Afinitor everolimus: Phase III data

The double-blind, international Phase III EXIST-1 trial in 117 patients showed that Afinitor met the primary endpoint of significantly improving overall SEGA response rate vs. placebo. Specifically, 35% of patients receiving Afinitor (n=78) had a >=50% reduction in SEGA volume from baseline vs. 0% for placebo (n=39; p<0.0001). An analysis of the change in seizure frequency secondary endpoint was inconclusive, which Novartis said may have been due to the method of assessment and the limited number of patients with evaluable seizures at study entry. Based on the results of the seizure frequency endpoint, the statistical plan of the trial did not provide for a formal analysis of subsequent secondary endpoints.

However, a partial clinical response in skin lesions defined as a >=50% improvement was reported in 42% of patients receiving Afinitor vs. 11% for placebo. Furthermore, 0% of patients receiving Afinitor experienced disease progression defined as an increase in SEGA volume, worsening of non-target SEGAs, appearance of new lesions or new hydrocephalus compared to 15% of patients receiving placebo. The median duration of treatment for the Afinitor and placebo arms was 9.6 and 8.3 months, respectively. Data were presented at the International TSC Research meeting in Washington. ...