Prostate Cancer Therapy Cardiotoxicity Map (PROXMAP) for Advanced Disease States: A Systematic Review and Network Meta-analysis with Bayesian Modeling of Treatment Histories

IF 25.3 1区医学 Q1 UROLOGY & NEPHROLOGY

European urology Pub Date : 2025-01-01 DOI:10.1016/j.eururo.2024.08.031

Moez Karim Aziz , Donald Molony , Dominique Monlezun , Travis Holder , Oliver Brunckhorst , Noel Higgason , Jerry Roland , Resa Magill , Mariya Fatakdawala , Alexander Iacobucci , Neal Mody-Bailey , Chris Owen , Andrew Zarker , Emma Thames , Justin Swaby , Daniel Xiao , Lily Choi , Shubh Desai , Jacob Galan , Brett Deng , Steven Canfield

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引用次数: 0

Abstract

Background and objective

Recommendations of first-line therapies for metastatic hormone-sensitive (mHSPC), nonmetastatic castrate-resistant (M0CRPC), and metastatic castrate-resistant (mCRPC) prostate cancer do not account for cardiotoxicity due to a lack of clear prior evidence. This manuscript assesses cardiotoxicity of these therapies.

Methods

We searched Ovid Medline, Elsevier Embase, and the Cochrane Library for randomized clinical trials (RCTs) from database inception to January 14, 2024. Network meta-analyses of first-line mHSPC, M0CRPC, and mCRPC therapies were constructed for the five cardiotoxicity metrics defined by the International Cardio-Oncology Society: heart failure, myocarditis, vascular toxicity, hypertension, and arrhythmias. Additional Bayesian network meta-analyses also accounted for prior treatment history.

Key findings and limitations

Thirteen RCTs (16 292 patients) were included. For mHSPC, androgen deprivation therapy (ADT) plus docetaxel (DTX) plus abiraterone acetate (AA) with prednisone (P) demonstrated a significant increase in hypertension and arrhythmias versus ADT + DTX (risk ratio [RR] 2.85, 95% confidence interval [CI] 1.67–4.89, and RR 2.01, 95% CI 1.17–3.44, respectively); however, no corresponding differences were observed between ADT + DTX plus darolutamide (DAR) and ADT + DTX (RR 1.55, 95% CI 0.73–3.30, and RR 0.94, 95% CI 0.63–1.40, respectively). For mCRPC assuming a history of mHSPC treatment, ADT + AA + P plus olaparib (OLA) demonstrated a statistically significant decrease in hypertension versus ADT + AA + P (RR 0.20, 95% CI 0.16–0.26). M0CRPC results were unremarkable.

Conclusions and clinical implications

For mHSPC, ADT + DTX + DAR demonstrates less cardiotoxicity than ADT + DTX + AA + P due to a lower risk of hypertension and arrhythmias from decreased mineralocorticoid excess. In addition, OLA counterintuitively offers decreased hypertension when superimposed on ADT + AA + P for mCRPC treatment after prior androgen deprivation from mHSPC therapy.

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针对晚期疾病状态的前列腺癌治疗心脏毒性图谱（PROXMAP）：采用贝叶斯治疗历史建模的系统综述和网络 Meta 分析。

背景和目的：由于缺乏明确的前期证据，针对转移性激素敏感型（mHSPC）、非转移性阉割耐药型（M0CRPC）和转移性阉割耐药型（mCRPC）前列腺癌的一线疗法建议并未考虑心脏毒性。本稿件评估了这些疗法的心脏毒性：我们检索了 Ovid Medline、Elsevier Embase 和 Cochrane 图书馆中从数据库开始到 2024 年 1 月 14 日的随机临床试验 (RCT)。根据国际心脏肿瘤学会定义的五项心脏毒性指标：心力衰竭、心肌炎、血管毒性、高血压和心律失常，对一线mHSPC、M0CRPC和mCRPC疗法进行了网络荟萃分析。其他贝叶斯网络荟萃分析也考虑了先前的治疗史：共纳入13项RCT（16292名患者）。对于 mHSPC，雄激素剥夺疗法（ADT）加多西他赛（DTX）加醋酸阿比特龙（AA）加泼尼松（P）与 ADT + DTX 相比，高血压和心律失常的发生率显著增加（风险比 [RR] 2.85，95% 置信区间 [CI] 1.67-4.89，和 RR 2.01，95% CI 1.17-3.44，分别）；然而，在 ADT + DTX 加达罗他胺（DAR）和 ADT + DTX 之间未观察到相应差异（RR 1.55，95% CI 0.73-3.30，和 RR 0.94，95% CI 0.63-1.40，分别）。对于假定有mHSPC治疗史的mCRPC，ADT + AA + P加奥拉帕利（OLA）与ADT + AA + P相比，高血压的下降具有统计学意义（RR为0.20，95% CI为0.16-0.26）。M0CRPC结果无显著差异：对于mHSPC，ADT + DTX + DAR的心脏毒性低于ADT + DTX + AA + P，这是因为矿物质皮质激素过量降低了高血压和心律失常的风险。此外，在使用 ADT + AA + P 治疗 mCRPC 时，如果事先对 mHSPC 治疗进行了雄激素剥夺，在叠加 ADT + AA + P 治疗后，OLA 会反直觉地降低高血压。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European urology 医学-泌尿学与肾脏学

CiteScore

43.00

自引率

2.60%

发文量

1753

审稿时长

23 days

期刊介绍： European Urology is a peer-reviewed journal that publishes original articles and reviews on a broad spectrum of urological issues. Covering topics such as oncology, impotence, infertility, pediatrics, lithiasis and endourology, the journal also highlights recent advances in techniques, instrumentation, surgery, and pediatric urology. This comprehensive approach provides readers with an in-depth guide to international developments in urology.