TY - JOUR
T1 - Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer
AU - González-Martín, Antonio
AU - Pothuri, Bhavana
AU - Vergote, Ignace
AU - DePont Christensen, René
AU - Graybill, Whitney
AU - Mirza, Mansoor R
AU - McCormick, Colleen
AU - Lorusso, Domenica
AU - Hoskins, Paul
AU - Freyer, Gilles
AU - Baumann, Klaus
AU - Jardon, Kris
AU - Redondo, Andrés
AU - Moore, Richard G
AU - Vulsteke, Christof
AU - O'Cearbhaill, Roisin E
AU - Lund, Bente
AU - Backes, Floor
AU - Barretina-Ginesta, Pilar
AU - Haggerty, Ashley F
AU - Rubio-Pérez, Maria J
AU - Shahin, Mark S
AU - Mangili, Giorgia
AU - Bradley, William H
AU - Bruchim, Ilan
AU - Sun, Kaiming
AU - Malinowska, Izabela A
AU - Li, Yong
AU - Gupta, Divya
AU - Monk, Bradley J
AU - PRIMA/ENGOT-OV26/GOG-3012 Investigators
N1 - Copyright © 2019 Massachusetts Medical Society.
PY - 2019/12/19
Y1 - 2019/12/19
N2 - BACKGROUND: Niraparib, an inhibitor of poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP), has been associated with significantly increased progression-free survival among patients with recurrent ovarian cancer after platinum-based chemotherapy, regardless of the presence or absence of BRCA mutations. The efficacy of niraparib in patients with newly diagnosed advanced ovarian cancer after a response to first-line platinum-based chemotherapy is unknown.METHODS: In this randomized, double-blind, phase 3 trial, we randomly assigned patients with newly diagnosed advanced ovarian cancer in a 2:1 ratio to receive niraparib or placebo once daily after a response to platinum-based chemotherapy. The primary end point was progression-free survival in patients who had tumors with homologous-recombination deficiency and in those in the overall population, as determined on hierarchical testing. A prespecified interim analysis for overall survival was conducted at the time of the primary analysis of progression-free survival.RESULTS: Of the 733 patients who underwent randomization, 373 (50.9%) had tumors with homologous-recombination deficiency. Among the patients in this category, the median progression-free survival was significantly longer in the niraparib group than in the placebo group (21.9 months vs. 10.4 months; hazard ratio for disease progression or death, 0.43; 95% confidence interval [CI], 0.31 to 0.59; P<0.001). In the overall population, the corresponding progression-free survival was 13.8 months and 8.2 months (hazard ratio, 0.62; 95% CI, 0.50 to 0.76; P<0.001). At the 24-month interim analysis, the rate of overall survival was 84% in the niraparib group and 77% in the placebo group (hazard ratio, 0.70; 95% CI, 0.44 to 1.11). The most common adverse events of grade 3 or higher were anemia (in 31.0% of the patients), thrombocytopenia (in 28.7%), and neutropenia (in 12.8%). No treatment-related deaths occurred.CONCLUSIONS: Among patients with newly diagnosed advanced ovarian cancer who had a response to platinum-based chemotherapy, those who received niraparib had significantly longer progression-free survival than those who received placebo, regardless of the presence or absence of homologous-recombination deficiency. (Funded by GlaxoSmithKline; PRIMA/ENGOT-OV26/GOG-3012 ClinicalTrials.gov number, NCT02655016.).
AB - BACKGROUND: Niraparib, an inhibitor of poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP), has been associated with significantly increased progression-free survival among patients with recurrent ovarian cancer after platinum-based chemotherapy, regardless of the presence or absence of BRCA mutations. The efficacy of niraparib in patients with newly diagnosed advanced ovarian cancer after a response to first-line platinum-based chemotherapy is unknown.METHODS: In this randomized, double-blind, phase 3 trial, we randomly assigned patients with newly diagnosed advanced ovarian cancer in a 2:1 ratio to receive niraparib or placebo once daily after a response to platinum-based chemotherapy. The primary end point was progression-free survival in patients who had tumors with homologous-recombination deficiency and in those in the overall population, as determined on hierarchical testing. A prespecified interim analysis for overall survival was conducted at the time of the primary analysis of progression-free survival.RESULTS: Of the 733 patients who underwent randomization, 373 (50.9%) had tumors with homologous-recombination deficiency. Among the patients in this category, the median progression-free survival was significantly longer in the niraparib group than in the placebo group (21.9 months vs. 10.4 months; hazard ratio for disease progression or death, 0.43; 95% confidence interval [CI], 0.31 to 0.59; P<0.001). In the overall population, the corresponding progression-free survival was 13.8 months and 8.2 months (hazard ratio, 0.62; 95% CI, 0.50 to 0.76; P<0.001). At the 24-month interim analysis, the rate of overall survival was 84% in the niraparib group and 77% in the placebo group (hazard ratio, 0.70; 95% CI, 0.44 to 1.11). The most common adverse events of grade 3 or higher were anemia (in 31.0% of the patients), thrombocytopenia (in 28.7%), and neutropenia (in 12.8%). No treatment-related deaths occurred.CONCLUSIONS: Among patients with newly diagnosed advanced ovarian cancer who had a response to platinum-based chemotherapy, those who received niraparib had significantly longer progression-free survival than those who received placebo, regardless of the presence or absence of homologous-recombination deficiency. (Funded by GlaxoSmithKline; PRIMA/ENGOT-OV26/GOG-3012 ClinicalTrials.gov number, NCT02655016.).
KW - Administration, Oral
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Antineoplastic Agents/therapeutic use
KW - Combined Modality Therapy
KW - Double-Blind Method
KW - Female
KW - Humans
KW - Indazoles/adverse effects
KW - Maintenance Chemotherapy
KW - Middle Aged
KW - Nausea/chemically induced
KW - Ovarian Neoplasms/drug therapy
KW - Piperidines/adverse effects
KW - Poly(ADP-ribose) Polymerase Inhibitors/adverse effects
KW - Progression-Free Survival
KW - Quality of Life
KW - Survival Analysis
U2 - 10.1056/NEJMoa1910962
DO - 10.1056/NEJMoa1910962
M3 - Journal article
C2 - 31562799
SN - 0028-4793
VL - 381
SP - 2391
EP - 2402
JO - The New England journal of medicine
JF - The New England journal of medicine
IS - 25
ER -