Adverse Events and Toxicity of Systemic Treatments for Uveal Melanoma: A Systematic Review

Background/Objectives: The primary objective of this systematic review is to synthesize the available evidence regarding the safety of the various treatment options for advanced uveal melanoma. A thorough understanding of a drug's safety profile enables early identification and management of adverse reactions, thereby preventing clinical deterioration and minimizing the need for dose reduction, treatment delays, or therapy discontinuation. Methods: In accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (Assessing the Methodological Quality of Systematic Reviews) guidelines, this review included all clinical studies that examined the most common adverse events associated with all available systemic treatments for metastatic uveal melanoma. Following the study selection process, nine studies were considered eligible and were included in the review. Results: Treatment with the bispecific antibody was associated with a favorable toxicity profile. The most severe adverse event observed was limited to cutaneous toxicity. Analysis of treatment-related adverse events (TRAEs) of grade ≥3 showed that patient cohorts receiving trametinib, selumetinib, and darovasertib experienced the lowest incidence of severe events (with the exception of creatine phosphokinase elevation observed with selumetinib), suggesting a comparatively more favorable safety profile for these agents. At present, the most robust efficacy data in the metastatic uveal melanoma setting are available for tebentafusp and darovasertib. Conclusions: This study provides the most comprehensive analysis of TRAEs in randomized trials of UM, delineating the toxicity and safety profiles of current therapies to guide personalized treatment decisions.