Platinum-based chemotherapy is commonly used in recurrent ovarian cancer, however cumulative toxicity and lack of a clear treatment benefit limit its use. In a phase 3 trial (ENGOT-OV16/NOVA), the PARP inhibitor Niraparib significantly improved the primary endpoint of progression-free survival compared to placebo. Patients were assigned to cohorts by germline BRCA (gBRCA) mutation status and randomized 2:1 to receive Niraparib (300 mg) or placebo once daily. Median progression-free survival (PFS) with Niraparib compared to placebo was 21.0 vs 5.5 months in the gBRCA mutation cohort (hazard ratio, 0.27; 95% confidence interval [CI], 0.17 to 0.41), 9.3 months vs 3.9 months in the overall non-gBRCA cohort (hazard ratio, 0.45; 95% CI, 0.34 to 0.61) and 12.9 vs 3.8 months in a subgroup of the non-mutation cohort who had homologous recombination DNA repair deficiencies (HRD) (hazard ratio, 0.38; 95% CI, 0.24 to 0.59). Even patients with tumors without HRD benefitted from treatment, although at a lower magnitude (PFS 6.9 months vs 3.8 months; hazard ratio, 0.58; 95% CI, 0.36 to 0.92). Taken together, these results suggest that the biomarkers gBRCA mutations and HRD status, although unable to identify all patients with a benefit from Niraparib treatment, could identify patients with a higher magnitude of benefit.
Mirza MR., et al., N Engl J Med., 375:2154-2164, 2016. DOI: 10.1056/NEJMoa1611310
2. The New England Journal of Medicine: