Everolimus long-term safety and efficacy in subependymal giant cell astrocytoma

Objective: To 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). Methods: This 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/m 2 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. Results: Of 28 patients enrolled, 25 were still under treatment at the time of analysis. Median dose was 5.3 mg/m 2 /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. Conclusion: Everolimus therapy is safe and effective for longer term (median exposure 34.2 months) treatment of patients with TSC with SEGA. Classification of evidence: This 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.