Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer

Abstract

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.)

Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial

“…22 Additionally, the NOVA trial (NCT01847274) prospectively tested a homologous recombination defi ciency-based assay in a trial of niraparib as maintenance therapy in patients with platinum-sensitive ovarian cancer. 37 However, to our knowledge, ARIEL2 is the only study to prospectively assess a homologous recombination defi ciency assay in patients with ovarian cancer who have measurable disease treated with a PARP inhibitor, thereby testing the assay as a biomarker for PARP inhibitor response. Other prospective trials in ovarian cancer are assessing homologous recombination defi ciency assays in the maintenance setting following platinum therapy (eg, NOVA and ARIEL3 [NCT01968213]).…”

Recommendations for biomarker testing in epithelial ovarian cancer: a National Consensus Statement by the Spanish Society of Pathology and the Spanish Society of Medical Oncology

“…Data from the phase III NOVA niraparib maintenance study [53], which has a similar design to Study 19, have confirmed the significant progression-free survival benefit among patients with a germline mutation (21.0 vs 5.5 months), which resembles that obtained among patients with a somatic mutation (20.0 vs 11.0 months). Patients without a BRCA mutation were included and stratified according to whether the HRD test was positive.…”

Molecular Chemotherapies in Gynecologic

“…Also shown in Table 1 are the studies upon which FDA approval was based. Of note, the more recent agents have received special designations for accelerated approval, and are no longer necessarily subject to the typical FDA requirement of having completed two Phase III clinical trials [15]. Side effects of these agents include nausea, vomiting, fatigue, anemia, thrombocytopenia, myelodysplastic syndrome, and acute myeloid leukemia.…”