The effect of everolimus on renal angiomyolipoma in patients with tuberous sclerosis complex being treated for subependymal giant cell astrocytoma: Subgroup results from the randomized, placebo-controlled, Phase 3 trial EXIST-1

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, David N. Franz

Research output: Contribution to journalArticle

55 Scopus citations


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, doubleblind, 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/m2/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 everolimustreated 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 everolimustreated 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, number NCT00789828;

Original languageEnglish (US)
Pages (from-to)1203-1210
Number of pages8
JournalNephrology Dialysis Transplantation
Issue number6
Publication statusPublished - 2014



  • everolimus
  • renal angiomyolipoma
  • tuberous sclerosis complex

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this