Tebentafusp in Metastatic Uveal Melanoma: A Meta-analysis

Tebentafusp is the first systemic therapy to improve survival outcomes for patients with HLA-A*02:01-positive metastatic uveal melanoma (mUM). However, outside the pivotal study, limited data for tebentafusp are reported in literature.

To evaluate the efficacy and safety of tebentafusp in patients with human leukocyte antigen (HLA)-A*02:01-positive mUM across cohort studies and clinical trials.

PubMed, EMBASE, Cochrane, and Web of Science (up to July 2025) were surveyed for studies evaluating tebentafusp in patients with HLA-A*02:01-positive mUM. A meta-analysis using a random-effects model and the inverse variance method was conducted; Kaplan-Meier curves, where available, were used to recreate the time-to-event data. The primary objective was efficacy, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The secondary objective was to evaluate all-grade and severe (grade ≥ 3 or higher) adverse events (AEs).

A total of 997 patients from 12 cohorts were included. Using reconstructed time-to-event outcomes from published Kaplan-Meier curves, the estimated median PFS was 3.9 months (95% confidence interval [CI] 3.77-4.92). The median OS was 21.2 months (95% CI 19.2-23.1). When stratified by study design, the median OS was similar between prospective and retrospective studies: 21.2 months (95% CI 19.2-23.8) and 21.1 months (95% CI 18.1-33.6), respectively. Likewise, median progression-free survival (PFS) was comparable between prospective and retrospective studies: 3.8 months (95% CI 3.25-5.5) and 3.9 months (95% CI 3.8-4.9), respectively. The rate of cytokine- and cutaneous-mediated events was 67% (95% CI 45-84; I² = 94.4%) and 64% (95% CI 28-89; I² = 97.3%), respectively. Severe AEs for cytokine-mediated events were 3% (95% CI 1-13; I² = 87.6%), and cutaneous-mediated events were 11% (95% CI 8-14; I² = 0%). The discontinuation rate was 2% (95% CI 1-4; I² = 0%).

Tebentafusp for patients with HLA-A*02:01-positive mUM is associated with improved survival outcomes and manageable toxicity. These findings support tebentafusp as the standard of care for this patient population.