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

## TL;DR

This paper reviews the safety of different treatments for uveal melanoma, highlighting which therapies have the best safety profiles.

## Contribution

The study provides a comprehensive analysis of treatment-related adverse events in randomized trials for uveal melanoma.

## Key findings

- Bispecific antibody treatment showed a favorable toxicity profile with limited severe adverse events.
- Tebentafusp and darovasertib have the most robust efficacy data in metastatic uveal melanoma.
- Trametinib, selumetinib, and darovasertib had the lowest incidence of grade ≥3 adverse events.

## Abstract

Uveal melanoma is a highly aggressive malignancy associated with a poor prognosis. Systemic therapeutic approaches for uveal melanoma encompass chemotherapy, immunotherapy, targeted therapies, bispecific antibodies, antibody–drug conjugates, and combination treatment regimens. The primary objective of this systematic review is to synthesize the available evidence regarding the safety profiles of these therapeutic strategies in advanced uveal melanoma, thereby providing clinicians with a comprehensive and authoritative overview of the current evidence base.

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.