AMSTERDAM—Everolimus appears to dramatically shrink renal angiomyolipomas in pediatric patients with tuberous sclerosis complex (TSC)-associated subependymal giant cell astrocytoma (SEGA), researchers reported at the 51st Congress of the European Renal Association-European Dialysis and Transplant Association.

“Everolimus, which is an oral inhibitor of the mammalian target of rapamycin, is not yet licensed for the treatment of renal angiomyolipomas in children although it is approved for treatment in adults,” J. Chris Kingswood, FCRP, Consultant in the Sussex Kidney Unit at the Royal Sussex County Hospital in Brighton, UK, pointed out.  “However, the effect in children is very exciting. We have found that the treatment is very effective and thus far has shown a low frequency of side effects.”

Dr. Kingswood and his colleagues examined the effect of everolimus on angiomyolipoma growth in TSC patients being treated for SEGA who were younger than 18 years at the start of everolimus treatment in the EXIST-1 trial. Everolimus is approved to treat SEGA, a brain tumor also associated with TSC.

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The phase 3 EXIST-1 (EXamining everolimus In a Study of Tuberous Sclerosis Complex-1) study found that everolimus was superior to placebo for the primary endpoint of reduction in SEGA volume (35% vs. 0%).

A predefined exploratory endpoint of the trial was the renal angiomyolipoma response rate in the subset of patients with 1 or more target angiomyolipoma lesions at baseline. All measurable angiomyolipomas with the longest diameter of at least 1.0 cm) were identified as target lesions.

Angiomyolipoma response was defined as a 50% reduction in the sum of volumes of all target lesions relative to baseline;  no new lesions 1 cm or more in longest diameter;  no increase in kidney volume of 20% or more from the lowest value obtained for the patient; and no angiomyolipoma-related bleeding of grade 2 or more.

In 33 pediatric patients who received open-label everolimus in an extension phase of the EXIST-1 study, the angiomyolipoma response rate was 71.9% after 96 weeks of treatment.  

A single grade 1 event of hematuria occurred.  Adverse events that were significantly more common in the everolimus than placebo arm in the overall trial included mouth ulcers and stomatitis.

Renal angiomyolipomas have been reported in up to 75% of patients with the genetic disorder TSC, Dr. Kingswood observed.  Lesions are usually multiple, bilateral, and progressive.  In addition, the risk of spontaneous life-threatening hemorrhage is increased as angiomyolipomas enlarge. Lesions tend to re-grow after surgery, which is the conventional treatment for renal angiomyolipomas.

Approximately 40% of people with TSC will “run into serious trouble” as adults due to renal complications, he noted.  For example, his own team has found that the likelihood of having chronic kidney disease prior to the age of 65 is more than 5 times greater in patients with TSC than in the general U.K. population.

“The main goal in the treatment of TSC-associated renal angiomyolipomas is to prevent their enlargement, thus decreasing the risk of future bleeding and chronic kidney disease,” Dr. Kingswood said. “Our results suggest that we may be able to achieve this goal with preventive drug therapy.”