• Darcy A Krueger, Marguerite M Care, Karen Agricola, Cindy Tudor, Maxwell Mays, and David Neal Franz.
• Department of Pediatrics and Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
• Neurology. 2013 Feb 5; 80 (6): 574-80.

ObjectiveTo report long-term efficacy and safety data for everolimus for the treatment of subependymal giant cell astrocytoma (SEGA) in patients with tuberous sclerosis complex (TSC).MethodsThis was an open-label extension phase of a prospective, phase 1-2 trial (NCT00411619) in patients ≥3 years of age with SEGA associated with TSC. Patients received oral everolimus starting at 3 mg/m2 per day and subsequently titrated, subject to tolerability, to attain whole blood trough concentrations of 5-15 ng/mL. Change in SEGA volume, seizures, and safety assessments were the main outcome measures.ResultsOf 28 patients enrolled, 25 were still under treatment at the time of analysis. Median dose was 5.3 mg/m2/day and median treatment duration was 34.2 months (range 4.7-47.1). At all time points (18, 24, 30, and 36 months), primary SEGA volume was reduced by ≥30% from baseline (treatment response) in 65%-79% of patients. All patients reported ≥1 adverse event (AE), mostly grade 1/2 in severity, consistent with that previously reported, and none led to everolimus discontinuation. The most commonly reported drug-related AEs were upper respiratory infections (85.7%), stomatitis (85.7%), sinusitis (46.4%), and otitis media (35.7%). No drug-related grade 4 or 5 events occurred.ConclusionEverolimus therapy is safe and effective for longer term (median exposure 34.2 months) treatment of patients with TSC with SEGA.Classification Of EvidenceThis study provides Class III evidence that everolimus, titrated to trough serum levels of 5-15 ng/mL, was effective in reducing tumor size in patients with SEGA secondary to TSC for a median of 34 months.

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