Adjuvant Immunotherapy in High-Risk Muscle-Invasive Urothelial Cancer: An Updated Meta-Analysis of Randomized Controlled Trials.

Clinical genitourinary cancer Pub Date : 2025-02-01 Epub Date: 2024-12-04 DOI:10.1016/j.clgc.2024.102288
Isadora Mamede, Caroliny Silva, Ana Caroline Alves, Joao Pedro Oliveira, Melissa Maia, Caio Dabbous de Liz, Audrey Cabral de Oliveira
{"title":"Adjuvant Immunotherapy in High-Risk Muscle-Invasive Urothelial Cancer: An Updated Meta-Analysis of Randomized Controlled Trials.","authors":"Isadora Mamede, Caroliny Silva, Ana Caroline Alves, Joao Pedro Oliveira, Melissa Maia, Caio Dabbous de Liz, Audrey Cabral de Oliveira","doi":"10.1016/j.clgc.2024.102288","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Neoadjuvant cisplatin-based chemotherapy followed by radical surgery is the standard treatment for muscle-invasive urothelial carcinoma (MIUC). The Checkmate-274 and AMBASSADOR trials have demonstrated improvements in disease-free survival (DFS) with adjuvant immunotherapy. Consequently, this meta-analysis aimed to assess the effectiveness of strategies involving checkpoint inhibitors in managing high-risk MIUC.</p><p><strong>Patients and methods: </strong>We searched PubMed, Embase, Cochrane, ClinicalTrials.gov, EAU24, and ASCO GU abstracts for randomized controlled trials (RCTs) comparing adjuvant PD-1 and PD-L1 inhibitors against control (placebo or observation) for MIUC. Outcomes included DFS, grade ≥3 adverse events (AEs), and overall survival (OS). Heterogeneity was assessed using I2 statistics, employing a random-effects model for analysis.</p><p><strong>Results: </strong>In a cohort of 2220 patients from three RCTs, 1,113 (50.14%) underwent adjuvant immunotherapy. This treatment significantly increased DFS (HR 0.76; 95% CI, 0.65-0.90; P < .01), particularly in lower tract tumors (HR 0.71; 95% CI, 0.56-0.91; P < .01). No substantial DFS improvement surfaced in the upper tract subgroup (P = .28) (p-interaction = .01). PD-L1 status (p-interaction = .83) and previous neoadjuvant chemotherapy (p-interaction = .11) did not significantly affect outcomes. However, immunotherapy correlated with higher grade ≥3 AEs (RR 1.47; P < .01), with no notable difference in OS (P = .07).</p><p><strong>Conclusions: </strong>Adjuvant PD-1/PD-L1 inhibitors notably enhance MIUC DFS, particularly in lower tract tumors, regardless of PD-L1 status. These findings support immunotherapy, especially anti-PD1, as a valuable adjuvant treatment strategy for high-risk MIUC patients.</p>","PeriodicalId":93941,"journal":{"name":"Clinical genitourinary cancer","volume":"23 1","pages":"102288"},"PeriodicalIF":0.0000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical genitourinary cancer","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.clgc.2024.102288","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/4 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Introduction: Neoadjuvant cisplatin-based chemotherapy followed by radical surgery is the standard treatment for muscle-invasive urothelial carcinoma (MIUC). The Checkmate-274 and AMBASSADOR trials have demonstrated improvements in disease-free survival (DFS) with adjuvant immunotherapy. Consequently, this meta-analysis aimed to assess the effectiveness of strategies involving checkpoint inhibitors in managing high-risk MIUC.

Patients and methods: We searched PubMed, Embase, Cochrane, ClinicalTrials.gov, EAU24, and ASCO GU abstracts for randomized controlled trials (RCTs) comparing adjuvant PD-1 and PD-L1 inhibitors against control (placebo or observation) for MIUC. Outcomes included DFS, grade ≥3 adverse events (AEs), and overall survival (OS). Heterogeneity was assessed using I2 statistics, employing a random-effects model for analysis.

Results: In a cohort of 2220 patients from three RCTs, 1,113 (50.14%) underwent adjuvant immunotherapy. This treatment significantly increased DFS (HR 0.76; 95% CI, 0.65-0.90; P < .01), particularly in lower tract tumors (HR 0.71; 95% CI, 0.56-0.91; P < .01). No substantial DFS improvement surfaced in the upper tract subgroup (P = .28) (p-interaction = .01). PD-L1 status (p-interaction = .83) and previous neoadjuvant chemotherapy (p-interaction = .11) did not significantly affect outcomes. However, immunotherapy correlated with higher grade ≥3 AEs (RR 1.47; P < .01), with no notable difference in OS (P = .07).

Conclusions: Adjuvant PD-1/PD-L1 inhibitors notably enhance MIUC DFS, particularly in lower tract tumors, regardless of PD-L1 status. These findings support immunotherapy, especially anti-PD1, as a valuable adjuvant treatment strategy for high-risk MIUC patients.

高危肌肉侵袭性尿路上皮癌的辅助免疫治疗:随机对照试验的最新荟萃分析
新辅助顺铂化疗后根治性手术是肌肉侵袭性尿路上皮癌(MIUC)的标准治疗方法。Checkmate-274和AMBASSADOR试验表明,辅助免疫治疗可改善无病生存期(DFS)。因此,本荟萃分析旨在评估涉及检查点抑制剂的策略在管理高风险MIUC中的有效性。患者和方法:我们检索了PubMed, Embase, Cochrane, ClinicalTrials.gov, EAU24和ASCO GU摘要,以比较辅助PD-1和PD-L1抑制剂与对照组(安慰剂或观察)治疗MIUC的随机对照试验(rct)。结果包括DFS、≥3级不良事件(ae)和总生存期(OS)。采用I2统计量评估异质性,采用随机效应模型进行分析。结果:来自3个随机对照试验的2220例患者中,1113例(50.14%)接受了辅助免疫治疗。该治疗显著提高了DFS (HR 0.76;95% ci, 0.65-0.90;P < 0.01),尤其是下道肿瘤(HR 0.71;95% ci, 0.56-0.91;P < 0.01)。上尿路亚组无明显的DFS改善(P = 0.28) (P -相互作用= 0.01)。PD-L1状态(p-相互作用= 0.83)和以前的新辅助化疗(p-相互作用= 0.11)对结果没有显著影响。然而,免疫治疗与更高级别≥3 ae相关(RR 1.47;P < 0.01), OS差异无统计学意义(P = 0.07)。结论:与PD-L1状态无关,佐剂PD-1/PD-L1抑制剂可显著增强MIUC DFS,尤其是下道肿瘤。这些发现支持免疫治疗,特别是抗pd1,作为高风险MIUC患者的一种有价值的辅助治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信