Results of a recent phase III trial suggested that the PARP inhibitor niraparib warrants consideration for patients with recurrent, platinum-sensitive, high-grade ovarian cancer, irrespective of <em>BRCA</em> status, a reviewer of the study concluded.
Sven Mahner, MD
Results of a recent phase III trial suggested that the PARP inhibitor niraparib warrants consideration for patients with recurrent, platinum-sensitive, high-grade ovarian cancer, irrespective ofBRCAstatus, a reviewer of the study concluded.
Although patients withBRCA-mutated disease had the best results, patients with and withoutBRCA-mutated disease derived significant benefits from treatment with niraparib. Patients without germlineBRCAmutations had a 2- to 3-fold increase in progression-free survival (PFS) with niraparib versus placebo.
Results of the ENGOT-OV16/NOVA trial showed significant improvement in all of the key secondary endpoints, in addition to the primary endpoint of PFS, Sven Mahner, MD, director of gynecology and obstetrics at the University of Munich, concluded in a review at the Society of Gynecologic Oncology meeting in National Harbor, MD.
“Niraparib had no impact on the efficacy of the next line of therapy, suggesting a prolonged clinical benefit,” Mahner said. “No detrimental effect on quality of life was observed with niraparib. Based on these findings, niraparib should be considered for patients with recurrent, high-grade ovarian cancer responding to platinum-based chemotherapy, irrespective ofBRCAmutation status.”
Reviewed as part of a seminal abstract session at the SGO meeting, results of the ENGOT-OV16/NOVA trial initially were reported last October at the European Society for Medical Oncology conference. The results were published simultaneously in theNew England Journal of Medicine.
The trial involved patients with recurrent, platinum-sensitive high-grade ovarian cancer. Patients with and withoutBRCAmutations randomized separately 2:1 to receive niraparib 300 mg/day or placebo. Treatment continued until disease progression. Patients without germlineBRCAmutations were tested for homologous repair deficiency (HRD).
Data analysis included 203 patients withBRCAmutations and 350 without. The trial had a primary endpoint of PFS.
Patients withBRCA-mutated tumors had a median PFS of 21.0 months with niraparib versus 5.5 months with placebo. The difference translated into a 73% reduction in the hazard for progression or survival (P <0.0001).
In the overall analysis of patients with non-mutated disease, treatment with niraparib led to a median PFS of 9.3 months versus 3.9 months with placebo (HR 0.45, P <0.0001). The subgroup of patients with HRD-positive tumors had a median PFS of 12.9 months compared with 3.8 months for placebo (HR 0.38, P <0.0001).
Treatment with niraparib significantly increased the chemotherapy-free interval, regardless ofBRCAmutation status: 22.8 versus 9.4 months in theBRCA-positive patients (HR 0.27, P <0.0001); 12.7 versus 8.6 months in theBRCA-negative group (HR 0.50, P <0.0001); and 18.2 versus 7.7 months in the HRD-positive group (HR 0.31, P <0.0001).
Similar results in favor of niraparib emerged from an analysis of the secondary endpoint of time to first subsequent treatment: 21.0 versus 8.4 months for theBRCA-positive group, 11.8 versus 7.2 months forBRCA-negative patients, and 15.9 versus 6.0 months for the HRD-positive subgroup (P <0.0001 for all comparisons).
Data remain immature for other secondary endpoints, Mahner said. However, preliminary analyses all favored niraparib treatment, including PFS2 (after first subsequent treatment), time to second subsequent treatment, and overall survival.
A comparison of PFS2 and PFS1 for patients with and withoutBRCAmutations showed no impact of niraparib treatment on the efficacy of next-line therapy, Mahner said.
The most common grade 3/4 adverse events (AEs) in patients treated with niraparib were thrombocytopenia (33.8%), anemia (25.3%), neutropenia (19.6%), fatigue (8.2%), and hypertension (8.2%). Grade 3/4 adverse events from cycle 3 onward were infrequent, the most common being anemia (16.9%). Adverse events leading to discontinuation included thrombocytopenia (3.3%), fatigue (3.3%), neutropenia (1.9%), anemia (1.4%), and hypertension (0.3%).
No grade 3/4 bleeding events occurred and no grade 5 (fatal) AEs occurred during the trial. Hematologic treatment-related adverse events were manageable through dose individualization, Mahner said.
Quality of life (QoL) was assessed at different intervals by means of an ovarian cancer-specific instrument and a more general health-related QoL survey.
“Patient-reported outcomes were similar for niraparib and placebo through the study,” Mahner said.