On October 23, 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–positive status. Homologous recombination deficiency 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.
Efficacy was investigated in 98 patients with advanced ovarian cancer and homologous recombination deficiency–positive tumors in the single-arm QUADRA trial. Patients were treated with three or more prior lines of chemotherapy. Those with prior exposure to poly (ADP-ribose) polymerase inhibitors were excluded. Patients without BRCA mutations must have had disease progression at least 6 months after the last dose of platinum-based therapy.
Homologous recombination deficiency–positive status was determined using the Myriad myChoice CDx as either tumor BRCA-mutated (n = 63) and/or a genomic instability score ≥ 42 (n = 35). All patients received 300 mg of niraparib once daily until disease progression or unacceptable toxicity.
The primary efficacy outcome measures were objective response rate and duration of response as assessed by the investigator using Response Evaluation Criteria in Solid Tumors, version 1.1. In the 98 patients in the homologous recombination deficiency–positive cohort, the objective response rate was 24% (95% confidence interval [CI] = 16%–34%). All were partial responses. The estimated median duration of response was 8.3 months (95% CI = 6.5–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 QUADRA. 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 niraparib dose is 300 mg taken once daily with or without food. Patients should be selected for therapy based on an FDA-approved companion diagnostic for niraparib. View the full prescribing information for niraparib.