On April 29, 2020, the U.S. Food and Drug Administration (FDA) approved niraparib (Zejula®) for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy.
Efficacy was investigated in a double-blind, placebo-controlled trial (PRIMA; NCT02655016) that randomized 733 patients to niraparib or matched placebo. Eligible patients were in a complete or partial response to first-line platinum-based chemotherapy.
The main efficacy outcome measure was progression-free survival (PFS) and was first tested in the homologous recombination deficient population, then in the overall population. PFS was determined by blinded independent central review per response evaluation criteria in solid tumors 1.1.
Tumor samples were tested for homologous recombination deficiency status, which was defined either by presence of a tumor breast cancer susceptibility gene mutation or genomic instability score ≥ 42. An FDA-approved companion diagnostic is not required to initiate treatment with niraparib for this indication.
The trial demonstrated a statistically significant improvement in PFS for patients randomized to niraparib compared to placebo in the homologous recombination deficient and overall population. Median PFS in the homologous recombination deficient population was 21.9 months (CI = 19.3, not examined) for patients receiving niraparib compared to 10.4 months (CI = 8.1, 12.1) for those receiving placebo (HR = 0.43; 95% CI = 0.31, 0.59; p < 0.0001). Median PFS in the overall population was 13.8 months (CI = 11.5, 14.9) for patients receiving niraparib compared to 8.2 months (CI = 7.3, 8.5) for those receiving placebo (HR = 0.62; 95% CI = 0.50, 0.76; p < 0.0001).
The most common adverse reactions (≥ 10%) for niraparib 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 dose is based on body weight or platelet count. For patients weighing less than 77 kg (170 lbs) or with a platelet count of less than 150,000/mcl, the recommended dose is 200 mg orally once daily. For patients weighing greater than or equal to 77 kg (170 lbs) and who have a platelet count greater than or equal to 150,000/mcl, the recommended dose is 300 mg orally once daily.
View full prescribing information for niraparib.
The review used the Real Time Oncology Review, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment. The application was approved two months prior to FDA’s goal date.
The application was granted priority review. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.
For assistance with single-patient oncology investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.