PD44-02 PHARMACOGENOMIC DETERMINANTS OF SERUM STEROID HORMONE RESPONSES TO ABIRATERONE OR ENZALUTAMIDE AND HSD3B1 GENE MUTATION IN CRPC PATIENTS

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology II (PD44)1 Sep 2021PD44-02 PHARMACOGENOMIC DETERMINANTS OF SERUM STEROID HORMONE RESPONSES TO ABIRATERONE OR ENZALUTAMIDE AND HSD3B1 GENE MUTATION IN CRPC PATIENTS Hosam Serag, Emilia Chen, Hans Adomat, Daniel Khalaf, Alexander Wyatt, and Martin Gleave Hosam SeragHosam Serag More articles by this author , Emilia ChenEmilia Chen More articles by this author , Hans AdomatHans Adomat More articles by this author , Daniel KhalafDaniel Khalaf More articles by this author , Alexander WyattAlexander Wyatt More articles by this author , and Martin GleaveMartin Gleave More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002058.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Abiraterone and enzalutamide are commonly used for treating patients with castration-resistant prostate cancer (CRPC). Serum levels of steroid hormones can be affected by drug type and mutation in the gene HSD3B1, with potential implications for outcome prediction. Objective: To determine the impact of treatment with abiraterone or enzalutamide as well as HSD3B1 gene mutation on steroid hormones, quantified by mass spectrometry (MS) in patients with CRPC. METHODS: A multicentre, randomised, crossover trial was performed in six cancer centres in British Columbia, Canada. Adult patients with metastatic CRPC were included. In this study we performed retrospective steroid MS analysis from patients in both arms of the trial.Patients were randomly assigned to groups A and B (1:1). Group A received Abiraterone acetate until PSA progression, followed by crossover to Enzalutamide. Group B followed the opposite sequence. Primary outcomes included levels of testosterone (T), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), androstenedione, and progesterone at baseline, before crossover, and at the end of therapy (EOT) as well as variants of HSD3B1 allele. RESULTS: Baseline serum levels of T, DHT, DHEA, androstenedione, and progesterone were similar between the two arms. On crossover, the levels of T, DHT, DHEA, and androstenedione significantly decreased, while progesterone level significantly increased, in the abiraterone arm compared to the enzalutamide arm. This is reversed after patient cross-over (Figure 1). No significant association was detected in the levels of steroid hormones between HSD3B1 (1245 A) and HSD3B1 (1245 A>C) genotypes either at baseline, or after exposure to either treatment (Figure 2). The sample size was relatively small for assessing effect of HSD3B1 mutations. CONCLUSIONS: The results confirm expected effects of abiraterone and enzalutamide on steroid hormones levels in CRPC patients. HSD3B1 mutation seems not to affect levels of steroid hormones. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e736-e737 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hosam Serag More articles by this author Emilia Chen More articles by this author Hans Adomat More articles by this author Daniel Khalaf More articles by this author Alexander Wyatt More articles by this author Martin Gleave More articles by this author Expand All Advertisement Loading ...