Analysis of the Phase III ENGOT-OV16/NOVA Study: Niraparib Efficacy in Germline Wild-type Recurrent Ovarian Cancer with Homologous Recombination Repair Defects.

Unlabelled: In this analysis, we examined the relationship between progression-free survival (PFS) and mutation status of 18 homologous recombination repair (HRR) genes in patients in the non-germline -mutated (non-gm) cohort of the ENGOT-OV16/NOVA trial (NCT01847274), which evaluated niraparib maintenance therapy for patients with recurrent ovarian cancer. This exploratory biomarker analysis was performed using tumor samples collected from 331 patients enrolled in the phase III ENGOT-OV16/NOVA trial's non-gm cohort. Niraparib demonstrated PFS benefit in patients with either somatic mutated (sm; HR, 0.27; 95% confidence interval, CI, 0.08-0.88) or wild-type (wt; HR, 0.47; 95% CI, 0.34-0.64) tumors. Patients with wt tumors with other non- HRR mutations also derived benefit from niraparib (HR, 0.31; 95% CI, 0.13-0.77), as did patients with wt/HRRwt (HRR wild-type) tumors (HR, 0.49; 95% CI, 0.35-0.70). When patients with wt/HRRwt tumors were further categorized by genomic instability score (GIS), clinical benefit was observed in patients with homologous recombination-deficient (GIS ≥ 42; HR, 0.33; 95% CI, 0.18-0.61) and in patients with homologous recombination-proficient (HRp; GIS < 42; HR, 0.60; 95% CI, 0.36-0.99) disease. Although patients with sm, other non- HRR mutations, or GIS ≥ 42 benefited the most from niraparib treatment, PFS benefit was also seen in HRp (GIS < 42) patients without HRR mutations. These results support the use of niraparib in patients with recurrent ovarian cancer regardless of /HRR mutation status or myChoice CDx GIS.

Significance: We retrospectively evaluated the mutational profile of HRR genes in tumor samples from 331 patients from the non-germline -mutated cohort of the phase III NOVA trial of patients with platinum-sensitive high-grade serous ovarian cancer. Patients with non- HRR mutations generally benefited from second-line maintenance treatment with niraparib compared with placebo.