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

Web Exclusives —April 30, 2020

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.

Related Articles
Opdivo-Yervoy First Immunotherapy Combo Approved for First-Line Therapy of Patients with Metastatic NSCLC
July 2020 Vol 11, No 7
On May 15, 2020, the FDA approved a new indication for the first immunotherapy combination with the PD-1 inhibitor nivolumab (Opdivo; BMS) and the CTLA-4 inhibitor ipilimumab (Yervoy; BMS) for the first-line treatment of adults with metastatic non–small-cell lung cancer (NSCLC) and PD-L1 expression of ≥1%, as determined by an FDA-approved test, but without EGFR or ALK genomic translocations.
FDA Approves New 400 mg Every-6-Weeks Dosing Regimen of Keytruda for All Indications
Web Exclusives
On April 29, 2020, the FDA accelerated the approval of the oral poly ADP-ribose polymerase (PARP) inhibitor niraparib (Zejula; GlaxoSmithKline) as the first and only drug approved for first-line maintenance therapy of all patients with advanced ovarian cancer—including epithelial ovarian, fallopian tube, or primary peritoneal cancer—who have had a complete or partial response to first-line platinum-based chemotherapy.
Jelmyto First FDA-Approved Therapy for Low-Grade Upper-Tract Urothelial Cancer
Web Exclusives
Last modified: August 10, 2023

Subscribe Today!

To sign up for our print publication or e-newsletter, please enter your contact information below.

I'd like to receive:

  • First Name *
    Last Name *
     
     
    Profession or Role
    Primary Specialty or Disease State
    Country