The effect of everolimus on renal angiomyolipoma in pediatric patients with tuberous sclerosis being treated for subependymal giant cell astrocytoma.

Abstract

BACKGROUND:

Patients with tuberous sclerosis complex (TSC) often have multiple TSC-associated hamartomas, particularly in the brain and kidney.

METHODS:

This 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.

RESULTS:

Overall, 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.

CONCLUSIONS:

Although 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.

• Authors: John J Bissler, David N Franz, Michael D Frost, Elena Belousova, E Martina Bebin, Steven Sparagana, Noah Berkowitz, Antonia Ridolfi, J Christopher Kingswood
• Journal: Pediatric nephrology (Berlin, Germany) (Pediatr Nephrol) Vol. 33 Issue 1 Pg. 101-109 (Jan 2018) ISSN: 1432-198X [Electronic] Germany
• PMID: 28993887 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• Antineoplastic Agents
• Everolimus

Topics

• Adolescent
• Angiomyolipoma (complications, drug therapy)
• Antineoplastic Agents (adverse effects, therapeutic use)
• Astrocytoma (complications, drug therapy)
• Child
• Child, Preschool
• Double-Blind Method
• Everolimus (adverse effects, therapeutic use)
• Female
• Humans
• Kidney (pathology)
• Kidney Neoplasms (drug therapy, pathology)
• Male
• Treatment Outcome
• Tuberous Sclerosis (complications, drug therapy)