Abstract
Introduction/BackgroundThe PRIMA/ENGOT-OV26/GOG-3012 trial showed that niraparib significantly improves progression-free survival (PFS) in patients with newly diagnosed advanced ovarian cancer (aOC) that responded to front-line platinum-based chemotherapy (hazard ratio, 0.62; 95% CI, 0.50–0.76). Based on these results, niraparib has been approved in the United States and the European Union for front-line maintenance treatment in patients with aOC. In this post hoc analysis, we report the efficacy of niraparib in patients with BRCA-mutated (BRCAm) aOC with an emphasis on efficacy and safety of fixed vs. individualized starting doses (FSD vs. ISD).MethodologyIn this double-blind, placebo-controlled, randomised phase 3 trial, patients with newly diagnosed, high-grade aOC who responded to platinum-based chemotherapy were randomised 2:1 to receive FSD of niraparib 300 mg orally once daily (QD) or placebo. The trial was amended to incorporate an ISD of 200 mg orally QD for patients with a body weight <77 kg or platelet count <150,000/μL, and 300 mg QD in patients with a body weight ≥77 kg and platelet count ≥150,000/μL. Patients were stratified by best response to first-line chemotherapy (complete/partial response), receipt of neoadjuvant chemotherapy (yes/no), and homologous recombination status (deficient/proficient and not determined). BRCA status was determined in tumour samples at screening via the myChoice test (Myriad®). The post hoc BRCAm subgroup PFS analysis was performed using a stratified Cox proportional hazards model and Kaplan-Meier methodology. Safety and patient-reported outcome analyses were also performed.ResultsThe intention-to-treat population comprised 733 randomised patients, of which 223 (30%) had BRCAm tumours. Of those, 144 (65%) received FSD and 79 (35%) received ISD. Niraparib provided a comparable PFS benefit over placebo in patients receiving both FSD (hazard ratio, 0.44; 95% CI 0.26–0.73) and ISD (hazard ratio 0.29; 95% CI 0.13–0.67). A PFS subgroup analysis by patient characteristics is shown in table 1. A summary of grade ≥3 selected adverse events is shown in table 2. Abstract 571 Table 1PFS subgroup analysis analysis in patient with BRACAmAbstract 571 Table 2Summary of grade ≥3 adverse events in patients with BRCAm aOCConclusionNiraparib significantly improved PFS when utilised as maintenance treatment after front-line therapy in patients with BRCAm aOC. Patients receiving FSD or ISD derived similar PFS benefit, while the ISD group showed an improved safety profile.Disclosures Dr. Graybill reports personal fees from GlaxoSmithKline. Dr. Redondo reports institutional research funding from PharmaMar, Roche, and Eisai; and advisory roles at PharmaMar, AstraZeneca, Tesaro, Roche, and Eisai. Dr. O’Malley reports personal fees from Immunogen, Eisai, Agenus, GlaxoSmithKline: Consultant/Advisory Board for Clovis, Ambry, Abbvie, Janssen/J&J, Regeneron, Novacure, Myraid Genetics, Tarveda, Amgen, VentiRx, Array Biopharma, EMD Serono, Ergomed; Steering committee for Genentech/Roche and Merck; Institutional funding from Ajinomoto Inc, Ludwig Cancer Research, Stemcentrx, Inc, CERULEAN PHARMA, GOG Foundation, BMS, Serono Inc, TRACON Pharmaceuticals, Yale University, New Mexico Cancer Care Alliance, INC Research, Inc., Inventiv Health Clinical, Iovance Biotherapeutics, Inc, and PRA International. Dr. Gupta is an employee of GlaxoSmithKline. Dr. González-Martín reports personal fees and non-financial support from AstraZeneca; grant and personal fees from GlaxoSmithKline, Clovis Oncology, Roche Holding AG, Merck & Co., Inc., Genmab, INMUNOGEN, Pharma Mar, S.A., and Oncoinvent AS. Dr. Monk reports consulting and advisory role at Merck, GlaxoSmithKline, Roche/Genentech, AstraZeneca, Advaxiz, Cerulean Pharma, Amgen, Immunogen, NuCana BioMed, Clovis Oncology, Pfizer, Mateon Therapeutics, Precision Oncology, Perthera, Abbvie, Myriad Pharmaceuticals, Incyte, VBL Therapeutics, Takeda, Samumed, Oncomed, OncoSec, ChemoID, Geistlich Pharma, Eisai and Chemocare; Speakers’ bureau at Roche/Genentech, AstraZeneca, Janssen, Clovis Oncology and GlaxoSmithKline; Honoraria from Merck, GlaxoSmithKline, Roche/Genentech, AstraZeneca, Advaxis, Immunogen, NuCana BioMed, Clovis Oncology, Pfizer, Mateon Therapeutics, Precision Oncology, Pethera, Abbvie, Myriad Pharmaceuticals, Incyte, Janssen, Amgen, Genmab, Samumed, Takeda, VBL Therapeutics, Puma Biotechnology, Immunomedics, Conjupro Biotherapeutics, Agenus, OncoQuest, ChemoID, Geistlich Pharma, Eisai and Chemocare; and Research funding from Novartis, Amgen, Genentech, Lilly, Janssen, Array BioPharma, GlaxoSmithKline, Morphotek, Pfizer, Advaxis, AstraZeneca, Immunogen, Regeneron, and Nucana. Drs. Korach, Han, Cloven and Knudsen have nothing to disclose.FundingGlaxoSmithKline (Waltham, MA)