title: Safety of Everolimus in Patients Younger than 3 Years of Age: Results from EXIST-1, a Randomized, Controlled Clinical Trial.
abstract: To assess the long-term safety of everolimus in young children with tuberous sclerosis complex (TSC)-associated subependymal giant cell astrocytoma (SEGA).
  
  
  
  EXamining everolimus In a Study of Tuberous Sclerosis Complex-1 (EXIST-1) was a multicenter, randomized, double-blind phase 3 study with an open-label extension evaluating the efficacy and tolerability of everolimus in patients with TSC-associated SEGA. Everolimus was initiated at 4.5 mg/m(2)/day and titrated to blood trough levels of 5-15 ng/mL. Post hoc analysis of safety data (adverse events [AEs]) was performed in a subgroup of patients aged <3 years at everolimus initiation.
  
  
  
  Eighteen patients (median age 1.82 years) were included; 16 were still receiving everolimus at the analysis cut-off date of January 11, 2013. Median everolimus exposure was 31.1 months (range, 11.5-39 months). One patient discontinued treatment because of AEs (ie, Acinetobacter bacteremia, increased blood alkaline phosphatase, and viral infection). AEs were reported in all patients, but events were mostly grade 1/2 in severity; 12 patients (66.7%) experienced grade 3 events, and 2 patients (11.1%) reported grade 4 events. The most common AEs were stomatitis, cough, pharyngitis, and pyrexia; no new safety issues were identified in this population. Serious AEs were reported in 50% of patients; these were suspected to be medication related in 4 patients (22.2%).
  
  
  
  Everolimus appears to be a safe therapeutic option for patients aged <3 years with TSC-associated SEGA. The small sample size in this subpopulation limits interpretation of the results; additional studies in the pediatric population are needed and are underway.
  
  
  
  ClinicalTrials.gov: NCT00789828.
authors: Department of Pediatric Neurology, Warsaw Medical University, Warsaw, Poland; Department of Neurology and Epileptology, The Children's Memorial Health Institute, Warsaw, Poland. Electronic address: sergiusz.jozwiak@wum.edu.pl.
authors: Sergiusz
authors: S
authors: Jóźwiak
authors: Department of Neurology and Epileptology, The Children's Memorial Health Institute, Warsaw, Poland.
authors: Katarzyna
authors: K
authors: Kotulska
authors: Department of Oncology, Novartis Pharmaceuticals Corporation, Florham Park, NJ.
authors: Noah
authors: N
authors: Berkowitz
authors: Department of Oncology, Novartis Pharmaceuticals S.A.S., Rueil-Malmaison, France.
authors: Thomas
authors: T
authors: Brechenmacher
authors: Department of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors: David Neal
authors: DN
authors: Franz
mesh_terms: D001254:Astrocytoma / Q000150:complications / Q000188:drug therapy*; D002675:Child, Preschool; D000068338:Everolimus / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007223:Infant; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D016896:Treatment Outcome; D014402:Tuberous Sclerosis / Q000150:complications / Q000188:drug therapy*
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus