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Ann Neurol. 2015 Dec;78(6):929-38. doi: 10.1002/ana.24523. Epub 2015 Nov 9.

Everolimus for subependymal giant cell astrocytoma: 5-year final analysis.

Author information

1
Departments of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
2
Departments of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
3
Departments of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
4
Department of Oncology, Novartis Pharmaceuticals Corporation, East Hanover, NJ.
5
Department of Oncology, Novartis Pharmaceuticals, Rueil-Malmaison, France.

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.

INTERPRETATION:

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.

PMID:
26381530
PMCID:
PMC5063160
DOI:
10.1002/ana.24523
[Indexed for MEDLINE]
Free PMC Article

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