PD17-01 EVEROLIMUS FOR RENAL ANGIOMYOLIPOMA ASSOCIATED WITH TUBEROUS SCLEROSIS COMPLEX: EXIST-2 LONG-TERM EFFICACY AND SAFETY

Abstract

You have accessJournal of UrologyKidney Cancer: Localized II1 Apr 2014PD17-01 EVEROLIMUS FOR RENAL ANGIOMYOLIPOMA ASSOCIATED WITH TUBEROUS SCLEROSIS COMPLEX: EXIST-2 LONG-TERM EFFICACY AND SAFETY John Bissler, J. Christopher Kingswood, Elzbieta Radzikowska, Bernard A. Zonnenberg, Michael Frost, Matthias Sauter, Norio Nonomura, Susanne Brakemeier, Petrus J. de Vries, Scott Segal, Oezlem Anak, Severine Peyard, and Klemens Budde John BisslerJohn Bissler More articles by this author , J. Christopher KingswoodJ. Christopher Kingswood More articles by this author , Elzbieta RadzikowskaElzbieta Radzikowska More articles by this author , Bernard A. ZonnenbergBernard A. Zonnenberg More articles by this author , Michael FrostMichael Frost More articles by this author , Matthias SauterMatthias Sauter More articles by this author , Norio NonomuraNorio Nonomura More articles by this author , Susanne BrakemeierSusanne Brakemeier More articles by this author , Petrus J. de VriesPetrus J. de Vries More articles by this author , Scott SegalScott Segal More articles by this author , Oezlem AnakOezlem Anak More articles by this author , Severine PeyardSeverine Peyard More articles by this author , and Klemens BuddeKlemens Budde More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1508AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives To assess the long-term efficacy and safety of everolimus, an oral mTOR inhibitor, for the treatment of renal angiomyolipoma associated with either tuberous sclerosis complex (TSC) or sporadic lymphangioleiomyomatosis (LAM). Methods EXIST-2 (NCT00790400), a randomized, double-blind, phase 3 trial, assessed the efficacy and safety of everolimus for the treatment of renal angiomyolipoma associated with either TSC or sporadic LAM. A total of 118 patients (median age, 31 years [range, 18-61]) who had renal angiomyolipoma associated with TSC (n=113) or sporadic LAM (n=5) were randomly assigned (2:1) to 10 mg/day everolimus (n=79) or placebo (n=39). Angiomyolipoma response rate (primary end point) was defined as the proportion of patients with confirmed ≥50% reduction in the sum of volumes of all target angiomyolipoma relative to baseline in the absence of kidney increase (>20% from nadir), no new angiomyolipoma lesions, and no angiomyolipoma-related bleeding of ≥ grade 2. Adverse events (AEs) were monitored at every visit. Results Everolimus was superior to placebo for the primary end point, renal angiomyolipoma response rate (42% vs 0%; P<0.0001; original data cutoff, 6/30/2011). Following positive results for the original cutoff, placebo patients were offered open-label everolimus in the study extension phase. As of 5/1/2013, 112 patients received ≥1 dose of everolimus, and the median duration of exposure was 29 months (range, 0.5-46). The angiomyolipoma response rate was 54% (95% confidence interval, 44-63). AEs were similar to those at the original cutoff and continued to be grade 1 or 2. The most frequent grade 3 AEs were blood phosphorus decreased (4%) and amenorrhea (3%). Individual grade 4 AEs occurred in <2% of patients; they were blood uric acid increase (n=2), convulsion, hydrocephalus, hypertensive crisis, neutropenia, pancreatic carcinoma, and rhabdomyolysis (n=1 each). The most common AEs reported in ≥20% of patients were nasopharyngitis and stomatitis (43% each), headache, acne and hypercholesterolemia (30% each), urinary tract infection (28%), aphthous stomatitis (26%), and cough (21%). Hemorrhages were seen in 34 patients (30%), with the most frequently (≥5%) reported AEs being epistaxis (10%), menorrhagia (8%), and vaginal hemorrhage unrelated to normal menstruation (7%). Of note, there were no renal hemorrhages in patients taking everolimus. Conclusions Everolimus continued to reduce angiomyolipoma volume with no new safety concerns. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e540 Advertisement Copyright & Permissions© 2014MetricsAuthor Information John Bissler More articles by this author J. Christopher Kingswood More articles by this author Elzbieta Radzikowska More articles by this author Bernard A. Zonnenberg More articles by this author Michael Frost More articles by this author Matthias Sauter More articles by this author Norio Nonomura More articles by this author Susanne Brakemeier More articles by this author Petrus J. de Vries More articles by this author Scott Segal More articles by this author Oezlem Anak More articles by this author Severine Peyard More articles by this author Klemens Budde More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...