Journal WatchCommentary on: Everolimus for Angiomyolipoma Associated With Tuberous Sclerosis Complex or Sporadic Lymphangioleiomyomatosis (EXIST-2): A Multicentre, Randomised, Double-blind, Placebo-controlled Trial
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Summary
This was a double-blind, phase III trial comparing everolimus (10 mg) to placebo in patients with at least 1 angiomyolipoma (AML) measuring ≥3 cm and a definite diagnosis of tuberous sclerosis (TS) or sporadic lymphangioleiomyomatosis. The primary efficacy endpoint was the proportion of patients with ≥50% reduction in total volume of the target AML relative to baseline. The study drug was given in all cases until AML progression, the occurrence of unacceptable adverse effects, or patient
Comment
AML are common in patients with TS and are the most frequent cause of death in adult patients with this disease. This trial is an excellent example of elucidation of the molecular mechanisms of a disease leading to specific, targeted therapy. In TS, the underlying mutations in the “tuberous sclerosis complex” lead to activation of the mammalian target of rapamycin (mTOR) pathway. Targeting mTOR with specific inhibitors is, therefore, a rational approach to treating patients with TS. Multiple
References (4)
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Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial
Lancet
(2013) - et al.
Multicenter phase 2 trial of sirolimus for tuberous sclerosis: kidney angiomyolipomas and other tumors regress and VEGF-D levels decrease
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Cited by (0)
John J. Bissler, J. Christopher Kingswood, Elżbieta Radzikowska, et al.
Lancet Oncol Epub 2013 http://dx.doi.org/10.1016/S0140-6736(12)61767-X 1.