Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer
Top Cited Papers
- 1 December 2016
- journal article
- research article
- Published by Massachusetts Medical Society in The New England Journal of Medicine
- Vol. 375 (22), 2154-2164
- https://doi.org/10.1056/nejmoa1611310
Abstract
Niraparib is an oral poly(adenosine diphosphate [ADP]–ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer. We sought to evaluate the efficacy of niraparib versus placebo as maintenance treatment for patients with platinum-sensitive, recurrent ovarian cancer. In this randomized, double-blind, phase 3 trial, patients were categorized according to the presence or absence of a germline BRCA mutation (gBRCA cohort and non-gBRCA cohort) and the type of non-gBRCA mutation and were randomly assigned in a 2:1 ratio to receive niraparib (300 mg) or placebo once daily. The primary end point was progression-free survival. Of 553 enrolled patients, 203 were in the gBRCA cohort (with 138 assigned to niraparib and 65 to placebo), and 350 patients were in the non-gBRCA cohort (with 234 assigned to niraparib and 116 to placebo). Patients in the niraparib group had a significantly longer median duration of progression-free survival than did those in the placebo group, including 21.0 vs. 5.5 months in the gBRCA cohort (hazard ratio, 0.27; 95% confidence interval [CI], 0.17 to 0.41), as compared with 12.9 months vs. 3.8 months in the non-gBRCA cohort for patients who had tumors with homologous recombination deficiency (HRD) (hazard ratio, 0.38; 95% CI, 0.24 to 0.59) and 9.3 months vs. 3.9 months in the overall non-gBRCA cohort (hazard ratio, 0.45; 95% CI, 0.34 to 0.61; PBRCA mutations or HRD status, with moderate bone marrow toxicity. (Funded by Tesaro; ClinicalTrials.gov number, NCT01847274.)Keywords
This publication has 11 references indexed in Scilit:
- Homologous Recombination Deficiency (HRD) Score Predicts Response to Platinum-Containing Neoadjuvant Chemotherapy in Patients with Triple-Negative Breast CancerClinical Cancer Research, 2016
- European Network of Gynaecological Oncological Trial Groups’ Requirements for Trials Between Academic Groups and Industry Partners—First Update 2015International Journal of Gynecologic Cancer, 2015
- The poly(ADP-ribose) polymerase inhibitor niraparib (MK4827) in BRCA mutation carriers and patients with sporadic cancer: a phase 1 dose-escalation trialThe Lancet Oncology, 2013
- The impact of second to sixth line therapy on survival of relapsed ovarian cancer after primary taxane/platinum-based therapyAnnals of Oncology, 2012
- Olaparib Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian CancerThe New England Journal of Medicine, 2012
- A Phase I Study of Veliparib in Combination with Metronomic Cyclophosphamide in Adults with Refractory Solid Tumors and LymphomasClinical Cancer Research, 2012
- Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised studyThe Lancet Oncology, 2011
- Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trialThe Lancet, 2010
- Discovery of 2-{4-[(3S)-Piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): A Novel Oral Poly(ADP-ribose)polymerase (PARP) Inhibitor Efficacious in BRCA-1 and -2 Mutant TumorsJournal of Medicinal Chemistry, 2009
- Inhibition of Poly(ADP-Ribose) Polymerase in Tumors fromBRCAMutation CarriersThe New England Journal of Medicine, 2009