Clinical outcomes of tebentafusp in metastatic uveal melanoma: a systematic review and single-arm meta-analysis.

OBJECTIVE

To evaluate efficacy and safety of tebentafusp in patients with metastatic uveal melanoma.

METHOD: A systematic search was conducted in five databases (Pubmed, Embase, Web of Science, Scopus, and the Cochrane Library) to find articles that evaluate the effectiveness of tebentafusp in patients with metastatic uveal melanoma, from the establishment of the databases to October 13, 2025. Additionally, clinical trials were searched on clinicaltrials.gov. Meta-analyses were performed to evaluate the frequencies of progression-free survival (PFS), overall survival (OS), partial response (PR), stable disease (SD), progressive disease (PD), objective response rate (ORR), disease control rate (DCR), Cytokine release syndrome (CRS) and treatment-related adverse events (trAEs).

RESULTS

A total of six studies were initially enrolled, involving 850 participants. Among them, 631 patients with evaluable uveal melanoma who received tebentafusp treatment were ultimately included in this meta-analysis (mean age, 60.56 years; 425 [50%] men). The median OS and PFS were 21.3 months and 3.6 months, respectively. The PR, SD, PD,ORR and DCR were 0.09 [95% confidence interval (CI), 0.05 to 0.14], 0.39 (95% CI, 0.35 to 0.43), 0.79 (95% CI, 0.32 to 0.97), 0.09 (95% CI, 0.06 to 0.13) and 0.27 (95% CI, 0.20 to 0.36), respectively. The any grade cytokine release syndrome rate, grade ≥ 3 cytokine release syndrome rate, any grade trAEs rate and grade ≥ 3 trAEs rate were 0.88 (95% CI, 0.84 to 0.91), 0.02 (95% CI, 0.01 to 0.06), 0.98 (95% CI, 0.75 to 1.00) and 0.41 (95% CI, 0.17 to 0.71), respectively. The most common adverse reactions include pyrexia 0.83 (95% CI, 0.79 to 0.86), nausea 0.58 (95% CI, 0.42 to 0.73), fatigue 0.54 (95% CI, 0.38 to 0.70), pruritus 0.72 (95% CI, 0.65 to 0.78), chills 0.60 (95% CI, 0.47 to 0.71), dry skin 0.43 (95% CI, 0.25 to 0.63), hypotension 0.41 (95% CI, 0.36 to 0.45).

CONCLUSION

The research results show that tebentafusp exhibits modest but potentially meaningful survival benefit despite low response rates for metastatic uveal melanoma patients. Although adverse events often occur, such as cytokine release syndrome of grade three or above, they are usually manageable and controllable. Given the limitations of this study, it is crucial to conduct further multi-center randomized controlled trials and increase the sample size to further verify our results.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD420251234508. Available from https://www.crd.york.ac.uk/PROSPERO/view/CRD420251234508.