OVARIO phase II trial of combination niraparib plus bevacizumab maintenance therapy in advanced ovarian cancer following first-line platinum-based chemotherapy with bevacizumab

Abstract

Objective: To assess safety and efficacy of niraparib + bevacizumab as a first-line maintenance therapy for patients with newly diagnosed advanced ovarian cancer.

Methods: This multicenter, phase II, single-arm, open-label study enrolled adult patients with stage IIIB to IV ovarian, fallopian tube, or primary peritoneal cancer (NCT03326193). Patients were required to have an attempt at debulking surgery and have a complete response, partial response, or no evidence of disease following first-line, platinum-based chemotherapy with ≥3 cycles of bevacizumab. The primary endpoint was the progression-free survival (PFS) rate at 18 months. Secondary endpoints included PFS, overall survival, and safety.

Results: Among the 105 evaluable patients, the PFS rate at 18 months was 62% (95% CI 52-71%) in the overall population and 76% (95% CI 61-87) in the homologous recombination deficient (HRd), 47% (95% CI 31-64%) in the HR proficient (HRp), and 56% (95% CI 31-79%) in the HR not determined (HRnd) subgroups (December 24, 2020, cutoff). After a median follow-up time of 28.7 months (IQR, 23.9-32.5 months), median PFS was 19.6 months (95% CI 16.5-25.1) in the overall population (N = 105) and 28.3 months (95% CI 19.9-NE), 14.2 months (95% CI 8.6-16.8), and 12.1 months (95% CI 8.0-NE) in the HRd, HRp, and HRnd subgroups, respectively (June 16, 2021, cutoff). The most common any-grade treatment-related adverse events (related to niraparib and/or bevacizumab) were thrombocytopenia (74/105), fatigue (60/105), and anemia (55/105; December 24, 2020, cutoff).

Conclusion: Niraparib + bevacizumab first-line maintenance therapy displayed promising PFS results. Safety was consistent with the known safety profiles of niraparib and bevacizumab as monotherapy.

Keywords: Advanced; Bevacizumab; Niraparib; Ovarian cancer; PARP; VEGF.

Conflict of interest statement

Declaration of Competing Interest MMH reports honoraria from Clinical Care Operations and GlaxoSmithKline; and advisory board fees from AstraZeneca-Merck, Immunogen and GlaxoSmithKline. TCK reports consulting and speakers' bureau fees from GlaxoSmithKline. GSW reports she served as PI for a clinical trial for which the institute received payment for conducting the trial from Abbvie, Astellas, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Cascadian Therapeutics, Celgene, Celldex Therapeutics, Daiichi Sankyo Pharma, Dana Farber Cancer Institute, G1Therapeutics, Genentech, H3BioMedicine Inc., Hoffmann-LaRoche, ImmunoGen, Incyte, Innocrin Pharm, Jansen, Lilly, Macrogenics, Medivation, Merrimack, NanoString Technologies, Novartis, Nucana, Odonate Therapeutics, Pfizer, Seattle Genetics, Sermonix Pharm, Taiho Oncology, and Tesaro. EH reports institutional research grant from Tesaro/GSK, Abbvie, Acerta Pharma, ADC Therapeutics, AKESOBIO Australia, Amgen, Aravive, ArQule, Arvinas, AtlasMedX, Black Diamond, Boehringer Ingelheim, Clovis, Compugen, Curis, CytomX, Dana Farber Cancer Inst, Deciphera, eFFECTOR Therapeutics, Ellipses Pharma, EMD Serono, Fochon, FujiFilm, G1 Therapeutics, H3 Biomedicine, Harpoon, Hutchinson MediPharma, Immunogen, Immunomedics, Incyte, InvestisBio, Jacobio, Karyopharm, Leap Therapeutics, Lilly, Lycera, Mabspace Biosciences, Macrogenics, MedImmune, Merck, Mersana, Merus, Millenium, Molecular Templates, Myraid Genetic Labs, Novartis, Nucana, Olema, OncoMed, Onconova Therapeutics, ORIC Pharmaceuticals, Orinove, Pfizer, PharmaMar, Pieris Pharmaceuticals, Pionyr Immunotherapeutics, Plexxikon, Radius Health, Regeneron, Repertoire Immune Medicine, Rgenix, Roche/Genentech, SeaGen, Sermonix Pharmaceuticals, Shattuck Labs, Silverback, StemCentRx, Sutro, Syndax, Syros, Taiho, TapImmune, Treadwell Therapeutics, Verastem, Vincerx Pharma, Zenith Epigenetics, Zymeworks and institional consulting fees from Arcus, Arvinas, Black Diamond, Boehringer Ingelheim, CytomX, Dantari, Deciphera Pharmaceuticals, Eisai, H3 Biomedicine, iTeos, Janssen, Lilly, Loxo, Merck, Mersana, Novartis, Pfizer, Puma Biotechnology, Relay Therapeutics, Roche/Genentech, SeaGen, Silverback Therapeutics. ELF has nothing to disclose. JB is an employee of GlaxoSmithKline. EKK is a former employee of GlaxoSmithKline and reports stock and stock option ownership at the time of GSK employment. PW is an employee of GlaxoSmithKline. DG is an employee of GlaxoSmithKline. AC reports consulting fees from Tempus and advisory board fees from GlaxoSmithKline. HJG has nothing to disclose. GEK reports speaker bureau fees from AstraZeneca, Clovis, GlaxoSmithKline/Tesaro, and Myriad Genetics. RGM reports personal fees from Fujirebio Diagnostics Inc., and Humphries Pharmaceutical; and institutional grants from Angle Plc. DLR reports research contracts paid to her institution from Aravive, Arch Oncology, Celsion, Clovis, Deciphera, Fujifilm, GlaxoSmithKline, Harpoon, Karyopharm, Mersana, Plexxikon, Roche, Shattuck Labs, Syros, and Tesaro; honoraria fees from GOG Foundation; travel support from Tesaro; advisory board fees from AstraZeneca, Bayer, Deciphera, Foundation Medicine, Genentech, Mersana, and Tesaro/GlaxoSmithKline; and unpaid leadership as the vice chair of board of directors for National Ovarian Cancer Coalition.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.