# Real-World Treatment Patterns and Survival in Uveal Melanoma: A Multicenter Cohort Study by the Turkish Oncology Group (TOG)

## TL;DR

This study examines treatment patterns and survival outcomes in metastatic uveal melanoma patients in Türkiye, highlighting the limited efficacy of chemotherapy and potential benefits of liver-directed and immunotherapy approaches.

## Contribution

The study provides real-world evidence on treatment patterns and survival outcomes in metastatic uveal melanoma from a non-Western population in Türkiye.

## Key findings

- Liver-directed treatments, such as radioembolization, were associated with longer overall survival in metastatic uveal melanoma patients.
- Dual immune checkpoint blockade emerged as an independent favorable prognostic factor for survival.
- HLA-A*02:01 positivity was low, and access to tebentafusp was limited in the studied population.

## Abstract

Uveal melanoma is a rare but aggressive malignancy with a strong tendency to metastasize, particularly to the liver. Once metastasis occurs, treatment options are limited, and survival outcomes remain poor. This multicenter study evaluates real-world outcomes of patients with metastatic uveal melanoma treated across various institutions in Türkiye. We examined both systemic treatment options, including immune checkpoint inhibitors, chemotherapy, and targeted therapies, as well as local treatment approaches, such as liver-directed therapies. By analyzing their effectiveness and survival impact in routine clinical practice, our findings provide a comprehensive overview of current therapeutic strategies. This study offers valuable insights to help clinicians optimize treatment selection and highlights areas where further research and improved therapeutic approaches are needed.

Background/Objectives: Uveal melanoma (UM) is a subtype of melanoma that originates from the uveal layer of the eye (iris, ciliary body, choroid) and is biologically distinct from cutaneous melanoma. The real-world evidence on treatment patterns and survival outcomes, particularly from non-Western populations, remains limited. This study provides a comprehensive national overview of local and systemic management of UM across Türkiye. Methods: This multicenter retrospective cohort study, coordinated by the Turkish Oncology Group (TOG), included patients diagnosed with UM between 2012 and 2025 across 19 tertiary oncology centers. Clinical characteristics, treatment patterns, and outcomes were analyzed. Systemic therapies were subgrouped as immunotherapy or cytotoxic chemotherapy. Progression-free survival (PFS) and overall survival (OS) were assessed by the Kaplan–Meier method; prognostic factors for OS were analyzed by Cox regression. Results: A total of 113 patients were included; 89.4% presented with localized disease. During follow-up, 43.4% developed metastases, predominantly hepatic (93.5%). 47.4% of metastatic patients received liver-directed treatments; the most common treatment was radioembolization, and these treatments were associated with longer OS. Among 59 patients receiving systemic therapy, immunotherapy demonstrated higher ORR and DCR than chemotherapy across treatment lines, although small subgroup sizes limited statistical significance. Dual immune checkpoint blockade emerged as an independent favorable prognostic factor in multivariate analysis. Median OS for metastatic patients was 16 months (95% CI: 9.3–22.7). HLA-A*02:01 was positive in 29.4% of patients tested, and only three patients received tebentafusp. Conclusions: This large national cohort highlights substantial real-world heterogeneity in treatment patterns and confirms the limited efficacy of chemotherapy, the prognostic benefit of dual ICI therapy, and the potential survival advantage of liver-directed treatments in selected patients. Low HLA-A*02:01 positivity and limited access to tebentafusp remain major challenges in Türkiye. These findings provide an essential benchmark for improving treatment strategies in metastatic UM.