Niraparib Improves Progression-Free Survival in Ovarian Cancer, Regardless of BRCA Status

Progression-free survival was improved with niraparib, a PARP inhibitor, in patients with recurrent, platinum-sensitive, high-grade ovarian cancer, regardless of their BRCA status, according to a review of the phase 3 ENGOT-OV16/NOVA that was presented at the 2017 Society of Gynecologic Oncology (SGO) Annual Meeting.

Although patients with BRCA mutations had the best results, those with and without BRCA-mutated disease derived significant benefits from treatment with niraparib. Patients without germline BRCA mutations had a two- to three-fold increase in 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, M.D., director of gynecology and obstetrics at the University of Munich, concluded in his review of the study at the meeting.

“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 of BRCA mutation 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 The New England Journal of Medicine.

The trial involved patients with recurrent, platinum-sensitive high-grade ovarian cancer. Patients with and without BRCA mutations were randomized separately in a 2 to 1 ratio to receive niraparib at 300 mg/day or placebo. Treatment continued until disease progression. Patients without germline BRCA mutations were tested for homologous repair deficiency (HRD).

Data analysis included 203 patients with BRCA mutations and 350 without. The trial had a primary endpoint of PFS.

Patients with BRCA-mutated tumors had a median PFS of 21.0 months with niraparib versus 5.5 months with placebo. The difference translated into a 73 percent reduction in the hazard for progression or survival.

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. The subgroup of patients with HRD-positive tumors had a median PFS of 12.9 months compared with 3.8 months for placebo.

Treatment with niraparib significantly increased the chemotherapy-free interval, regardless of BRCA mutation status: 22.8 versus 9.4 months in BRCA-positive patients; 12.7 versus 8.6 months in the BRCA-negative group; and 18.2 versus 7.7 months in the HRD-positive group.

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 the BRCA-positive group, 11.8 versus 7.2 months for BRCA-negative patients, and 15.9 versus six months for the HRD-positive subgroup.

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 without BRCA mutations 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 percent), anemia (25.3 percent), neutropenia (19.6 percent), fatigue (8.2 percent) and hypertension (8.2 percent). Grade 3/4 AEs from cycle 3 onward were infrequent, the most common being anemia (16.9 percent). Adverse events leading to discontinuation included thrombocytopenia (3.3 percent), fatigue (3.3 percent), neutropenia (1.9 percent), anemia (1.4 percent) and hypertension (0.3 percent).

No grade 3/4 bleeding events occurred and no grade 5 (fatal) AEs occurred during the trial. Hematologic treatment-related AEs 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.