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.