GlaxoSmithKline plc announced results from PRIMA (ENGOT-OV26/GOG-3012), the Phase 3 randomised, double-blind, placebo-controlled study of Zejula (niraparib) as a maintenance therapy in women with first-line ovarian cancer following response to platinum-based chemotherapy. Niraparib treatment resulted in a 38% reduction in the risk of disease progression or death in the overall population (PFS, HR 0.62; 95% CI, 0.50–0.75; p<0.001).
These results were driven by a clinically meaningful reduction in the risk of progression in women with:
- BRCA mutation tumours (risk reduction of 60%, HR 0.40 (95% CI, 0.27–0.62) p<0.001).
- HR-deficient BRCA wild type tumours (risk reduction of 50%, HR 0.50 (95% CI, 0.30–0.83), p=0.006).
- HR-proficient tumours (risk reduction of 32%, HR 0.68 (95% CI, 0.49–0.94), p=0.020).
The PRIMA study enrolled patients with a response to their first-line treatment with platinum-based chemotherapy including those with a high risk of disease progression, a population with high unmet need and previously under-represented in first-line ovarian cancer studies.
Dr. Hal Barron, Chief Scientific Officer and President R&D, GSK said:
“Ovarian cancer is the eighth most commonly occurring cancer in women worldwide and women with this devastating disease have a five-year survival rate of less than 50%. PRIMA is a landmark study as we believe these data have the potential to fundamentally change how women with ovarian cancer are treated.”
In an interim analysis of overall survival (OS), niraparib also demonstrated an encouraging trend toward improvement in OS relative to placebo. A pre-planned interim analysis of OS numerically favoured niraparib in the overall population (HR 0.70; 95% CI 0.44-1.11). In the HR-deficient subgroup, 91% of women on niraparib were alive at 24 months vs. 85% for placebo (HR=0.61; 95% CI, 0.27-1.40). These data are not yet mature, and the significance is not fully known. The OS interim analysis also showed 81% of women receiving niraparib in the HR-proficient subgroup were alive at 24 months vs. 59% of women receiving placebo (HR=0.51; 95% CI, 0.27-0.97).
Dr. Antonio Gonzalez, co-director, department of medical oncology, Clinica Universidad de Navarra, and Primary Investigator for PRIMA said:
“The PRIMA study demonstrated the importance of maintenance therapy and the benefit that niraparib provided to women with ovarian cancer. I believe that niraparib monotherapy after surgery and platinum-based chemotherapy could be an important new treatment option for patients.”
Niraparib is not currently approved in the first-line ovarian cancer maintenance setting. GSK will share these data with the relevant health authorities and is on track to file by the end of the year.
The safety profile demonstrated in PRIMA did not differ from the established safety profile. The most common grade 3 or higher adverse events with niraparib included anaemia (31%), thrombocytopenia (29%), and neutropenia (13%). Implementation of an individualised dosing regimen based on body weight and/or platelet count reduced the incidence of haematological treatment-emergent adverse events. No new safety signals were identified. The validated patient reported outcomes to indicate the quality of life was similar between the niraparib and placebo treatment arms.
Niraparib is marketed in the United States and Europe under the trade name Zejula®.