Table_1_Association of Novel Androgen Receptor Axis-Targeted Therapies With Diarrhea in Patients With Prostate Cancer: A Bayesian Network Analysis.docx

ObjectiveTo perform a systematic review and network meta-analysis to characterize the effect of novel androgen receptor axis-target (ARAT) agents on diarrhea and constipation.MethodsWe searched the Pubmed, Web of Science, and ClinicalTrials.gov 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 (RR) of any-grade diarrhea and constipation for patients receiving ARAT treatment. RRs of competing treatments were evaluated by pairwise and Bayesian network meta-analysis.ResultsIn 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 (RR = 1.30, 95% CI [1.16, 1.44]). As for subgroup analysis, abiraterone, enzalutamide, and apalutamide were all associated with significant increased risk of any-grade diarrhea (abiraterone: RR = 1.40, 95% CI [1.09, 1.81]; enzalutamide: RR = 1.17, 95% CI [1.02, 1.35]; apalutamide: RR = 1.35, 95% CI [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.ConclusionThe 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).

旨在通过系统评价和网络荟萃分析，对新型雄激素受体轴靶向（ARAT）药物对腹泻和便秘的影响进行特征描述。
方法：检索至2021年9月为止的Pubmed、Web of Science和ClinicalTrials.gov数据库，寻找针对前列腺癌（CaP）患者接受新型ARAT药物治疗的3期随机对照试验（RCTs）。采用Cochrane偏倚风险工具评估试验质量。主要结局指标为接受ARAT治疗患者任何级别的腹泻和便秘的风险比（RR）。通过成对分析和贝叶斯网络荟萃分析评估竞争性治疗方案的风险比。
结果：本研究共识别出13项试验，涉及15,117名参与者，比较了5种治疗方案（阿比特龙、恩杂鲁胺、阿帕鲁胺、达鲁鲁胺和安慰剂）。新型ARAT药物的使用与任何级别腹泻显著增加的风险相关（RR = 1.30，95% CI [1.16, 1.44]）。就亚组分析而言，阿比特龙、恩杂鲁胺和阿帕鲁胺均与任何级别腹泻显著增加的风险相关（阿比特龙：RR = 1.40，95% CI [1.09, 1.81]；恩杂鲁胺：RR = 1.17，95% CI [1.02, 1.35]；阿帕鲁胺：RR = 1.35，95% CI [1.03, 1.76]）。基于贝叶斯建模，阿比特龙和恩杂鲁胺在增加任何级别腹泻风险方面具有最高和最低的排名概率。在ARAT组和对照组之间，任何级别便秘、3级或以上腹泻以及便秘的风险没有显著差异。
结论：本研究表明，新型ARAT药物的使用与腹泻显著增加的风险密切相关。在四种药物中，阿比特龙可能与转移性激素敏感性前列腺癌（mHSPC）和去势抵抗性前列腺癌（CRPC）患者中腹泻的最高风险相关。