{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:15:41Z","timestamp":1790720141894,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,11,9]],"date-time":"2015-11-09T00:00:00Z","timestamp":1447027200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Novartis Pharmaceuticals"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>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\u2010label phase II study (NCT00411619). Updated data became available from the conclusion of the extension phase and are presented in this \u22655\u2010year analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients aged\u2009\u2265\u20093 years with a definite diagnosis of TSC and increasing SEGA lesion size (\u22652 magnetic resonance imaging scans) received everolimus starting at 3mg\/m<jats:sup>2<\/jats:sup>\/day (titrated to target blood trough levels of 5\u201315ng\/ml). The primary efficacy endpoint was reduction from baseline in primary SEGA volume.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u201383.2) months; 12 (52.2%) and 14 (60.9%) of 23 patients experienced SEGA volume reductions of \u226550% and \u226530% 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Everolimus continues to demonstrate a sustained effect on SEGA tumor reduction over \u22655 years of treatment. Everolimus remained well\u2010tolerated, and no new safety concerns were noted. 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