This agent was originally approved in March 2017 for women with recurrent ovarian cancer. Until now, only 20% of women with ovarian cancer, those with a BRCA mutation (BRCAm), were qualified to be treated with a PARP inhibitor as monotherapy in the first-line maintenance setting. This latest approval for niraparib makes it the only oral monotherapy available as first-line maintenance treatment for women regardless of BRCA mutational status, addressing a large, unmet need in the ovarian cancer patient population. The results of the PRIMA study were previously presented at the 2019 European Society for Medical Oncology Congress and published in the New England Journal of Medicine.
The approval of the expanded indication was based on the phase III PRIMA study (ENGOT-OV26/GOG-3012). The PRIMA (NCT02655016) study was a multicenter, double-blind, placebo-controlled phase III trial that randomized 733 patients to niraparib or matched placebo. Patients were in a complete or partial response to first-line, platinum-based chemotherapy. The primary endpoint in the PRIMA study was progression-free survival (PFS) analyzed sequentially, first in the homologous recombination deficient (HRd) population, then in the overall population.
The PRIMA study significantly enhanced PFS for patients treated with niraparib, regardless of biomarker status. In the HRd population, niraparib resulted in a 57% reduction in the risk of disease progression or death versus placebo (HR, 0.43; 95% CI, 0.31-0.59; P <.0001), and a 38% reduction in the risk of disease progression or death versus placebo in the overall population (HR, 0.62; 95% CI, 0.50-0.76; P <.0001). At the 24-month interim analysis, the rate of overall survival was 84% in the niraparib group and 77% in the placebo group (HR, 0.70; 95% CI, 0.44-1.11). At initiation of the PRIMA study, patients received a fixed starting dose of 300 mg of niraparib once daily.
The study was later amended to incorporate an individualized starting dose of either 200 mg or 300 mg of niraparib once daily based on the patient’s baseline weight and/or platelet count. Lower rates of grade 3 and 4 hematologic treatment-emergent adverse events were observed with an individualized starting dose, compared with the overall population, including thrombocytopenia (21% compared with 39%), anemia (23% compared with 31%), and neutropenia (15% compared with 21%).
The study concluded that among patients with newly diagnosed advanced ovarian cancer who had a response to platinum-based chemotherapy, those who received niraparib had considerably longer PFS than those who received placebo, regardless of the presence or absence of homologous-recombination deficiency. The U.S. prescribing information has been updated to include the individualized starting dose of 200 mg or 300 mg once daily based on patients’ baseline weight and/or platelet count for the first-line maintenance treatment indication. The starting dose for recurrent ovarian cancer and late-line treatment settings is 300 mg once daily.
