AUTHOR=Xiong Xingyu , Xu Hang , Wang Sheng , Liao Xinyang , Yi Xianyanling , Jin Kun , Lei Haoran , Bai Shengjiang , Qiu Shi , Yang Lu 

TITLE=Association of Novel Androgen Receptor Axis-Targeted Therapies With Diarrhea in Patients With Prostate Cancer: A Bayesian Network Analysis

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2022

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.800823

DOI=10.3389/fmed.2021.800823

ISSN=2296-858X

ABSTRACT=<sec><title>Objective</title><p>To perform a systematic review and network meta-analysis to characterize the effect of novel androgen receptor axis-target (ARAT) agents on diarrhea and constipation.</p></sec><sec><title>Methods</title><p>We searched the Pubmed, Web of Science, and <ext-link ext-link-type="uri" xlink:href="https://ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials.gov</ext-link> up to September 2021 for phase 3 randomized controlled trials (RCTs) of patients receiving novel ARAT agents for prostate cancer (CaP). A Cochrane risk-of-bias tool was used to assess trial quality. The primary outcomes were risk ratio (<italic>RR</italic>) of any-grade diarrhea and constipation for patients receiving ARAT treatment. <italic>RR</italic>s of competing treatments were evaluated by pairwise and Bayesian network meta-analysis.</p></sec><sec><title>Results</title><p>In this study, 13 trials with 15,117 participants comparing 5 treatments (abiraterone, enzalutamide, apalutamide, darolutamide, and placebo) were identified. Use of novel ARAT agents was associated with a significant increased risk of any-grade diarrhea (<italic>RR</italic> = 1.30, 95% <italic>CI</italic> [1.16, 1.44]). As for subgroup analysis, abiraterone, enzalutamide, and apalutamide were all associated with significant increased risk of any-grade diarrhea (abiraterone: <italic>RR</italic> = 1.40, 95% <italic>CI</italic> [1.09, 1.81]; enzalutamide: <italic>RR</italic> = 1.17, 95% <italic>CI</italic> [1.02, 1.35]; apalutamide: RR = 1.35, 95% <italic>CI</italic> [1.03, 1.76]). Based on Bayesian modeling, abiraterone and enzalutamide showed the highest and lowest probability to rank first in terms of increasing risk of any-grade diarrhea. There were no significant differences of risk in any-grade constipation, grade 3 or greater diarrhea, and constipation between ARAT and control group.</p></sec><sec><title>Conclusion</title><p>The present study indicates that the use of novel ARAT agents is associated with a significantly higher risk of diarrhea. Across the four agents, abiraterone may relate to the highest risk of diarrhea among patients with metastatic hormone sensitive prostate cancer (mHSPC) and castration-resistant prostate cancer (CRPC).</p></sec>