Evaluation of an individualized starting-dose of niraparib in the PRIMA/ENGOT-OV26/GOG-3012 study.

Abstract

6050 Background: Niraparib is approved at a fixed starting dose (FSD) of 300 mg QD for maintenance treatment of patients (pts) with recurrent ovarian cancer (OC) achieving a complete or partial response to platinum-based chemotherapy based in the ENGOT-OV16/NOVA study. A post-hoc analysis of NOVA showed baseline bodyweight (BW) and platelet count (PC) were predictive for hematologic toxicities and dose reductions. Following this analysis, the PRIMA/ENGOT-OV26/GOG-3012 study was amended to prospectively evaluate the safety and efficacy of an individualized starting dose (ISD) regimen. Methods: This double-blind, placebo-controlled, phase III study randomized 733 pts with newly diagnosed advanced OC with a complete or partial response to first-line (1L) platinum-based chemotherapy. The protocol was amended to change the dose from 300 mg FSD for all patients to an ISD regimen: 200 mg QD in pts with BW <77 kg and/or PC <150,000/µL or 300 mg QD in pts with BW ≥77 kg and PC ≥150,000/µL. Exposure, efficacy, and safety data were compared between patients treated with FSD vs ISD. Results: Efficacy in the ISD subgroup was comparable to the FSD subgroup relative to placebo (Table). An interaction test showed no treatment difference between ISD and FSD at the pre-specified 0.10 significance level ( p=0.30). Medians for dose intensity and relative dose intensity in pts who received niraparib were similar. The overall safety profile among pts in the niraparib arm (n=484), including grade ≥3 hematologic toxicities, improved with the ISD. Conclusions: The ISD in the 1L maintenance setting provides comparable efficacy to the FSD while reducing the risk of hematologic toxicities. No new safety signals were identified. Clinical trial information: NCT02655016. [Table: see text]