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Nephrol Dial Transplant. 2016 Jan;31(1):111-9. doi: 10.1093/ndt/gfv249. Epub 2015 Jul 8.

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

Author information

1
St. Jude Children's Research Hospital and Le Bonheur Children's Hospital, University of Tennessee Health Science Center, Memphis, TN, USA.
2
Royal Sussex County Hospital, Brighton, UK.
3
National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland.
4
Universitair Medisch Centrum, Utrecht, The Netherlands.
5
Minnesota Epilepsy Group, St Paul, MN, USA.
6
Moscow Research Institute of Pediatrics and Pediatric Surgery, Moscow, Russia.
7
Medizinische Klinik und Poliklinik IV, Klinikum der Universität MüNchen, Munich, Germany.
8
Osaka University Hospital, Osaka, Japan.
9
Charité Universitätsmedizin, Berlin, Germany.
10
Division of Child and Adolescent Psychiatry, University of Cape Town, Cape Town, South Africa.
11
Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
12
Novartis Pharmaceuticals S.A.S., Rueil-Malmaison, France.

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).

KEYWORDS:

everolimus; mTOR inhibitors; renal angiomyolipoma; sporadic lymphangioleiomyomatosis; tuberous sclerosis complex

PMID:
26156073
DOI:
10.1093/ndt/gfv249
[Indexed for MEDLINE]

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