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Zejula First PARP Inhibitor Approved as First-Line Maintenance Treatment for All Patients with Ovarian Cancer

Web Exclusives - FDA Approvals, Select Drug Profiles
On April 29, 2020, the FDA accelerated the approval of the oral poly ADP-ribose polymerase (PARP) inhibitor niraparib (Zejula; GlaxoSmithKline) as the first drug approved for first-line maintenance therapy of all patients with advanced ovarian cancer—including epithelial ovarian, fallopian tube, or primary peritoneal cancer—whose cancer has had a complete or partial response to first-line platinum-based chemotherapy. The FDA used its priority review process to accelerate its approval for this new indication.

This approval marks a “simplification of the treatment paradigm,” said Axel Hoos, MD, PhD, SVP and Head of Oncology at GlaxoSmithKline. “Particularly now, in the COVID-19 environment, where it’s harder for patients to go to the doctor and harder to receive an infusion or even do surgery—you just take a pill, and on top of that, you don’t need to undergo testing to find out if you are eligible for this based on mutation. Everyone can benefit,” Dr Hoos noted.

Niraparib was previously approved for maintenance treatment of patients with recurrent ovarian cancer who had a complete or partial response to first-line platinum-based chemotherapy; and for patients with advanced ovarian cancer who received ≥3 chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD)-positive status, defined by the presence of a BRCA mutation or genomic instability (as determined by an FDA-approved test), and disease that progressed >6 months after response to platinum-based chemotherapy.

Since late 2018, women with ovarian cancer whose cancer responded to initial treatment with chemotherapy were eligible to receive treatment with a PARP inhibitor, including niraparib or olaparib (Lynparza), if their cancer was associated with a BRCA mutation, as determined by an FDA-approved test.

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.

The study results, which were presented in September 2019 at the European Society for Medical Oncology annual meeting, indicated an overall 38% risk reduction for disease progression or death with niraparib compared with placebo as first-line maintenance for all patients with ovarian cancer, regardless of mutation status.

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 and was determined by an independent central review per RECIST 1.1. The tumor samples were tested for HRD status, which was defined by either presence of tumor breast cancer susceptibility gene (BRCA) mutation or by genomic instability score ≥42.

Specifically, 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 (≥10%) adverse reactions with niraparib in the PRIMA study were thrombocytopenia, anemia, nausea, fatigue, neutropenia, constipation, musculoskeletal pain, leukopenia, headache, insomnia, vomiting, dyspnea, decreased appetite, dizziness, cough, hypertension, AST/ALT elevation, and acute kidney injury.

The recommended niraparib dose for first-line maintenance treatment of advanced ovarian cancer is based on body weight or platelet count.

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Last modified: August 30, 2021