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. 2025 Mar 3;8(3):e250250.
doi: 10.1001/jamanetworkopen.2025.0250.

Enfortumab Vedotin With or Without Pembrolizumab in Metastatic Urothelial Carcinoma: A Systematic Review and Meta-Analysis

Shugo Yajima  1 , Kohei Hirose  1 , Hitoshi Masuda  1
Affiliations

Enfortumab Vedotin With or Without Pembrolizumab in Metastatic Urothelial Carcinoma: A Systematic Review and Meta-Analysis

Shugo Yajima et al. JAMA Netw Open. .

Abstract

Importance: Metastatic urothelial carcinoma (mUC) presents a therapeutic challenge with poor outcome. Enfortumab vedotin has emerged as a promising treatment, necessitating a comprehensive evaluation of its effectiveness and safety.

Objective: To synthesize the available evidence on enfortumab vedotin, both as monotherapy and in combination with pembrolizumab, as an mUC treatment for the purpose of guiding clinical decision-making and future research.

Data sources: Cochrane Library, MEDLINE (via PubMed), Google Scholar, and Web of Science were searched from database inception to August 31, 2024. Major conference abstracts from 2019 to 2024 were also included. Search strategy used a combination of Medical Subject Heading terms and free-text keywords related to mUC and enfortumab vedotin.

Study selection: Randomized clinical trials and prospective studies investigating enfortumab vedotin in adult patients with mUC were included. Eleven studies met the inclusion criteria.

Data extraction and synthesis: Two independent reviewers extracted data and assessed study quality using the Cochrane Risk of Bias tool 2 and Risk of Bias in Non-Randomized Studies of Interventions tool. The meta-analysis used a random effects model, while a network meta-analysis was performed using a frequentist approach.

Main outcomes and measures: Primary outcomes were disease control rate (DCR), objective response rate (ORR), and 1-year survival rate.

Results: The 11 included studies (3 randomized clinical trials [27.3%] and 8 nonrandomized prospective studies [72.7%]) involved 2128 patients. Of these patients, 563 (26.5%) received enfortumab vedotin plus pembrolizumab, 814 (38.3%) received enfortumab vedotin without pembrolizumab, and 751 (35.3%) received chemotherapy. Enfortumab vedotin plus pembrolizumab was associated with a pooled DCR of 86% (95% CI, 83%-89%), ORR of 68% (95% CI, 64%-71%), and a 1-year survival rate of 79% (95% CI, 75%-82%). Enfortumab vedotin monotherapy had a pooled DCR of 73% (95% CI, 70%-76%), ORR of 43% (95% CI, 40%-47%), and a 1-year survival rate of 52% (95% CI, 48%-56%). Network meta-analysis revealed that enfortumab vedotin plus pembrolizumab significantly outperformed chemotherapy in ORR (odds ratio [OR], 3.47; 95% CI, 1.49-8.09; P = .004) and 1-year survival (OR, 2.32; 95% CI, 1.75-3.06; P < .001).

Conclusions and relevance: In this systematic review and meta-analysis, enfortumab vedotin plus pembrolizumab showed high response rates in first-line settings, while enfortumab vedotin monotherapy was associated with clinical benefit in later lines of therapy. These findings underscore the importance of personalized treatment approaches, and future research is warranted to refine enfortumab vedotin-based therapies for mUC management.

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Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure 1.
Figure 1.. Flow Diagram of Literature Search and Study Selection
From 801 initial records, 11 studies were ultimately included after removing duplicates, screening abstracts, and assessing full-text eligibility.
Figure 2.
Figure 2.. Disease Control Rate (DCR), Objective Response Rate (ORR), 1-Year Survival Rate, and High-Grade Adverse Events (AEs) for Enfortumab Vedotin Monotherapy in Metastatic Urothelial Carcinoma
Plots show individual study results and pooled estimates with 95% CIs. Squares represent individual study effect sizes, and diamonds represent the pooled or overall effect estimates from meta-analysis, with the width of the diamond showing the 95% CI.
Figure 3.
Figure 3.. Disease Control Rate (DCR), Objective Response Rate (ORR), 1-Year Survival Rate, and High-Grade Adverse Events (AEs) for Enfortumab Vedotin Plus Pembrolizumab in Metastatic Urothelial Carcinoma
Plots show individual study results and pooled estimates with 95% CIs. Squares represent individual study effect sizes, and diamonds represent the pooled or overall effect estimates from meta-analysis, with the width of the diamond showing the 95% CI.
Figure 4.
Figure 4.. Results of Network Meta-Analysis Comparing Enfortumab Vedotin Monotherapy, Enfortumab Vedotin Plus Pembrolizumab, and Chemotherapy in Metastatic Urothelial Carcinoma
Plots show odds ratio (ORs) with 95% CIs. AE indicates adverse event; DCR, disease control rate; ORR, objective response rate.
See this image and copyright information in PMC

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