Pan Yun, Yu Rentao, Huang Hong, Chen Xiaoli, Gou Xin, Chen Aijun
The Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
The Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Eur Urol Open Sci. 2025 Aug 15;80:5-13. doi: 10.1016/j.euros.2025.08.001. eCollection 2025 Oct.
Enfortumab vedotin (EV), an antibody-drug conjugate targeting nectin-4 and linked to monomethyl auristatin E, has shown efficacy in metastatic urothelial carcinoma. However, emerging evidence has identified severe cutaneous adverse events (cAEs), particularly Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). To date, no comprehensive analysis of cAEs associated with EV has been reported. This study aims to investigate the incidence, onset time, and factors associated with cAEs, particularly SJS/TEN, in patients treated with EV, using data from the U.S. Food and Drug Administration's Adverse Event Reporting System.
This retrospective study analyzed data from January 1, 2020 to November 1, 2024, covering 2736 patients. A disproportionality analysis and positive signal detection were used to assess the correlation between EV and adverse events (AEs). Logistic regression was employed to evaluate the factors associated with the occurrence of AEs.
Among the 2736 patients analyzed, a total of 6520 AEs were reported. Skin-related AEs were most frequent, accounting for 1027 cases (37.54%), with SJS/TEN occurring in 8.59% of cases. Our analysis shows that most cAEs occurred within 30 d of starting EV treatment, with SJS/TEN onset peaking at 14 d. Within the category of skin and subcutaneous tissue disorders, 54 skin-related AEs had one or more positive signals, and 43 cases had three or more positive signals. The factors associated with skin-limited AEs included prior immunotherapy (adjusted odds ratio [aOR] 1.90, 95% confidence interval [CI] 1.15-3.15; = 0.013), male gender (aOR 1.51, 95% CI 1.19-1.91; < 0.001), and chemotherapy (aOR 1.51, 95% CI 1.19-1.91; < 0.001). Occurrence of SJS/TEN was associated with older age (65-80 yr: aOR 2.06, 95% CI 1.15-3.68; = 0.015; >80 yr: aOR 2.17, 95% CI 1.04-4.53; = 0.038) and hypertension (aOR 1.65, 95% CI 1.03-2.65; = 0.038).
Our study highlights a higher incidence of cAEs during EV treatment, particularly severe cAEs such as SJS/TEN. These findings underscore the need for vigilant monitoring and proactive management of these AEs in clinical practice, especially in high-risk populations.
Our study shows that a significant number of patients treated with enfortumab vedotin experienced serious skin reactions. We found that certain factors, such as previous immunotherapy and being male, increased the risk of these reactions. These imply that doctors need to watch patients closely when using this drug.
恩扎妥昔单抗（EV）是一种靶向连接Nectin-4和单甲基奥瑞他汀E的抗体偶联药物，已在转移性尿路上皮癌中显示出疗效。然而，新出现的证据表明存在严重的皮肤不良事件（cAE），尤其是史蒂文斯-约翰逊综合征（SJS）和中毒性表皮坏死松解症（TEN）。迄今为止，尚未有关于与EV相关的cAE的全面分析报道。本研究旨在利用美国食品药品监督管理局不良事件报告系统的数据，调查接受EV治疗的患者中cAE的发生率、发病时间以及与cAE相关的因素，尤其是SJS/TEN。
这项回顾性研究分析了2020年1月1日至2024年11月1日的数据，涵盖2736例患者。采用不成比例分析和阳性信号检测来评估EV与不良事件（AE）之间的相关性。使用逻辑回归评估与AE发生相关的因素。
在分析的2736例患者中，共报告了6520例AE。皮肤相关AE最为常见，占1027例（37.54%），其中SJS/TEN占8.59%。我们的分析表明，大多数cAE发生在开始EV治疗后的30天内，SJS/TEN发病高峰在14天。在皮肤和皮下组织疾病类别中，54例皮肤相关AE有一个或多个阳性信号，43例有三个或更多阳性信号。与局限性皮肤AE相关的因素包括既往免疫治疗（调整后的优势比[aOR]为1.90，95%置信区间[CI]为1.15 - 3.15；P = 0.013）、男性（aOR为1.51，95% CI为1.19 - 1.91；P < 0.001）和化疗（aOR为1.51，95% CI为1.19 - 1.91；P < 0.00）。SJS/TEN的发生与年龄较大（65 - 80岁：aOR为2.06，95% CI为1.15 - 3.68；P = 0.015；>80岁：aOR为2.17，95% CI为1.04 - 4.53；P = 0.038）和高血压（aOR为1.65，95% CI为1.03 - 2.65；P = 0.038）有关。
我们的研究强调了EV治疗期间cAE的发生率较高，尤其是严重的cAE，如SJS/TEN。这些发现强调了在临床实践中对这些AE进行密切监测和积极管理的必要性，特别是在高危人群中。
我们的研究表明，大量接受恩扎妥昔单抗治疗的患者经历了严重的皮肤反应。我们发现某些因素，如既往免疫治疗和男性，会增加这些反应的风险。这意味着医生在使用这种药物时需要密切观察患者。
