platinum-sensitive, recurrent ovarian cancer in a phase III trial, regardless of whether germline BRCA mutations were present or not.
“Despite a high initial response rate to platinum and taxane treatment in patients with advanced cancer, the effectiveness of the treatments diminishes over time, and most patients have a relapse,” wrote study authors led by Mansoor R. Mirza, MD, of Rigshospitalet-Copenhagen University Hospital in Denmark.
Niraparib showed activity in a phase I dose-escalation study in ovarian cancer; the new trial was a randomized, placebo-controlled, phase III trial including 553 patients at 107 sites across the United States, Canada, and various European countries. They were divided based on the presence of BRCA mutations: there were 201 in the mutation cohort, and 345 in the non-BRCA mutation cohort. The results were published online ahead of print in the New England Journal of Medicine, and simultaneously presented at the European Society for Medical Oncology (ESMO) 2016 Congress in Copenhagen.
The median follow-up was 16.9 months in the full intention-to-treat population. PFS was significantly better with niraparib than placebo in all groups. In the BRCA-mutated group, niraparib patients had a median PFS of 21 months, compared with 5.5 months with placebo (hazard ratio [HR], 0.27 [95% CI, 0.17–0.41]; P < .001). The non-mutant group was further divided into those with homologous recombination deficiency (HRD) and those without; in those with HRD, the median PFS was 12.9 months with niraparib and 3.8 months with placebo (HR, 0.38 [95% CI, 0.24–0.59]; P < .001). In the full non-mutant cohort, the PFS rates were 9.3 months with the study drug and 3.9 months with placebo (HR, 0.45 [95% CI, 0.34–0.61]; P < .001).
On secondary endpoint analyses, niraparib offered longer chemotherapy-free intervals than placebo, as well as longer time until first subsequent treatment. Overall survival data were not yet mature at the time of this analysis.
More patients in the niraparib group (14.7%) discontinued treatment due to an adverse event (AE) of any grade than in the placebo group (2.2%). There no on-treatment deaths reported in either group. The most common grade 3/4 AEs with the study drug included thrombocytopenia (33.8%), anemia (25.3%), and neutropenia (19.6%). These were generally well managed with dose modifications.
“The results suggest that niraparib provides significant clinical benefit regardless of BRCA status,” the authors wrote. “Although BRCA mutation status and HRD status may provide important information regarding the magnitude of the potential treatment benefit in a given patient population, these biomarkers do not appear to be sufficiently precise to predict which individual patients … will and will not derive benefit from niraparib treatment.”