Long-Term Safety and Secondary Efficacy End Points in the ENGOT-OV16/NOVA Phase 3 Trial of Niraparib in Recurrent Ovarian Cancer

Final analysis of the NOVA trial supports the long-term progression-free survival benefit and safe use of niraparib beyond first progression for maintenance treatment in patients with platinum-sensitive recurrent ovarian cancer.

The randomized, double-blind, placebo-controlled, phase 3 NOVA (ENGOT-OV16) study demonstrated that maintenance therapy with niraparib significantly prolongs progression-free survival (PFS) in patients with platinum-sensitive recurrent ovarian cancer, regardless of germline BRCA mutation (gBRCAm) or homologous recombination deficiency biomarker status. Long-term safety and data on secondary efficacy outcomes of the NOVA trial were reported at the 2021 Society of Gynecologic Oncology Annual Meeting.

The NOVA trial enrolled patients with platinum-sensitive recurrent ovarian cancer. Eligible patients were enrolled into 1 of 2 cohorts by gBRCAm status (gBRCAm or non-gBRCAm). Stratification was by PFS after the penultimate platinum therapy (6 to <12 months vs ≥12 months), best response to the last platinum-based therapy (complete or partial), and previous bevacizumab (yes/no). Eligible patients were randomized (2:1) to receive niraparib (300 mg every day) or placebo. The primary end point was PFS as assessed by blinded independent central review; exploratory secondary end points were second PFS and overall survival (OS). The data cutoff date was October 2020. At data cutoff, 127 deaths occurred in the gBRCAm cohort, and 238 deaths occurred in the non-gBRCAm cohort.

Long-term safety analysis showed that hematologic treatment-emergent adverse effects decreased after the first year. From year 1 to years 2-3, respectively, the incidence of grade ≥3 thrombocytopenia decreased from 33.8% to 2.8%, anemia decreased from 25.6% to 0.7%, and neutropenia decreased from 19.3% to 2.1%. Secondary malignancies of myelodysplastic syndromes or acute myeloid leukemia occurred in 13 (3.5%) patients receiving niraparib (gBRCAm, n = 9; non-gBRCAm, n = 4) compared with 3 such malignancies (1.7%) in patients receiving placebo.

A total of 553 patients were randomized in the NOVA study. At a median follow-up of 66 months, prolongation of the second PFS was noted in both the gBRCAm cohort (hazard ratio [HR], 0.67) and non-gBRCAm cohort (HR, 0.81).

Restricted mean survival time analyses for OS up to 72 months in the niraparib and placebo arms were as follows: 45.9 months with niraparib in the gBRCAm cohort (vs 43.2 months with placebo; difference of 2.7 months); and 38.5 months with niraparib in the non-gBRCAm cohort (vs 39.1 months with placebo; difference of –0.6 months). However, it is notable that the NOVA study was not powered for OS, and interpretation of OS analysis was confounded by a high rate of crossover and missing data. A total of 46% (30/65) in the gBRCAm cohort and 13% (15/116) in the non-gBRCAm cohort of the placebo arm went on to receive subsequent poly (ADP-ribose) polymerase–inhibitor therapy (crossover) after disease progression. Survival status data were not obtained for approximately 15% of patients, and postprogression therapy data were not available for 25% of patients.

Final analysis of the NOVA trial supports the long-term safe use of niraparib maintenance treatment and PFS benefit beyond first progression in patients with platinum-sensitive recurrent ovarian cancer.

Source: Matulonis U, Herrstedt J, Oza A, et al. Long-term safety and secondary efficacy endpoints in the ENGOT-OV16/NOVA phase III trial of niraparib in recurrent ovarian cancer. Gynecol Oncol. 2021;162(suppl_1):S24-S25.