Dr Elias on Outcomes With Niraparib Maintenance Therapy in Ovarian Cancer

“The primary outcome was progression-free survival. For women randomized to niraparib, the chances of progression or death were reduced by 70%. It was a very positive study."

Kevin Elias, MD, the Lillian and Seth Harris Endowed Chair for Ovarian Cancer Research at the Cleveland Clinic, discussed key efficacy findings from the phase 3 PRIMA (NCT02655016) and NOVA (NCT01847274) trials, both of which evaluated the PARP inhibitor niraparib (Zejula) as maintenance therapy in patients with ovarian cancer.

Although these studies shared the same investigational agent, they differed in design, patient population, and disease setting, Elias noted. The PRIMA trial enrolled patients with newly diagnosed, high-grade serous or endometrioid ovarian cancer who achieved either a complete or partial response following first-line platinum-based chemotherapy, regardless of BRCA mutation or homologous recombination deficiency (HRD) status. Patients were randomized to receive niraparib 300 mg once daily or placebo, with progression-free survival (PFS) as the primary end point.

At the 5-year follow-up, long-term efficacy outcomes continued to favor niraparib maintenance therapy over placebo in patients with ovarian cancer. The 5-year PFS rate was 22% in the overall population compared with 12% in the placebo arm. This benefit was more pronounced among patients with HRD-positive disease, in which 35% of those treated with niraparib remained progression free at 5 years vs 16% with placebo. The safety profile for maintenance niraparib remained consistent with prior analyses, with no new safety signals observed over long-term follow-up. The incidence of myelodysplastic syndrome and acute myeloid leukemia was less than 2.5% overall, occurring in 2.3% of patients receiving niraparib and 1.6% of those on placebo.

In contrast, the NOVA trial examined niraparib in the recurrent disease setting, enrolling patients with platinum-sensitive recurrent ovarian cancer who had achieved a response to their most recent platinum-based regimen. Patients were randomly assigneda to receive niraparib at 300 mg daily or placebo. Patients were stratified by germline BRCA mutation status. As in PRIMA, PFS served as the primary end point. Elias emphasized that patients who received niraparib experienced a significantly longer PFS compared with those who received placebo across all analyzed subgroups. In the germline BRCA-mutated cohort, the median PFS was 21.0 months with niraparib vs 5.5 months with placebo (HR, 0.27; 95% CI, 0.17-0.41). Among patients without BRCA mutations but whose with HRD-positive tumors, the median PFS was 12.9 months with niraparib vs 3.8 months with placebo (HR, 0.38; 95% CI, 0.24-0.59). In the overall non-BRCA-mutated cohort, which included both HRD-positive and HRD-negative patients, the median PFS was 9.3 months with niraparib compared with 3.9 months with placebo (HR, 0.45; 95% CI, 0.34-0.61; P < .001 for all comparisons). These results demonstrate a consistent and statistically significant PFS advantage with niraparib maintenance therapy across genomic subgroups, including patients without germline BRCA mutations.

Taken together, PRIMA and NOVA established niraparib as an effective maintenance option across multiple disease settings in ovarian cancer, Elias underscored. Although the benefit is most pronounced in BRCA-mutated and HRD-positive populations, the observed efficacy in HRD-negative subgroups supports a more inclusive therapeutic role for PARP inhibition, he concluded.