Worldwide, ovarian cancer (OC) accounts for 314,000 diagnoses and >207,000 deaths annually [1]. No screening tests exist, and approximately 75% of women present with advanced-stage disease [2,3]. High-grade serous carcinoma (HGSC), the most common OC pathology, is often initially responsive to platinum-based chemotherapy (PBCT), and 50% of HGSCs exhibit underlying homologous recombination deficiency (HRD) through mutations in BRCA1, BRCA2, or other genomic changes [3]. Despite initial chemotherapy sensitivity, most patients experience recurrence, necessitating additional treatment. Re-use of PBCT can achieve a response if the tumor is platinum sensitive, but treatment efficacy lessens with each subsequent relapse [4].

Poly(ADP-ribose) polymerase (PARP) enzymes play critical roles in DNA single-strand break repair via multiple pathways, including homologous recombination [3,5]. PARP inhibition results in aggregation of double-stranded DNA breaks, ultimately inducing cell death; use of PARP inhibitors has significantly affected maintenance therapy for advanced HGSCs [5]. Niraparib is a potent and selective oral PARP inhibitor initially approved by the US Food and Drug Administration (FDA) in 2017 as maintenance treatment in adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer (collectively referred to as “OC”) after a complete or partial response to PBCT [6] and by the European Medicines Agency (EMA) in 2017 as maintenance treatment of adult patients with platinum-sensitive relapsed high-grade serous epithelial OC after a complete or partial response to PBCT [7]. In 2022, FDA approval of niraparib as second-line maintenance therapy was amended to include only patients with deleterious or suspected deleterious germline BRCA (gBRCA) mutations [8]. EMA approval remains unchanged [7].

Initial approval in platinum-sensitive recurrent OC was based on the randomized, double-blind, placebo-controlled phase 3 ENGOT-OV16/NOVA (NCT01847274) trial data, in which niraparib maintenance treatment was compared with placebo in 2 independent patient cohorts, based on gBRCA mutation status (gBRCA-mutated [gBRCAm] versus non-gBRCAm). In the primary analysis, niraparib demonstrated statistically significant improvement in progression-free survival (PFS) in both cohorts [9]. Median PFS for niraparib and placebo in the gBRCAm group was 21 and 5.5 months, respectively (hazard ratio [HR], 0.27; 95% confidence interval [CI], 0.17–0.41; P BRCAm group (HR, 0.45; 95% CI, 0.34–0.61; P