Recognition and management of organ-specific toxicities associated with enfortumab vedotin plus pembrolizumab and erdafitinib in locally advanced or metastatic urothelial carcinoma.

Abstract

Enfortumab vedotin plus pembrolizumab and erdafitinib have transformed the treatment of locally advanced or metastatic urothelial carcinoma (la/mUC) but are associated with distinct and, in some cases, overlapping toxicities that may lead to treatment discontinuation and impaired clinical outcomes if not recognised and managed promptly. The heterogeneous presentation and multifactorial mechanisms underlying these adverse events often make attribution challenging, delaying diagnosis and urgent action when needed. Coordinated multidisciplinary management of these toxicities is crucial to minimise morbidity while preserving treatment benefit. This narrative review summarises the current evidence on the identification, differential diagnosis, monitoring and management of the most clinically relevant toxicities associated with enfortumab vedotin plus pembrolizumab and erdafitinib. Practical organ-based guidance is provided for supportive care, dose modification and treatment discontinuation and rechallenge, as well as referral for specialist management, with emphasis on red flags that should prompt urgent multidisciplinary assessment.