Niraparib Approved by FDA for HRD-Positive Advanced Ovarian Cancer
Posted: Thursday, October 24, 2019
Yesterday, the U.S. Food and Drug Administration (FDA) approved niraparib (Zejula) for patients with advanced ovarian, fallopian tube, or primary peritoneal cancer treated with three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD)-positive status. HRD is defined by either a deleterious or suspected deleterious BRCA mutation or genomic instability in patients with disease progression greater than 6 months after response to the last platinum-based chemotherapy. The FDA also approved the Myriad myChoice CDx test for determination of tumor HRD status to select patients for treatment with niraparib.
Efficacy was investigated in 98 patients with advanced ovarian cancer with HRD-positive tumors in the single-arm QUADRA trial (ClinicalTrials.gov identifier NCT02354586). Patients with prior exposure to PARP inhibitors were excluded. Patients without BRCA mutations must have experienced disease progression at least 6 months after the last dose of platinum-based therapy. HRD-positive status was determined as either tumor BRCA-mutated disease (n = 63) and/or a genomic instability score ≥ 42 (n = 35).
In the 98 patients in the HRD-positive cohort, the objective response rate was 24% (95% confidence interval [CI] = 16%–34%), and all responses were partial. The estimated median duration of response was 8.3 months (95% CI = 6.5 months to not estimable). For patients with tumor BRCA-mutated ovarian cancer, the objective response rate was 39% (95% CI = 17%–64%) in patients with platinum-sensitive disease, 29% (95% CI = 11%–52%) in those with platinum-resistant disease, and 19% (95% CI = 4%–46%) in patients with platinum-refractory disease.
Adverse reactions led to dose reduction or interruption in 73% of patients receiving niraparib in the QUADRA trial. The most common adverse reactions (> 5%) resulting in dose reduction or interruption were thrombocytopenia (40%), anemia (21%), neutropenia (11%), nausea (13%), vomiting (11%), fatigue (9%), and abdominal pain (5%). The recommended dose of niraparib is 300 mg taken once daily with or without food.