LBA01-07 OVERALL SAFETY AND INCIDENCES OF ADVERSE EVENTS BY TIME INTERVAL WITH DAROLUTAMIDE PLUS ANDROGEN-DEPRIVATION THERAPY AND DOCETAXEL IN THE PHASE 3 ARASENS TRIAL

Abstract

You have accessJournal of UrologyCME1 May 2022LBA01-07 OVERALL SAFETY AND INCIDENCES OF ADVERSE EVENTS BY TIME INTERVAL WITH DAROLUTAMIDE PLUS ANDROGEN-DEPRIVATION THERAPY AND DOCETAXEL IN THE PHASE 3 ARASENS TRIAL E. David Crawford, Matthew R. Smith, Bertrand Tombal, Karim Fizazi, Maha Hussain, Cora N. Sternberg, Arash Rezazadeh Kalebasty, Ronald Tutrone, Neal D. Shore, Laurence Belkoff, Silke Thiele, Rui Li, Iris Kuss, Heikki Joensuu, and Fred Saad E. David CrawfordE. David Crawford More articles by this author , Matthew R. SmithMatthew R. Smith More articles by this author , Bertrand TombalBertrand Tombal More articles by this author , Karim FizaziKarim Fizazi More articles by this author , Maha HussainMaha Hussain More articles by this author , Cora N. SternbergCora N. Sternberg More articles by this author , Arash Rezazadeh KalebastyArash Rezazadeh Kalebasty More articles by this author , Ronald TutroneRonald Tutrone More articles by this author , Neal D. ShoreNeal D. Shore More articles by this author , Laurence BelkoffLaurence Belkoff More articles by this author , Silke ThieleSilke Thiele More articles by this author , Rui LiRui Li More articles by this author , Iris KussIris Kuss More articles by this author , Heikki JoensuuHeikki Joensuu More articles by this author , and Fred SaadFred Saad More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002669.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In ARASENS, darolutamide (DARO)+androgen-deprivation therapy (ADT)+docetaxel significantly reduced risk of death by 32.5% (hazard ratio [HR] 0.675; 95% confidence interval [CI] 0.568–0.801; P <0.0001) vs ADT+docetaxel in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC). We report adverse events (AEs) and their incidences by time interval from ARASENS (NCT02799602). METHODS: Pts with mHSPC were randomized 1:1 to DARO 600 mg twice daily or matching placebo (PBO)+ADT+docetaxel. AE incidences by time interval were defined as number of pts with new-onset AE or worsening AE in an interval (every 3 months for year 1; 6 months for year 2) divided by number of pts in that interval. For AEs associated with AR pathway inhibitors, exposure-adjusted incidence rates (EAIR) are presented per 100 pt years to adjust for differences in treatment duration between groups. RESULTS: Of 1306 pts randomized, safety was evaluated in 1302 pts who received DARO (652) or PBO (650). Incidences of any-grade AEs (99.5%; 98.9%), grade 3–5 AEs (70.2%; 67.5%), serious AEs (44.8%; 42.3%), and discontinuations of DARO/PBO due to AEs (13.5%; 10.6%) were comparable for both groups. The most frequently reported AEs were alopecia (40.5%; 40.6%), neutropenia (39.3%; 38.8%), and fatigue (33.1%; 32.9%); incidences in both groups were highest in the first 6 months of treatment during the docetaxel treatment period and progressively decreased thereafter (Table). Similar trends were observed for other AEs reported in >10% of pts in either treatment group, including peripheral edema, diarrhea, nausea, increased serum liver enzyme concentrations, and peripheral neuropathy. Most AEs associated with AR pathway inhibitors showed ≤2% difference between DARO and PBO. Rash (16.6%; 13.5%) and hypertension (13.7%; 9.2%) (both grouped preferred terms) occurred in more pts receiving DARO vs PBO, but EAIRs were similar between groups (rash: 6.2; 7.3; hypertension: 5.1; 5.0). CONCLUSIONS: DARO+ADT+docetaxel significantly increased overall survival without added toxicity. In general, AE incidence was similar in both groups, with the highest incidence during the first 6 months of overlapping docetaxel treatment. Source of Funding: Bayer AG and Orion Pharma © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e1038 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information E. David Crawford More articles by this author Matthew R. Smith More articles by this author Bertrand Tombal More articles by this author Karim Fizazi More articles by this author Maha Hussain More articles by this author Cora N. Sternberg More articles by this author Arash Rezazadeh Kalebasty More articles by this author Ronald Tutrone More articles by this author Neal D. Shore More articles by this author Laurence Belkoff More articles by this author Silke Thiele More articles by this author Rui Li More articles by this author Iris Kuss More articles by this author Heikki Joensuu More articles by this author Fred Saad More articles by this author Expand All Advertisement PDF DownloadLoading ...