Everolimus for the Treatment of Angiomyolipoma in Patients with Tuberous Sclerosis Complex or Sporadic Lymphangioleiomyomatosis: Results from EXIST-2 (P04.188)

Objective: To examine everolimus, an oral mTOR inhibitor, for treating angiomyolipoma (AML) associated with tuberous sclerosis complex (TSC) or sporadic lymphangioleiomyomatosis (sLAM). Background TSC is an autosomal dominant genetic disorder associated with tumor growth in the brain, kidney, lung, and heart. Lesions within the kidney, AMLs, are also associated with the rare pulmonary disorder sLAM. Design/Methods: EXIST-2 (NCT00790400) is a prospective, randomized, double-blind, placebo-controlled, phase 3 study. Patients (≥1 AML with longest diameter ≥3cm) were randomized 2:1 to receive 10 mg/day everolimus (n=79) or placebo (n=39) and stratified by TSC and enzyme-inducing anti-epileptic drug (EIAED) use or non-use, and sLAM. The primary efficacy endpoint, proportion of patients with AML response (best overall confirmed ≥50% reduction in sum of volumes of all target AML relative to baseline), was assessed by central review of kidney CT/MRI (baseline, 12, 24, 48 weeks, and then annually). Secondary efficacy endpoints included time to AML progression and skin lesion response rate (complete or partial response in patients ≥1 skin lesion at baseline [n=114]). Adverse events (AEs) were monitored at each visit. Results: Patient characteristics were balanced across groups. Median treatment duration of everolimus and placebo was 38.1 and 34.0 weeks, respectively. Everolimus best overall AML response rate was superior to placebo (41.8% vs 0%; P Conclusions: Everolimus produced statistically significantly superior results in best overall AML response rate, increased time to AML progression, and best overall skin lesion response rate compared with placebo. Supported by: Novartis. Disclosure: Dr. Frost has nothing to disclose. Dr. Budde has nothing to disclose. Dr. Kingswood has received personal compensation for activities with Novartis and Otsaku as an advisor and investigator. Dr. Kingswood has received compensation for serving on the Board of Tourette Syndrome Association. Dr. Zonnenberg has nothing to disclose. Dr. Belousova has nothing to disclose. Dr. Radzikowska has nothing to disclose. Dr. Sauter has nothing to disclose. Dr. Nonomura has nothing to disclose. Dr. Brakemeier has nothing to disclose. Dr. de Vries has nothing to disclose. Dr. Sahmoud has received personal compensation for activities Novartis as an employee. Dr. Sahmoud holds stock and/or stock options in Novartis. Dr. Shah has received personal compensation for activities with Novartis as an employee. Dr. Miao has received personal compensation for activities with Novartis as an employee. Dr. Gray has received personal compensation for activities with Novartis as an employee. Dr. Bissler has received personal compensation for activities with Novartis, Patents and Inventions British Technology Group, Scientific Advisor or Membership LAM Foundation, TS Alliance, Kidney Foundation of Greater Cincinnati. Dr. Bissler has received research support from Novartis.