Abstract Details

Title Effect of Everolimus on Subependymal Nodules (SENs) and Tubers in Patients with Subependymal Giant Cell Astrocytoma (SEGA) Associated with Tuberous Sclerosis Complex (TSC): Results from the EXIST-1 Trial

Topic Neurotoxicology

Presentation(s) P01 - (-)

Poster/Presentation
Number 049

Objective

Background TSC results in nonmalignant tumor growth throughout the body. In the brain, SENs, tubers, and SEGAs result in neurobehavioral and neurocognitive abnormalities, as well as epilepsy.

Design/Methods EXIST-1 (NCT00789828), a prospective, double-blind, randomized, placebo-controlled, phase 3 study, demonstrated a statistically significant difference (p< 0.0001) in the overall SEGA response rate in favor of everolimus (34.6% versus 0%) with an acceptable safety profile. Patients were randomized (2:1) to receive everolimus (n=78) or placebo (n=39) stratified by use of enzyme-inducing antiepileptic drugs. Everolimus was initiated at 4.5 mg/m[sup2]/day orally, titrated (trough concentrations 5-15 ng/mL) based on tolerability. Change in SEN and tuber lesion volumes were exploratory analyses.

Results Median (range) baseline SEN and tuber volumes were 0.88 cm[sup3] (0.10, 6.0) and 26.4 cm[sup3] (0.8, 158.9). After 12, 24, and 48 weeks of everolimus treatment, the percentage change from baseline (range) in the median sums of SEN volumes were -25.9% (-63.9%, 37.0%), -35.4% (-79.0%, 121.9%), and -35.3% (-79.9%, 23.8%) compared with placebo -13.5% (-36.1%, 13.4%), -12.4% (-45.4%, 16.1%), and 6.6% (-19.4%, 17.4%), respectively. At these same time points, the percentage change from baseline (range) in the median sums of tuber volumes were -2.4% (-68.1%, 59.1%), -5.5% (-67.5%, 46.6%), and 0.07% (-72.3%, 59.9%) in the everolimus arm compared with 1.9% (-32.6%, 45.3%), -2.7% (-41.8%, 85.2%), and -8.7% (-46.9%, 37.3%) in the placebo arm, respectively. Adverse events remained similar to those previously reported for everolimus, mostly grade 1/2.

Conclusions A possible trend towards shrinkage of SENs was observed with minimal change in tuber volume. No clear effect of everolimus on reducing the volumes of SENs and tubers was noted due to the high variability in percentage change observed for both treatment arms.

Authors/Disclosures
David N. Franz, MD (CCHMC/MLC 2015) PRESENTER	No disclosure on file
Samuel Goldlust, MD (John Theruer Cancer Center)	No disclosure on file
	No disclosure on file
	No disclosure on file
Sergiusz Jozwiak	No disclosure on file

��ɫ��

��ɫ��