PD34-08 ASSOCIATION BETWEEN DISEASE INDICATION AND STEROID USE AND MINERALOCORTICOID-RELATED TOXICITY OF ABIRATERONE ACETATE IN PATIENTS WITH ADVANCED PROSTATE CANCER: A META-ANALYSIS OF RANDOMIZED CONTROL TRIALS

Abstract

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) III (PD34)1 Sep 2021PD34-08 ASSOCIATION BETWEEN DISEASE INDICATION AND STEROID USE AND MINERALOCORTICOID-RELATED TOXICITY OF ABIRATERONE ACETATE IN PATIENTS WITH ADVANCED PROSTATE CANCER: A META-ANALYSIS OF RANDOMIZED CONTROL TRIALS Mary Hall, Whitney Padgett, Zachary Klaassen, Diana Magee, Aaron Laviana, Amy Luckenbaugh, Raj Satkunasivam, and Christopher Wallis Mary HallMary Hall More articles by this author , Whitney PadgettWhitney Padgett More articles by this author , Zachary KlaassenZachary Klaassen More articles by this author , Diana MageeDiana Magee More articles by this author , Aaron LavianaAaron Laviana More articles by this author , Amy LuckenbaughAmy Luckenbaugh More articles by this author , Raj SatkunasivamRaj Satkunasivam More articles by this author , and Christopher WallisChristopher Wallis More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002038.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Abiraterone acetate (AA) has proven survival benefit for patients with metastatic hormone sensitive prostate cancer (mHSPC) and metastatic castrate resistant prostate cancer (mCRPC) either before or after docetaxel chemotherapy. Due to its mechanism of action, AA requires co-administration with an oral corticosteroid. Previous randomized control trials (RCTs) have shown increased cardiac risk with AA+ androgen deprivation therapy (ADT). We compiled available evidence regarding the cardiotoxicity of AA via meta-analysis, focusing on mechanistically related side-effects and differences based on disease indication and trial design. METHODS: We performed a systematic review and meta-analysis for phase II and III RTCs of AA+ADT vs ADT for patients with prostate cancer published as of 8/11/2020. Primary outcomes were hypokalemia and fluid retention, and secondary outcomes were cardiac disorders and hypertension. We performed a meta-analysis comparing intervention and control, stratifying according to disease state (HSPC, pre-chemo mCRPC, vs post-chemo mCRPC) and trial design (steroids in the control arm). RESULTS: Among 2739 search results, 6 studies of 5,901 patients with HSPC (including mHSPC and advanced localized disease) or mCRPC were included. Treatment groups received AA 1000mg, ADT, and steroid, and controls received ADT, placebo, +/- steroid. Patients receiving AA were more likely to experience hypokalemia (17.3% vs 6.0%, p <0.001), fluid retention (24.1% vs 17.6%, p <0.001), hypertension (25.3% vs 15.1%, p <0.001), and cardiac events (25.4% vs 15.9%, p=0.002). The apparent effect of AA on these outcomes was significantly modified on the basis of whether patients in the control arm received steroid with placebo (hypokalemia: p <0.001, hypertension: p=0.01, and cardiac disorders: p <0.001) and on the basis of disease state/indication (hypokalemia: p <0.001, hypertension: p=0.03, and cardiac disorders: p=0.01). CONCLUSIONS: The magnitude of cardiovascular effects attributable to AA vary significantly by trial design and disease indication; studies in which steroids were not given to the control group demonstrate an increased attributable risk while patients receiving AA earlier in the disease process appear to have a greater magnitude of risk of several adverse events, including hypokalemia and hypertension. These hypothesis-generating data may be helpful in understanding AA toxicity and offering individualized counseling. Source of Funding: none © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e585-e586 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mary Hall More articles by this author Whitney Padgett More articles by this author Zachary Klaassen More articles by this author Diana Magee More articles by this author Aaron Laviana More articles by this author Amy Luckenbaugh More articles by this author Raj Satkunasivam More articles by this author Christopher Wallis More articles by this author Expand All Advertisement Loading ...