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

Objective The PRIMA/ENGOT-OV26/GOG-3012 study (NCT02655016) was amended to prospectively evaluate the safety/efficacy of an individualized starting dose (ISD) of niraparib compared to the approved fixed starting dose (FSD) regimen.

Materials and methods This double-blind, placebo-controlled, phase 3 study randomized 733 patients with newly-diagnosed advanced OC who responded to first-line platinum-based chemotherapy. The protocol was amended from a 300-mg FSD for all patients to an ISD regimen: 200 mg QD in patients with bodyweight < 77 kg and/or platelet count < 150,000/µL or 300 mg QD in all others. Exposure, efficacy, and safety data were compared between the regimens.

Results Patients who received a FSD (0.59; 95% CI, 0.46-0.76) or ISD (0.69; 95% CI, 0.48-0.98) showed similar improvements in progression-free survival compared to placebo. 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 were similar between the subgroups. The safety profile among patients in the niraparib arm (n=484), including grade ≥3 hematologic toxicities, improved with the incorporation of the ISD regimen (Table)

Grade ≥3 hematologic toxicities in patients who received a fixed starting dose (FSD) vs an individualized starting dose (ISD)

Grade ≥3 hematologic toxicities, n (%)	FSD Niraparib n = 315	ISD Niraparib n = 169	FSD Placebo n = 158	ISD Placebo n = 86
Thrombocytopenia event	152 (48)	36 (21)	0	1 (1)
Anemia event	112 (36)	38 (22)	3 (2)	1 (1)
Neutropenia event	75 (24)	25 (15)	2 (1)	1 (1)

Summary ISD in the first-line maintenance setting provided comparable efficacy to FSD while reducing the risk of hematologic toxicities.

Sponsor GlaxoSmithKline, Waltham, MA, USA

Interessenkonflikt

Frederik Marmé reports advisory board fees from Tesaro outside the submitted work. M. Mirza reports ownership interests and leadership fees from Karyopharm Therapeutics and Sera Prognostics; personal fees from Roche, Genmab, BioCad, Sotio, Geneos Therapeutics, Merck, Oncology Venture, Seattle Genetics, Sera Prognostics, Takeda Pharmaceutical Company Ltd, and Zailab; grants and personal fees from AstraZeneca, Clovis Oncology, Pfizer, Tesaro; and grants from Boehringer Ingelheim outside of the submitted work. A. González-Martín reports personal fees and non-financial support from AstraZeneca; grants, personal fees and non-financial support from TESARO: A GSK Company and Roche Holding AG; personal fees from Clovis Oncology, Merck & Co. Inc., Genmab, INMUNOGEN, Pharma Mar, and Oncoinvent AS outside the submitted work. W. Graybill reports personal fees from TESARO outside the submitted work. D. O’Malley reports consultancy/advisory board fees from Tesaro, Immunogen, Eisai, Agenus, GSK, Genentech/Roche, Merck; advisory board/steering committee and consultancy fees from Clovis; consultancy fees from Ambry and Abbvie; advisory board fees from Janssen/J&J, Regeneron, Novacure, Myraid Genetics and Tarveda; steering committee fees for Amgen; and institutional funding for clinical trials from VentiRx, Array Biopharma, EMD Serono, Ergomed, Ajinomoto Inc, Ludwig Cancer Research, Stemcentrx, Inc, CERULEAN PHARMA, GOG Foundation, BMS, Serono Inc, TRACON Pharmaceuticals, Yale Univ, New Mexico Cancer Care Alliance, INC Research, Inc., Inventiv Health Clinical, Iovance Biotherapeutics Inc, and PRA Intl outside the submitted work. L. Gaba has nothing to disclose. O. W. S. Yap has nothing to disclose. E. Guerra reports Consulting fees, advisory board fees, and travel support from Roche; consulting fees and advisory board fees from Clovis Oncology, Tesaro, PharmaMar, AstraZeneca, Merck Sharp & Dohme, and GlaxoSmithKline; and travel support from Baxter and GlaxoSmithKline/Tesaro outside the submitted work. P. Rose has nothing to disclose. J. F. Baurain has nothing to disclose. S. Ghamande reports consulting fees from Seattle Genetics; speakers bureau from Tesaro/GSK; and research funding from GSK, Merck. Roche, Genentech, Takeda, Seattle Genetics, Advaxis, BMS, Clovis, Abbvie, and Tesaro outside the submitted work. H. Denys reports consulting or advisory roles at Pfizer, Roche, PharmaMar, AstraZeneca, Eli Lilly, Novartis, Amgen, Tesaro; institutional research funding from Roche; and travel and accommodations support from Pfizer, Roche, PharmaMar, and Teva outside the submitted work. E. Prendergast reports a consulting or advisory role at AstraZeneca and Merck outside the submitted work. C. Pisano has nothing to disclose. P. Follana has nothing to disclose. K. Baumann has nothing to disclose. P. M. Calvert has nothing to disclose. J. Korach has nothing to disclose. Y. Li is an employee of GlaxoSmithKline D. Gupta is an employee of GlaxoSmithKline B. Monk reports grants and personal fees from Tesaro outside of the submitted work.

Publication History

Article published online:
07 October 2020