| アブストラクト | BACKGROUND AND OBJECTIVE: 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. METHODS: 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. KEY FINDINGS AND LIMITATIONS: 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; p = 0.013), male gender (aOR 1.51, 95% CI 1.19-1.91; p < 0.001), and chemotherapy (aOR 1.51, 95% CI 1.19-1.91; p < 0.001). Occurrence of SJS/TEN was associated with older age (65-80 yr: aOR 2.06, 95% CI 1.15-3.68; p = 0.015; >80 yr: aOR 2.17, 95% CI 1.04-4.53; p = 0.038) and hypertension (aOR 1.65, 95% CI 1.03-2.65; p = 0.038). CONCLUSIONS AND CLINICAL IMPLICATIONS: 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. PATIENT SUMMARY: 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. |
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