Tolerability of the niraparib individualized starting dose in the PRIMA/ENGOT-OV26/GOG-3012 trial of niraparib first-line maintenance therapy
- PMID: 39013265
- DOI: 10.1016/j.ejca.2024.114157
Tolerability of the niraparib individualized starting dose in the PRIMA/ENGOT-OV26/GOG-3012 trial of niraparib first-line maintenance therapy
Abstract
Purpose: To explore safety and tolerability parameters for the niraparib individualized starting dose (ISD) in patients with newly diagnosed advanced ovarian cancer that responded to platinum-based chemotherapy who participated in the phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial (NCT02655016).
Methods: The PRIMA protocol was amended so newly enrolled patients received an ISD based on baseline body weight/platelet count. In this ad hoc analysis, the timing, duration, and resolution of the first occurrence of common any-grade hematologic (thrombocytopenia, anemia, neutropenia) and nonhematologic (nausea, asthenia/fatigue, constipation, insomnia, hypertension) treatment-emergent adverse events (TEAEs) were evaluated by treatment arm in the ISD safety population (data cutoff, November 17, 2021; median follow-up, 3.5 years).
Results: Of 733 randomized patients, 255 were enrolled after the ISD protocol amendment and received ≥ 1 dose of study treatment (niraparib, 169; placebo, 86). In the niraparib arm, median times to first events were 22.0-35.0 days for hematologic TEAEs and 7.0-56.0 days for nonhematologic TEAEs. First events resolved in ≥ 89.8% of patients for hematologic TEAEs; for nonhematologic TEAEs, resolution rates ranged from 55.3% (insomnia) to 86.0% (nausea). Median durations of first hematologic TEAEs were ≤ 16.0 days, but for first nonhematologic TEAEs ranged from 18.0 days (nausea) to 134.0 days (insomnia).
Conclusion: The niraparib ISD was generally well tolerated and TEAEs were manageable. Common hematologic and nonhematologic TEAEs occurred early and first events of hematologic TEAEs had a short duration (≈ 2 weeks) and a high resolution rate. These findings support close monitoring immediately following niraparib initiation and may help inform patient expectations for niraparib safety.
Keywords: Maintenance therapy; Niraparib; Ovarian cancer; PARP inhibitor; Tolerability.
Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.
Conflict of interest statement
Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Vulsteke reports medical writing support from GSK; consulting fees from Astellas, Atheneum Partners, Bristol Myers Squibb, GSK, Janssen-Cilag, Leo Pharma, Merck Sharp & Dohme, and Roche; advisory board fees from AstraZeneca, Bayer, GSK, Janssen-Cilag, Leo Pharma, Merck Sharp & Dohme; and travel support from Pfizer and Roche. Dr Chambers has nothing to disclose. Dr Rubio Pérez has nothing to disclose. Dr Chan reports research, consulting, and speakers' bureau fees from AbbVie, Acerta, Aravive, AstraZeneca, Clovis, Eisai, GSK, Merck, and Roche. Dr Raaschou-Jensen reports advisory board fees from Eisai. Dr Zhuo has nothing to disclose. Dr Lorusso reports consulting fees from Amgen, AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, MSD, PharmaMar, and Seagen; honoraria from AstraZeneca, Clovis Oncology, GSK, MSD, and PharmaMar; payment for expert testimony from Clovis Oncology; support for attending meetings and/or travel from AstraZeneca, Clovis Oncology, GSK, PharmaMar, and Roche; personal advisory board fees from AstraZeneca, Clovis Oncology, Corcept, Genmab, GSK, Immunogen, Merck Serono, MSD, Oncoinvent, PharmaMar, Seagen, and Sutro; member of board of directors at GCIG (no compensation); medical writing support from Clovis Oncology, GSK, MSD, and PharmaMar; and institutional funding for work in clinical trials from AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, Incyte, MSD, Novartis, PharmaMar, Roche, and Seagen. Dr Herzog reports personal consulting fees from Aadi, AstraZeneca, Caris, Clovis, Eisai, Epsilogen, Genentech, GSK, Immunogen, J&J, Merck, Mersana, and Seagen; participation on a data safety monitoring board or advisory board from Corcept; and leadership role on the GOG Foundation Board and president of GOG Partners. Dr de la Motte Rouge reports consulting fees from AstraZeneca, Clovis Oncology, Eisai, Gilead, GSK, MSD, Novartis, Pfizer, and Sanofi; honoraria from AstraZeneca, GSK, MSD, NetCancer, and Pfizer; and travel support from Gilead, MSD, and Pfizer. Dr Thomes Pepin has nothing to disclose. Dr Braicu reports honoraria from AstraZeneca, GSK, and Merck; consulting or advisory roles at AstraZeneca and GSK; institutional research funding from AstraZeneca, Bayer, Clovis, Eisai, GSK, Merck, and Resolve; travel support from AstraZeneca; and relationship with medical director of the North Eastern German Society of Gynecological Oncology (NOGGO). Dr Chen reports author royalties from UpToDate and serves on the board of directors of the American College of Obstetricians and Gynecologists, on the board of governors of the American College of Surgeons, and as a board member for the NCI PDQ Cancer Genetics Board. Dr Levy has nothing to disclose. Dr Barter has nothing to disclose. Dr Barretina-Ginesta reports consulting or advisory role fees from AstraZeneca, Clovis Oncology, GSK, MSD, PharmaMar, and Roche; and travel support from AstraZeneca, GSK, MSD, PharmaMar, and Roche. Dr Joosens reports travel fees from MSD. Ms York and Dr Malinowska are current employees of GSK. Dr González-Martín reports fees for different educational or advisory-related activities from Alkermes, Amgen, AstraZeneca, Clovis, Genmab, GSK, Hedera Dx, Immunogen, Illumina, Karyopharm, Mersana, MSD, Novartis, Novocure, Oncoinvent, PharmaMar, Regeneron, Roche, Seagen, Sotio, Sutro, Takeda, and Tubulis. Dr Monk reports consulting fees from Agenus, Akeso Biopharma, Amgen, Aravive, Bayer, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, ImmunoGen, Iovance, Karyopharm, MacroGenics, Mersana, Myriad, Novartis, Novocure, Pfizer, Puma, Regeneron, Sorrento, US Oncology Research, and VBL and speakers’ bureau honoraria from AstraZeneca, Clovis, Eisai, Merck, Roche/Genentech, and Tesaro/GSK.
Publication types
MeSH terms
Substances
Associated data
LinkOut - more resources
Full Text Sources
Medical
