Detalle Publicación

Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer

Autores: González Martín, Antonio (Autor de correspondencia); Pothuri, B.; Vergote, I.; Christensen, R. D.; Graybill, W. ; Mirza, M. R. ; McCormick, C. ; Lorusso, D. ; Hoskins, P. ; Freyer, G.; Baumann, K. ; Jardon, K.; Redondo, A. ; Moore, R. G.; Vulsteke, C.; O'Cearbhaill, R. E.; Lund, B. ; Backes, F.; Barretina-Ginesta, P. ; Haggerty, A. F.; Rubio-Perez, M. J.; Shahin, M. S.; Mangili, G. ; Bradley, W. H. ; Bruchim, I. ; Sun, K. ; Malinowska, I. A.; Li, Y.; Gupta, D.; Monk, B. J.
ISSN: 0028-4793
Volumen: 381
Número: 25
Páginas: 2391 - 2402
Fecha de publicación: 2019
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.