An individualized starting dose (ISD) of niraparib maintenance therapy yielded a favorable overall survival (OS) trend compared to placebo among patients with platinum-sensitive recurrent ovarian cancer (PSROC). These findings from the final analysis of the randomized, double-blind, placebo-controlled phase 3 NORA trial will be presented at the 2024 Society of Gynecologic Oncology (SGO) annual meeting in San Diego, California.

Results of the NORA trial demonstrated that niraparib maintenance therapy using an ISD yielded a significant improvement in progression-free survival (PFS) during the primary analysis, as well as a favorable trend in OS during the interim analysis regardless of patients’ germline BRCA mutation (gBRCAm) status. There has previously been inconsistent OS trends shown among patients without gBRCAm in similar trials of poly (ADP-ribose) polymerase (PARP) inhibitors in the same setting.

A total of 265 patients with PSROC who had responded to their last platinum-based chemotherapy were enrolled in this trial and randomized on a 2-to-1 basis to receive either niraparib (n = 177) or placebo (n = 88) once daily. After a protocol amendment, an ISD was implemented, consisting of 200 mg for patients with a bodyweight <77 kg and/or platelet count <150x10³/μl, or 300 mg if they did not meet these criteria. The primary end point was OS with secondary and exploratory end points of chemotherapy-free interval (CFI) and time to treat subsequent anticancer therapy (TFST).

At the time of data cutoff, the median follow-up for OS was 57.9 months. Among patients who received placebo, subsequent PARP inhibitor therapy was administered to 46.6% of patients (n = 41). A total of 138 (52.1%) OS events were reported. In the overall population, the niraparib group had a median OS of 51.5 months vs 47.6 months in the placebo group (hazard ratio [HR], 0.86). Patients with and without gBRCAm exhibited a consistent OS trend.

The median CFI of the overall population was 19.7 months in the niraparib group vs 10.1 months in the placebo group (HR, 0.47). The median TFST was 16.6 months in the niraparib group vs 7.7 months in the placebo group (HR, 0.39). The median time to progression on second-line therapy (PFS-2) was 27.5 months in the niraparib group vs 17.3 months in the placebo arm (HR, 0.52). No new safety signals were observed.  There were 3 patients in the niraparib group who experienced myelodysplastic syndromes/acute myeloid leukemia.

Wu et al concluded, “Niraparib maintenance therapy using ISD demonstrated a favorable OS trend versus placebo among patients with PSROC, regardless of gBRCAm status, which continues to support the use of niraparib maintenance therapy in the all-comer population of PSROC.”

Source:

Wu X, Zhu J, Yin R, et al. Niraparib maintenance therapy using an individualized starting dose in patients with platinum-sensitive, recurrent ovarian cancer (NORA Trial): Final overall survival analysis of a randomized, double-blind, placebo-controlled, phase III trial. Presented at the SGO Annual Meeting & Exposition; March 16-18, 2024; San Diego, California.