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SGO 2017: Secondary Endpoint Results of Phase III ENGOT-OV16/NOVA Trial of Niraparib in Recurrent Ovarian Cancer

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Key Points

  • Among patients who were germline BRCA mutation carriers, the median chemotherapy-free interval for those treated with niraparib was 22.8 months, compared to 9.4 months for control. Among patients without germline BRCA mutations, the median chemotherapy-free interval for patients treated with niraparib was 12.7 months, compared to 8.6 months for control.
  • Among patients who were germline BRCA mutation carriers, the median time to first subsequent treatment for patients treated with niraparib was 21.0 months, compared to 8.4 months for control. Among non–germline BRCA mutation carrier patients, the median time to first subsequent treatment for patients treated with niraparib was 11.8 months, compared to 7.2 months for control.
  • Progression-free survival 2 data were statistically significant and favored niraparib over control for patients in both cohorts.

Secondary endpoint results from the phase III ENGOT-OV16/NOVA trial of niraparib were presented at the 2017 Society for Gynecologic Oncology (SGO) Annual Meeting on Women's Cancer, by Sven Mahner, MD, Director, Department of Gynecology and Obstetrics, University of Munich.

“The results of several secondary endpoints from the ENGOT-OV16/NOVA trial, including chemotherapy-free interval, time to second subsequent therapy, and progression-free survival 2, demonstrate the positive and durable treatment effect of niraparib in a broad population of patients with ovarian cancer, regardless of germline BRCA mutation status,” said Mary Lynne Hedley, PhD, President and COO of Tesaro. “An assessment of progression-free survival in patients who have progressed on treatment received after completing the NOVA study treatment compared to their first progression while on the NOVA study indicates that niraparib does not decrease the benefit of subsequent treatment.”

Niraparib is the only poly ADP ribose polymerase inhibitor that has shown a clinically meaningful increase in progression-free survival in women with recurrent ovarian cancer, regardless of BRCA mutation or biomarker status, in a randomized, prospectively designed phase III clinical trial.

Secondary Endpoint Results

• Niraparib Significantly Improved Chemotherapy-Free Interval

Among patients who were germline BRCA mutation carriers, the niraparib arm successfully achieved statistical significance over the control arm for the secondary endpoint of chemotherapy-free interval, with a hazard ratio (HR) of 0.26 (95% CI = 0.166–0.409). The median chemotherapy-free interval for patients treated with niraparib was 22.8 months, compared to 9.4 months for control (< .0001).

Among patients without germline BRCA mutations, the niraparib arm successfully achieved statistical significance over the control arm for the secondary endpoint of chemotherapy-free interval, with a hazard ratio of 0.50 (95% CI = 0.370–0.666). The median chemotherapy-free interval for patients treated with niraparib was 12.7 months, compared to 8.6 months for control (< .0001).

• Niraparib Significantly Improved Time to First Subsequent Treatment

Among patients who were germline BRCA mutation carriers, the niraparib arm successfully achieved statistical significance over the control arm for the secondary endpoint of time to first subsequent treatment, with a hazard ratio of 0.31 (95% CI = 0.205–0.481). The median time to first subsequent treatment for patients treated with niraparib was 21.0 months, compared to 8.4 months for control (< .0001).

Among non–germline BRCA mutation carriers, the niraparib arm successfully achieved statistical significance over the control arm for the secondary endpoint of time to first subsequent treatment, with a hazard ratio of 0.55 (95% CI = 0.412–0.721). The median time to first subsequent treatment for patients treated with niraparib was 11.8 months, compared to 7.2 months for control (< .0001).

• Niraparib Had No Impact on the Efficacy of Next-Line Therapy

For a pooled group of patients who have progressed on subsequent therapy (including patients with germline BRCA mutations and without germline BRCA mutations), each patient's initial progression-free survival interval was subtracted from the progression-free survival 2 interval, which showed no reduction in benefit of niraparib treatment on the effectiveness of subsequent chemotherapy, with a hazard ratio of 1.02 (95% CI = 0.76–1.349). In the NOVA study, a hazard ratio of 1.0 demonstrates that the impact of niraparib on efficacy of the subsequent therapy was clinically indistinguishable from the impact of placebo control on the efficacy of the subsequent therapy.

• Progression-Free Survival 2 and Overall Survival are Immature, but Favor Niraparib

Progression-free survival 2 data were statistically significant and favored niraparib over control for patients in both the germline BRCA mutation cohort (HR = 0.48; 95% CI = 0.242­–0.687) and non–germline BRCA mutation cohort (HR = 0.69; 95% CI = 0.494–0.964). Given the relatively long progression-free survival patients experienced on niraparib, progression-free survival 2 was immature, with only 30% of events captured for patients in the germline BRCA mutation cohort and only 50% of events captured for patients in the non–germline BRCA mutation cohort. Data for overall survival were also immature (HR = 0.73; 95% CI = 0.480 to 1.125; = .1545), as fewer than 20% of events had occurred at the time of analysis.

Phase III ENGOT-OV16/NOVA Trial Results

The ENGOT-OV16/NOVA trial is an international phase III, double-blind, placebo-controlled study that enrolled 553 patients with recurrent ovarian cancer who had achieved either a partial or complete response to their most recent platinum-based chemotherapy. Niraparib significantly increased progression-free survival in patients with and without germline BRCA mutations as compared to control, and the magnitude of benefit was similar for patients entering the trial with a partial or complete response. Results also showed that treatment with niraparib reduced the risk of disease progression or death by 73% in patients with germline BRCA mutations (HR = 0.27) and by 55% in patients without germline BRCA mutations (HR = 0.45).

The most common grade 3/4 adverse reactions to niraparib in the NOVA trial included thrombocytopenia (29%), anemia (25%), neutropenia (20%), and hypertension (9%). The majority of hematologic adverse events were managed via dose modification. Discontinuation of therapy due to thrombocytopenia, neutropenia, and anemia occurred in 3.3%, 1.9%, and 1.4% of patients, respectively.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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