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J Pediatr. 2016 May;172:151-155.e1. doi: 10.1016/j.jpeds.2016.01.027. Epub 2016 Feb 6.

Safety of Everolimus in Patients Younger than 3 Years of Age: Results from EXIST-1, a Randomized, Controlled Clinical Trial.

Author information

1
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.
2
Department of Neurology and Epileptology, The Children's Memorial Health Institute, Warsaw, Poland.
3
Department of Oncology, Novartis Pharmaceuticals Corporation, Florham Park, NJ.
4
Department of Oncology, Novartis Pharmaceuticals S.A.S., Rueil-Malmaison, France.
5
Department of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.

Abstract

OBJECTIVES:

To assess the long-term safety of everolimus in young children with tuberous sclerosis complex (TSC)-associated subependymal giant cell astrocytoma (SEGA).

STUDY DESIGN:

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.

RESULTS:

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%).

CONCLUSIONS:

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.

TRIAL REGISTRATION:

ClinicalTrials.gov: NCT00789828.

PMID:
26858193
DOI:
10.1016/j.jpeds.2016.01.027
[Indexed for MEDLINE]

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