The FDA approved a new indication for niraparib (Zejula, GlaxoSmithKline), an oral, once-daily poly (ADP-ribose) polymerase (PARP) inhibitor, as a monotherapy maintenance treatment for women with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy, regardless of biomarker status. 

Niraparib is the only once-daily PARP inhibitor approved in the United States as monotherapy for women with advanced ovarian cancer beyond those with BRCAm disease in the first-line and recurrent maintenance treatment settings, as well as late-line primary treatment settings.

This new indication is supported by data from the phase 3 PRIMA study, which enrolled patients with newly diagnosed advanced ovarian cancer following a complete or partial response to platinum-based chemotherapy regardless of biomarker status. The PRIMA study enrolled women with a higher risk for disease progression, a group with limited treatment options.

“PRIMA was designed for patients with ovarian cancer who have a high unmet need. The positive data observed regardless of biomarker status in this study is extremely encouraging and suggests benefit beyond the BRCAm population. This approval is an important step forward in the treatment of ovarian cancer. In my opinion, maintenance treatment with niraparib should be considered an option for appropriate patients who responded to first-line platinum-based chemotherapy versus active surveillance,” said Bradley Monk, MD, the PRIMA investigator, with US Oncology, University of Arizona College of Medicine, and Creighton University School of Medicine at St. Joseph’s Hospital, in  Phoenix.

The primary end point in the PRIMA study was progression-free survival (PFS) analyzed sequentially, first in the homologous recombination-deficient (HRd) group, then in the overall population. The PRIMA study found significantly improved PFS in patients treated with niraparib, regardless of biomarker status. In the HRd population, niraparib resulted in a 57% reduction in the risk for disease progression or death compared with placebo (hazard ratio [HR], 0.43; 95% CI, 0.31-0.59; P<0.0001), and a 38% reduction in the risk for disease progression or death versus placebo in the overall population (HR, 0.62; 95% CI, 0.50-0.76; P<0.0001) (N Engl J Med 2019;381[25]:2391-2402).

Niraparib’s safety profile, as demonstrated by the PRIMA results, was consistent with clinical trial experience. The most common grade 3 or higher adverse events with niraparib included thrombocytopenia, anemia and neutropenia.

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 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-related adverse events were observed with an individualized starting dose compared with the overall population, including thrombocytopenia (21% vs. 39%), anemia (23% vs. 31%), and neutropenia (15% vs. 21%).

The package insert has been updated to include the individualized starting dose of 200 or 300 mg once daily based on the patient’s 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.

—Clinical Oncology News Staff

Based on company press materials from GlaxoSmithKline.