PD35-10 EVEROLIMUS FOR RENAL ANGIOMYOLIPOMA ASSOCIATED WITH TUBEROUS SCLEROSIS COMPLEX: EFFICACY AND SAFETY AFTER 3.5 YEARS OF TREATMENT IN THE EXIST-2 STUDY

Abstract

You have accessJournal of UrologyKidney Cancer: Advanced I1 Apr 2015PD35-10 EVEROLIMUS FOR RENAL ANGIOMYOLIPOMA ASSOCIATED WITH TUBEROUS SCLEROSIS COMPLEX: EFFICACY AND SAFETY AFTER 3.5 YEARS OF TREATMENT IN THE EXIST-2 STUDY John Bissler, J. Kingswood, Elzbieta Radzikowska, Bernard Zonnenberg, Michael Frost, Elena Belousova, Matthias Sauter, Norio Nonomura, Susanne Brakemeier, Petrus de Vries, Noah Berkowitz, Severine Peyrard, and Klemens Budde John BisslerJohn Bissler More articles by this author , J. KingswoodJ. Kingswood More articles by this author , Elzbieta RadzikowskaElzbieta Radzikowska More articles by this author , Bernard ZonnenbergBernard Zonnenberg More articles by this author , Michael FrostMichael Frost More articles by this author , Elena BelousovaElena Belousova 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 de VriesPetrus de Vries More articles by this author , Noah BerkowitzNoah Berkowitz More articles by this author , Severine PeyrardSeverine Peyrard More articles by this author , and Klemens BuddeKlemens Budde More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2233AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES EXIST-2 (NCT00790400), a randomized, double-blind, phase 3 trial, assessed everolimus, an oral mammalian target of rapamycin (mTOR) inhibitor, for the treatment of renal angiomyolipoma associated with either tuberous sclerosis complex (TSC) or sporadic lymphangioleiomyomatosis (sLAM). Here we present longer-term safety and efficacy data for everolimus that include the open-label extension phase (cutoff date, April 1, 2014). METHODS 118 patients who had renal angiomyolipoma associated with TSC (n=113) or sLAM (n=5) were randomly assigned 2:1 to receive 10 mg/day everolimus (n=79) or placebo (n=39). Angiomyolipoma response rate, the primary endpoint, was defined as the proportion of patients with confirmed ≥50% reduction in sum of volumes of all target angiomyolipoma relative to baseline in the absence of an increase in kidney volume (>20% from nadir), no new angiomyolipoma lesions, and no angiomyolipoma-related bleeding of ≥ grade 2. Adverse events (AEs) were monitored at each visit. RESULTS At the initial cutoff (June 30, 2011), everolimus was superior to placebo for angiomyolipoma response rate (42% vs 0%, P<0.0001). Following these positive results, all patients still in the study were offered open-label everolimus in the extension phase. As of April 1, 2014, 112 patients (median age, 32 years [range 18-62]) received ≥1 dose of everolimus. Median duration of exposure was 39.8 months (range, 0.5-57.3). Angiomyolipoma response rate was 56.3% (95% confidence interval [CI], 46.6%-65.6%). At week 96 (n=98), 80.6% and 63.3% of patients had reductions ≥30% and ≥50%, respectively, in angiomyolipoma volume. Progression-free rate at 48 months was 78.3% (95% CI, 63.6%-87.6%). AEs were similar to previous reports and remained mostly grade 1 or 2. AEs most commonly reported in ≥20% of patients were nasopharyngitis (44.6%), stomatitis (42.9%), hypercholesterolemia (35.7%), acne and headache (31.3% each), urinary tract infection (30.4%), aphthous stomatitis (25.9%), diarrhea (24.1%), hypertension (23.2%), cough (21.4%), and nausea (20.5%). Incidence of emerging AEs decreased over the study period. The most frequent grade 3 AEs (≥3%) were blood phosphorus decreased (4.5%) and amenorrhea (5.6%, n=4 out of 71 females aged 10-55). The only grade 4 event occurring in ≥2 patients was blood uric acid increased (2.7%). CONCLUSIONS A sustained reduction in angiomyolipoma volume was seen with continued everolimus treatment. No new safety concerns were noted. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e763 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information John Bissler More articles by this author J. Kingswood More articles by this author Elzbieta Radzikowska More articles by this author Bernard Zonnenberg More articles by this author Michael Frost More articles by this author Elena Belousova 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 de Vries More articles by this author Noah Berkowitz More articles by this author Severine Peyrard More articles by this author Klemens Budde More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...