Medline ® Abstract for Reference 51
Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer.
Mirza MR, Monk BJ, Herrstedt J, Oza AM, Mahner S, Redondo A, Fabbro M, Ledermann JA, Lorusso D, Vergote I, Ben-Baruch NE, Marth C, Mądry R, Christensen RD, Berek JS, Dørum A, Tinker AV, du Bois A, González-Martín A, Follana P, Benigno B, Rosenberg P, Gilbert L, Rimel BJ, Buscema J, Balser JP, Agarwal S, Matulonis UA, ENGOT-OV16/NOVA Investigators
N Engl J Med. 2016;375(22):2154. Epub 2016 Oct 7.
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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; P<0.001 for all three comparisons). The most common grade 3 or 4 adverse events that were reported in the niraparib group were thrombocytopenia (in 33.8%), anemia (in 25.3%), and neutropenia (in 19.6%), which were managed with dose modifications.
CONCLUSIONS: Among patients with platinum-sensitive, recurrent ovarian cancer, the median duration of progression-free survival was significantly longer amongthose receiving niraparib than among those receiving placebo, regardless of the presence or absence of gBRCA mutations or HRD status, with moderate bone marrow toxicity. (Funded by Tesaro; ClinicalTrials.gov number, NCT01847274 .).
From the Nordic Society of Gynecological Oncology and Rigshospitalet-Copenhagen University Hospital, Copenhagen (M.R.M.), Odense University Hospital (J.H.) and European Network for Gynacological Oncological Trial and Research Unit of General Practice, Institute of Public Health, University of Southern Denmark, Odense (R.D.C.) - all in Denmark; University of Arizona and Creighton University-Phoenix, Phoenix (B.J.M.), and Arizona Oncology Associates, Tuscon (B.J.M., J.B.) - all in Arizona; Princess Margaret Consortium, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto (A.M.O.), British Columbia Cancer Agency, Vancouver (A.V.T.), and McGill University-McGill University Health Centre, Montreal (L.G.) - all in Canada; Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) and the University of Munich, Munich (S.M.), and Kliniken Essen Mitte, Essen (A.B.) - both in Germany; Grupo Español de Investigación en Cáncer de Ovario (GEICO) and Hospital Universita