Gazzoni Gabriela, Michelon Isabella, Vilbert Maysa, Oliveira João Pedro, Dacoregio Maria Inez, Reis Pedro C A, Braga Marcelo A P, Simões Clara Aleixo, de Oliveira Lilia Maria Lima, Zibelman Matthew, Cardoso Ana Paula
Department of Internal Medicine, Institute of Medical Assistance to the State Public Servant (IAMSPE), São Paulo, Brazil.
Division of Hematology and Oncology, University of Virginia Comprehensive Cancer Center, Charlottesville, Virginia, USA.
Urol Oncol. 2025 Oct;43(10):595.e1-595.e11. doi: 10.1016/j.urolonc.2025.05.016. Epub 2025 Jun 30.
Enfortumab vedotin (EV) is an antibody-drug conjugate that binds nectin-4, a cell-adhesion molecule highly expressed in urothelial carcinoma (UC) and epidermal keratinocytes. Dermatologic events have become important EV-related toxicities in clinical trials and observational studies. We conducted a systematic review and meta-analysis on dermatological toxicity in UC patients treated with EV.
We systematically searched PubMed, Cochrane, and Embase for clinical trials (CT) and observational studies reporting EV-related cutaneous toxicities in UC patients. We investigated all-grade and grade ≥ 3 treatment-related adverse events (TRAE) and severe cutaneous adverse reactions (SCAR) in UC patients. The outcomes were presented as overall incidence rates and 95% confidence intervals (95% CI). Statistical analyses were performed using R software.
30 studies comprising 2,554 participants were included, of which 72% (n = 1,845) were male. In a pooled analysis, all-grade skin reaction rate was 49% (95% CI 42%-56%), and grade ≥ 3 events were observed in 10% (95% CI 8%-13%) of cases. The incidence of all-grade and grade ≥ 3 SCAR was 19% (95% CI 16%-23%) and 5% (95% CI 3%-7%), respectively. The frequency of alopecia, pruritus, and dry skin were as follows: 29%, 26%, and 22%. The incidence of all-grade rash was 27%, with maculopapular rash (19%), and erythematous rash (6%) as the most common types.
To our knowledge, this is the first meta-analysis to characterize EV-related dermatological toxicities. While most cases are manageable, patients on EV should be closely monitored for cutaneous AEs to prevent serious complications and to maintain treatment efficacy.
恩杂鲁胺（EV）是一种抗体药物偶联物，可与NECTIN - 4结合，NECTIN - 4是一种在尿路上皮癌（UC）和表皮角质形成细胞中高度表达的细胞粘附分子。在临床试验和观察性研究中，皮肤事件已成为与EV相关的重要毒性反应。我们对接受EV治疗的UC患者的皮肤毒性进行了系统评价和荟萃分析。
我们系统检索了PubMed、Cochrane和Embase，以查找报告UC患者中与EV相关的皮肤毒性的临床试验（CT）和观察性研究。我们调查了UC患者所有级别的和≥3级的治疗相关不良事件（TRAE）以及严重皮肤不良反应（SCAR）。结果以总发生率和95%置信区间（95%CI）表示。使用R软件进行统计分析。
纳入了30项研究，共2554名参与者，其中72%（n = 1845）为男性。在汇总分析中，所有级别的皮肤反应率为49%（95%CI 42% - 56%），10%（95%CI 8% - 13%）的病例观察到≥3级事件。所有级别和≥3级SCAR的发生率分别为19%（95%CI 16% - 23%）和5%（95%CI 3% - 7%）。脱发、瘙痒和皮肤干燥的发生率如下：29%、26%和22%。所有级别的皮疹发生率为27%，其中最常见的类型为斑丘疹（19%）和红斑疹（6%）。
据我们所知，这是第一项对与EV相关的皮肤毒性进行特征描述的荟萃分析。虽然大多数病例是可控的，但接受EV治疗的患者应密切监测皮肤不良事件，以预防严重并发症并维持治疗效果。
