title: Everolimus for subependymal giant cell astrocytoma: 5-year final analysis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Departments of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.|Departments of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: David N
authors.initials: DN
authors.lastname: Franz
authors.affiliation: Departments of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.|Departments of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Karen
authors.initials: K
authors.lastname: Agricola
authors.affiliation: Departments of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.|Departments of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Maxwell
authors.initials: M
authors.lastname: Mays
authors.affiliation: Departments of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.|Departments of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Cindy
authors.initials: C
authors.lastname: Tudor
authors.affiliation: Departments of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.|Departments of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Marguerite M
authors.initials: MM
authors.lastname: Care
authors.affiliation: Departments of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.|Departments of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Katherine
authors.initials: K
authors.lastname: Holland-Bouley
authors.affiliation: Department of Oncology, Novartis Pharmaceuticals Corporation, East Hanover, NJ.
authors.forename: Noah
authors.initials: N
authors.lastname: Berkowitz
authors.affiliation: Department of Oncology, Novartis Pharmaceuticals Corporation, East Hanover, NJ.
authors.forename: Sara
authors.initials: S
authors.lastname: Miao
authors.affiliation: Department of Oncology, Novartis Pharmaceuticals, Rueil-Malmaison, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Peyrard
authors.affiliation: Departments of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.|Departments of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Darcy A
authors.initials: DA
authors.lastname: Krueger
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001254:Astrocytoma / Q000188:drug therapy* / Q000209:etiology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D000068338:Everolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D017063:Outcome Assessment, Health Care; D014402:Tuberous Sclerosis / Q000150:complications*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D000068338:Everolimus