Everolimus for renal angiomyolipoma in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis: extension of a randomized controlled trial.

Abstract

BACKGROUND:

Mammalian target of rapamycin (mTOR) inhibitors are recommended as first-line treatment of renal angiomyolipoma associated with tuberous sclerosis complex (TSC) or sporadic lymphangioleiomyomatosis (sporadic LAM), but follow-up is limited. Longer term efficacy and tolerability data from a Phase 3, double-blind, placebo-controlled trial are presented.

METHODS:

Following favorable results from the primary analysis (data cutoff 30 June 2011) of the EXIST-2 trial, patients still receiving study treatment were allowed to enter an open-label extension. Everolimus was initiated at 10 mg once daily and titrated based on tolerability. The primary outcome was angiomyolipoma response rate (≥ 50% reduction from baseline in target lesion volumes). Safety was a secondary endpoint.

RESULTS:

As of the cutoff date (1 May 2013), 112 patients had received everolimus, and the response rate in 107 patients with angiomyolipoma (median duration of medication exposure of 28.9 months) was 54%. The proportion of patients achieving angiomyolipoma reductions of ≥ 30% and ≥ 50% increased over time, reaching 81.6% (62/76) and 64.5% (49/76), respectively, by Week 96. No everolimus-treated patients experienced renal bleeding. The long-term safety profile was consistent with previous reports; adverse events (AEs) were mostly Grade 1/2, and there were no new safety issues. The frequency of emerging AEs and severe AEs lessened over time.

CONCLUSIONS:

Longer term everolimus treatment appeared safe and effective in patients with TSC- or sporadic LAM-associated renal angiomyolipoma not requiring surgical intervention. Continued reduction in angiomyolipoma volume was demonstrated, and there was no angiomyolipoma-related bleeding; AEs were predictable and generally manageable.

TRIAL REGISTRATION:

clinicaltrialsgov identifier: NCT00790400 (http://clinicaltrials.gov/ct2/show/NCT00790400).

• Authors: John J Bissler, John Christopher Kingswood, Elżbieta Radzikowska, Bernard A Zonnenberg, Michael Frost, Elena Belousova, Matthias Sauter, Norio Nonomura, Susanne Brakemeier, Petrus J de Vries, Noah Berkowitz, Sara Miao, Scott Segal, Severine Peyrard, Klemens Budde
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 31 Issue 1 Pg. 111-9 (Jan 2016) ISSN: 1460-2385 [Electronic] England
• PMID: 26156073 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Chemical References

• Antineoplastic Agents
• Everolimus

Topics

• Adolescent
• Adult
• Angiomyolipoma (drug therapy, pathology)
• Antineoplastic Agents (therapeutic use)
• Disease-Free Survival
• Double-Blind Method
• Everolimus (therapeutic use)
• Female
• Humans
• Kaplan-Meier Estimate
• Kidney (pathology)
• Kidney Neoplasms (drug therapy, pathology)
• Lymphangioleiomyomatosis (drug therapy)
• Male
• Middle Aged
• Treatment Outcome
• Tuberous Sclerosis (drug therapy)
• Tumor Burden (drug effects)
• Young Adult