Scientific publications
Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer
Antonio González-Martín, M.D., Ph.D., Bhavana Pothuri, M.D., Ignace Vergote, M.D., Ph.D., René DePont Christensen, Ph.D., Whitney Graybill, M.D., Mansoor R. Mirza, M.D., Colleen McCormick, M.D., M.P.H., Domenica Lorusso, M.D., Ph.D., Paul Hoskins, M.D., Gilles Freyer, M.D., Klaus Baumann, M.D., Kris Jardon, M.D., et al., for the PRIMA/ENGOT-OV26/GOG-3012 Investigators*
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. opens in new tab.)
CITATION N Engl J Med. 2019 Dec 19;381(25):2391-2402.
doi: 10.1056/NEJMoa1910962. Epub 2019 Sep 28.
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