• John J Bissler, David N Franz, Michael D Frost, Elena Belousova, E Martina Bebin, Steven Sparagana, Noah Berkowitz, Antonia Ridolfi, and J Christopher Kingswood.
• Division of Nephrology, St Jude Children's Research Hospital and Le Bonheur Children's Hospital, University of Tennessee Health Science Center, 49 North Dunlap Street, Memphis, TN, 38163, USA. jbissler@uthsc.edu.
• Pediatr. Nephrol. 2018 Jan 1; 33 (1): 101-109.

BackgroundPatients with tuberous sclerosis complex (TSC) often have multiple TSC-associated hamartomas, particularly in the brain and kidney.MethodsThis was a post hoc analysis of pediatric patients being treated for subependymal giant cell astrocytomas (SEGAs) during the phase 3, randomized, double-blind, placebo-controlled EXIST-1 trial. Patients were initially randomly assigned to receive everolimus 4.5 mg/m2/day (target blood trough 5-15 mg/dl) or placebo and could continue in an open-label extension phase. Angiomyolipoma response rates were analyzed in patients aged <18 years with ≥1 target angiomyolipoma lesion at baseline. Response was defined as the proportion of patients with a ≥50% reduction in the sum volume of target renal angiomyolipomata from baseline, in the absence of new target angiomyolipomata, a >20% increase in kidney volume from nadir, and angiomyolipoma-related bleeding ≥ grade 2. Tolerability was also assessed.ResultsOverall, this analysis included 33 patients. Renal angiomyolipoma response was achieved by 75.8% of patients (95% confidence interval, 57.7-88.9%), with sustained mean reductions in renal angiomyolipoma volume over nearly 4 years of treatment. In addition, most (≥80%) achieved clinically relevant reductions in angiomyolipoma volume (≥50%), beginning at week 24 and continuing for the remainder of the study. Everolimus was generally well tolerated in this subgroup, with most adverse events being grade 1 or 2 in severity.ConclusionsAlthough everolimus is currently not indicated for this use, this analysis from EXIST-1 demonstrates its long-term efficacy and safety for the treatment of renal angiomyolipoma in pediatric patients undergoing treatment for TSC-associated SEGA.

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