The oral poly ADP-ribose polymerase (PARP) inhibitor niraparib (Zejula; GlaxoSmithKline) has received a new indication from the US Food and Drug Administration (FDA), which granted approval to the drug for the maintenance treatment of women with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who achieved a complete or partial response to first-line platinum-based chemotherapy.
The FDA approved this new indication for niraparib as first-line maintenance therapy for all women with ovarian cancer based on the PRIMA study, a double-blind, placebo-controlled randomized clinical trial. PRIMA included 733 patients with ovarian cancer who had a complete or partial response to first-line treatment with platinum-based chemotherapy; patients were randomized to receive niraparib or matched placebo. Niraparib was initially dosed at 300 mg/day, but the protocol was amended to allow a dose of 200 mg/day in patients with a low baseline body weight (<77 kg) or low platelet count (<150,000/μL).
All patients enrolled in PRIMA had newly diagnosed advanced high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube cancer. Patients were considered high risk in that they were required to have visible residual disease after debulking surgery. Patients whose cancer was associated with homologous recombination deficiency (HRD)-positive status, defined by the presence of a BRCA mutation or genomic instability, were eligible for enrollment.
The main efficacy outcome measure of the PRIMA study was progression-free survival (PFS), which was first tested in patients with HRD-positive disease and then in the overall population. The tumor samples were tested for HRD status, which was defined by either the presence of tumor breast cancer susceptibility gene (BRCA) mutation or by genomic instability score ≥42.
The results showed significant improvement in PFS among patients who received niraparib compared with those who received placebo in patients with and without HRD-positive status. The median PFS in HRD-related patients was 21.9 months (95% confidence interval [CI], 19.3-not estimable) with niraparib compared with 10.4 months (95% CI, 8.1-12.1) with placebo (hazard ratio [HR], 0.43; 95% CI, 0.31-0.59; P <.0001). The median PFS in the overall population was 13.8 months (95% CI, 11.5-14.9) with niraparib versus 8.2 months (95% CI, 7.3- 8.5) with placebo (HR, 0.62; 95% CI, 0.50-0.76; P <.0001). The most common grade ≥3 adverse reactions with niraparib in the PRIMA study were anemia (31%), thrombocytopenia (28.7%), and neutropenia (12.8%). Dose reductions were necessary in 70.9% of patients treated with niraparib, and 12% of patients in the niraparib arm versus 2.5% in the placebo arm discontinued treatment because of adverse events.
In summary, among patients with newly diagnosed advanced ovarian cancer, those who received niraparib after responding to platinum-based chemotherapy had significantly longer PFS than patients receiving placebo. Adverse event rates were consistent with the class effects previously observed in PARP inhibitors.