Abstract 13534: A Systematic Review and Network Meta-Analysis of Non-Metastatic Castrate Resistant Prostate Cancer Therapy Cardiotoxicity

Abstract

Introduction: For non-metastatic castrate resistant prostate cancer (M0CRPC) with a prostate-specific antigen doubling time of < 10 months, European Association of Urology (EAU) guidelines recommend androgen deprivation therapy (ADT) plus either enzalutamide, apalutamide, or darolutamide as first-line therapy. However, this recommendation does not account for potential cardiotoxicity of treatments. Hypothesis: We expect differences among first-line therapies for the five International Cardio-Oncology Society (IC-OS) cardiotoxicity domains: heart failure, myocarditis, vascular toxicity, hypertension, and arrhythmias. Methods: We searched Ovid Medline, Elsevier Embase, and the Cochrane Library for randomized clinical trials (RCTs) from inception until August 2022. Studies with clearly stratified M0CRPC reporting at least one first-line therapy and cardiotoxicity domain were included. RCTs were grouped into mid- (< 24 months) and long-term (> 24 months) studies based on median duration of follow-up. Frequentist fixed-effect network meta-analysis was performed to estimate risk ratio (RR) and 95% confidence intervals (CI). Results: For hypertension and vascular toxicity, 3 mid- and 3 long-term studies were found. Two mid- and 3 long-term studies assessed arrhythmias. For heart failure, 2 mid- and 2 long-term studies were found. All studies had a similar placebo population treated with ADT alone. Median follow-up times for mid- and long-term studies are shown in Figure 1. We did not find any RCTs assessing myocarditis. However, compared to other first line therapies, ADT plus enzalutamide was associated with increased risk of hypertension in the mid- and long-term. Increased risk of vascular toxicity was also detected but only in the long-term (Figure 1). Conclusions: Enzalutamide is associated with higher risk of cardiotoxicity compared to other first-line androgen receptor targeted antagonists.