Everolimus for Subependymal Giant Cell Astrocytoma: 5-Year Final Analysis

Objective: To analyze the cumulative efficacy and safety of everolimus in treating subependymal giant cell astrocytomas (SEGA) associated with tuberous sclerosis complex (TSC) from an open-label phase II study (NCT00411619). Updated data became available from the conclusion of the extension phase and are presented in this >= 5-year analysis. Methods: Patients aged >= 3 years with a definite diagnosis of TSC and increasing SEGA lesion size (>= 2 magnetic resonance imaging scans) received everolimus starting at 3mg/m(2)/day (titrated to target blood trough levels of 5-15ng/ml). The primary efficacy endpoint was reduction from baseline in primary SEGA volume. Results: As of the study completion date (January 28, 2014), 22 of 28 (78.6%) initially enrolled patients finished the study per protocol. Median (range) duration of exposure to everolimus was 67.8 (4.7-83.2) months; 12 (52.2%) and 14 (60.9%) of 23 patients experienced SEGA volume reductions of >= 50% and >= 30% relative to baseline, respectively, after 60 months of treatment. The proportion of patients experiencing daily seizures was reduced from 7 of 26 (26.9%) patients at baseline to 2 of 18 (11.1%) patients at month 60. Most commonly reported adverse events (AEs) were upper respiratory tract infection and stomatitis of mostly grade 1 or 2 severity. No patient discontinued treatment due to AEs. The frequency of emergence of most AEs decreased over the course of the study. Interpretation: Everolimus continues to demonstrate a sustained effect on SEGA tumor reduction over >= 5 years of treatment. Everolimus remained well-tolerated, and no new safety concerns were noted.