Severe Cutaneous Toxicity in A 67-Year-Old Patient with Metastatic Urothelial Carcinoma Undergoing Therapy with Enfortumab Vedotin and Pembrolizumab.

Abstract

Introduction: Enfortumab vedotin (EV) combined with pembrolizumab (EV+P) is a promising first-line therapy for metastatic urothelial carcinoma. While it has shown significant efficacy, severe cutaneous adverse events such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported. We present this case as another example of severe skin off-target toxicity associated with this treatment, emphasising the importance of recognising this potential complication.

Case description: A 67-year-old male with metastatic urothelial carcinoma, chronic kidney failure and liver cirrhosis presented with fever, respiratory symptoms and a pruritic rash after two doses of EV+P. The rash rapidly worsened, leading to extensive skin desquamation affecting 20-30% of his body surface area. Skin biopsies confirmed SJS with early-stage TEN (SJS/TEN overlap). The patient was treated with high-dose intravenous steroids, empirical antibiotics for neutropenia and intensive topical care. Significant re-epithelialisation occurred by day 13, and the patient was discharged on day 15 with cessation of EV+P therapy.

Conclusion: This case demonstrates the potential for severe cutaneous toxicity in patients receiving EV+P, especially those with complex comorbidities. Early recognition and prompt, aggressive management with systemic corticosteroids are essential for improving outcomes. The case highlights the need for vigilance in monitoring for such adverse events and reporting them to improve patient safety.

Learning points: High clinical suspicion recognition of early signs of dermolysis is essential in managing severe cutaneous toxicity associated with enfortumab vedotin.A multidisciplinary approach the management of Stevens-Johnson syndrome/toxic epidermal necrolysis should involve a multidisciplinary team, especially in patients with complex comorbidities.Pharmacovigilance continuous monitoring and prompt reporting of adverse events to health authorities are vital for improving patient safety and therapeutic outcomes.