BACKGROUNDNiraparib 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. METHODSIn 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. RESULTSOf 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. CONCLUSIONSAmong patients with platinum-sensitive, recurrent ovarian cancer, the median duration of progression-free survival was significantly longer among those 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.)

Olaparib as maintenance treatment significantly improved progression-free survival among patients with platinum-sensitive, relapsed, high-grade serous ovarian cancer. Interim analysis showed no overall survival benefit. The toxicity profile of olaparib in this population was consistent with that in previous studies. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT00753545.).

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Ovarian cancer is not a single disease and can be subdivided into at least five different 2 histological subtypes that have different identifiable risk factors, cells of origin, molecular compositions, clinical features and treatments. Ovarian cancer is a global problem, is typically diagnosed at late stage, and has no effective screening strategy. Standard treatments for newly diagnosed cancer consist of cytoreductive surgery and platinum-based chemotherapy. In recurrent cancer, chemotherapy, anti-angiogenic agents, and poly (ADP ribose) polymerase (PARP) inhibitors are used and immunological therapies are currently being tested. High-grade serous carcinoma (HGSC) is the most commonly diagnosed form of ovarian cancer and is typically very responsive to platinum-based chemotherapy at diagnosis. However, in addition to the other histologies, HGSCs frequently relapse and become increasingly resistant to chemotherapy.Consequently, understanding the mechanisms underlying platinum resistance and finding ways to overcome them are active areas of study in ovarian cancer. Significant progress has been made in identifying genes associated with high risk of ovarian cancer (such as BRCA1 and BRCA2) as well as a precursor lesion of HGSC called a serous tubal intraepithelial carcinoma, which hold promise for identifying individuals at high risk of developing the disease and for developing prevention strategies. Competing interestsU.A.M. has served as a consultant for AstraZeneca, ImmunoGen, Pfizer, Genentech, and Merck.