BACKGROUND: Tuberous sclerosis complex (TSC) is characterized by benign tumours 
in multiple organs, including the brain, kidneys, skin, lungs and heart. Our 
objective was to evaluate everolimus, an mTOR inhibitor, in the treatment of 
angiomyolipoma in patients with subependymal giant cell astrocytoma (SEGA) 
associated with TSC.
METHODS: EXamining everolimus In a Study of Tuberous Sclerosis Complex-1 
(NCT00789828), a prospective, double-blind, randomized, placebo-controlled, 
Phase 3 study, examined everolimus in treating SEGA associated with TSC. 
Patients with serial SEGA growth from pre-baseline to baseline scans were 
randomly assigned (2:1) to receive 4.5 mg/m(2)/day everolimus (target blood 
trough: 5-15 ng/mL; n = 78) or placebo (n = 39). Angiomyolipoma response rates 
were analysed in patients (n = 44) with target baseline angiomyolipoma lesions 
(≥1 angiomyolipoma; longest diameter ≥1.0 cm). An angiomyolipoma response rate, 
defined as the proportion of patients with confirmed angiomyolipoma response, 
was assessed by kidney CT or MRI screening at baseline, at 12, 24 and 48 weeks 
and annually.
RESULTS: Angiomyolipoma response rates were 53.3% (16/30) and 0% (0/14) for 
everolimus- and placebo-treated patients, respectively. Angiomyolipoma 
reductions ≥50% in the sum of volumes of all target lesions were seen only in 
everolimus-treated patients (56.5, 78.3 and 80.0%) compared with placebo-treated 
patients (0% at each time point) at Weeks 12, 24 and 48, respectively. Greater 
percentages of everolimus-treated patients had angiomyolipoma reductions ≥30% at 
these same time points (82.6, 100 and 100% versus 8.3, 18.2 and 16.7% for 
everolimus versus placebo, respectively).
CONCLUSIONS: Everolimus showed efficacy in reducing angiomyolipoma lesion volume 
in patients with SEGA associated with TSC.The trial is registered with 
ClinicalTrials.gov, number NCT00789828; 
http://clinicaltrials.gov/ct2/show/NCT00789828?term=EXIST-1&rank=1.