• J Chris Kingswood, Sergiusz Jozwiak, Elena D Belousova, Michael D Frost, Rachel A Kuperman, E Martina Bebin, Bruce R Korf, J Robert Flamini, Michael H Kohrman, Steven P Sparagana, Joyce Y Wu, Thomas Brechenmacher, Karen Stein, Noah Berkowitz, John J Bissler, and David N Franz.
• Sussex Renal Unit, Royal Sussex County Hospital, Brighton, UK The Trafford Department of Renal Medicine, Royal Sussex County Hospital, Brighton BN2 5BE, UK.
• Nephrol. Dial. Transplant. 2014 Jun 1; 29 (6): 1203-10.

BackgroundTuberous 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.MethodsEXamining 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.ResultsAngiomyolipoma 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).ConclusionsEverolimus 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.© The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

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