转移性或局部晚期尿路上皮癌患者的一线全身治疗：一项关于随机对照试验的系统评价和网状Meta分析
First-line systemic therapy in patients with metastatic or locally advanced urothelial carcinoma: a systematic review and network meta-analysis of randomized controlled trials.
作者信息
Xie Yandong, Liu Haoyang, Tang Yanfeng, Zhang Yaowen, Xu Nanwei, Zhao Fengnian, Zhao Jinge, Sun Guangxi, Liu Zhenhua, Shen Pengfei, Zeng Hao, Chen Junru
机构信息
Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.
Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.
出版信息
Ther Adv Med Oncol. 2025 Jul 23;17:17588359251357527. doi: 10.1177/17588359251357527. eCollection 2025.
BACKGROUND
The emergence of immune checkpoint inhibitors and antibody-drug conjugates has revolutionized the first-line treatment landscape for locally advanced or metastatic urothelial carcinoma (la/mUC). However, the optimal treatment strategy remains uncertain.
OBJECTIVES
This network meta-analysis (NMA) aimed to evaluate the efficacy and safety of various first-line treatments for la/mUC.
DESIGN
Systematic literature review with a Bayesian NMA.
DATA SOURCES AND METHODS
Eligible studies were retrieved from PubMed, EMBASE, and Web of Science, with a search cutoff of July 2024. Randomized controlled trials (RCTs) evaluating first-line treatments for la/mUC were included. Pairwise comparisons and Bayesian NMA were conducted to compare overall survival (OS) and progression-free survival (PFS) using hazard ratios (HR) and 95% credible intervals (CrIs), and objective response rate (ORR) and treatment-related adverse events (TRAEs) using odds ratios and 95% CrIs.
RESULTS
In total, 17 articles involving 11 RCTs and 7586 patients were included. Enfortumab vedotin (EV) plus pembrolizumab demonstrated the most significant improvement in OS (HR 0.47, 95% CrI 0.38-0.58) compared to platinum-based chemotherapy in the overall populations, with consistent benefits across cisplatin-eligible, cisplatin-ineligible, and PD-L1-positive/negative subgroups. EV plus pembrolizumab also ranked highest for PFS (HR 0.45, 95% CrI 0.38-0.54) and had a favorable ORR compared to other regimens. In terms of safety, atezolizumab monotherapy exhibited the lowest incidence of high-grade TRAEs, EV plus pembrolizumab had higher overall TRAE rates but lower rates of grade 3 or higher TRAEs than platinum-based chemotherapy and nivolumab plus gemcitabine-cisplatin.
CONCLUSION
This NMA provides the most comprehensive analysis of first-line treatments for la/mUC, integrating the latest clinical data. EV plus pembrolizumab demonstrated superior efficacy and acceptable safety profiles in overall and subgroup analyses, establishing it as a promising treatment option.
TRIAL REGISTRATION
The study was registered in PROSPERO (CRD42024502320).
背景
免疫检查点抑制剂和抗体药物偶联物的出现彻底改变了局部晚期或转移性尿路上皮癌（la/mUC）的一线治疗格局。然而，最佳治疗策略仍不明确。
目的
本网络荟萃分析（NMA）旨在评估la/mUC各种一线治疗的疗效和安全性。
设计
采用贝叶斯NMA的系统文献综述。
数据来源与方法
从PubMed、EMBASE和Web of Science检索符合条件的研究，检索截止日期为2024年7月。纳入评估la/mUC一线治疗的随机对照试验（RCT）。进行成对比较和贝叶斯NMA，使用风险比（HR）和95%可信区间（CrI）比较总生存期（OS）和无进展生存期（PFS），使用比值比和95% CrI比较客观缓解率（ORR）和治疗相关不良事件（TRAE）。
结果
共纳入17篇文章，涉及11项RCT和7586例患者。在总体人群中，与铂类化疗相比，恩杂鲁胺（EV）联合帕博利珠单抗在OS方面显示出最显著的改善（HR 0.47，95% CrI 0.38 - 0.58），在顺铂适用、顺铂不适用以及PD-L1阳性/阴性亚组中均有一致的获益。EV联合帕博利珠单抗在PFS方面也排名最高（HR 0.45，95% CrI 0.38 - 0.54），与其他方案相比ORR良好。在安全性方面，阿替利珠单抗单药治疗的高级别TRAE发生率最低，EV联合帕博利珠单抗的总体TRAE发生率较高，但3级或更高级别TRAE的发生率低于铂类化疗以及纳武利尤单抗联合吉西他滨 - 顺铂。
结论
本NMA整合了最新临床数据，对la/mUC的一线治疗进行了最全面的分析。EV联合帕博利珠单抗在总体和亚组分析中显示出卓越的疗效和可接受的安全性，是一种有前景的治疗选择。
试验注册
该研究已在PROSPERO注册（CRD42024502320）。
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