• Ocular Pathology/Oncology

    Review of: Overall survival benefit with tebentafusp in metastatic uveal melanoma

    Nathan P, Hassel J, Rutkowski P, et al. New England Journal of Medicine, September 2021

    Patients with metastatic uveal melanoma who received tebentafusp had significantly higher 1-year survival rates than patients who received pembrolizumab, ipilimumab, or dacarbazine.

    Study design

    This open-label, phase 3 randomized clinical trial assigned patients with metastatic uveal melanoma in a 2:1 fashion to receive either tebentafusp or the investigator's choice of pembrolizumab, ipilimumab, or dacarbazine. Eligible patients were adults with histopathologic or cytologic evidence of metastatic uveal melanoma, no prior exposure to systemic or liver-directed cancer therapy, favorable Eastern Cooperative Oncology Group performance score of 0 or 1, and 1 or more measurable lesions. Only HLA-A*02:01–positive patients were included. Time-to-event analysis was used to assess overall survival.

    Outcomes

    Of 252 patients assigned to tebentafusp compared with 126 patients assigned to the investigator’s choice, tebentafusp was associated with improved 1-year overall survival of 73% vs 59% for the other groups. Tebentafusp was also associated with improved progression-free survival of 31% compared with 19% at 6 months. The objective response rate with tebentafusp was 9% compared with 5% in the investigator’s choice group. The most common side effects associated with tebentafusp were cytokine-release syndrome and cutaneous rash.

    Limitations

    Only HLA-A*02:01–positive patients were included in this study, which accounts for approximately 45% of the US and European populations with the disease. Therefore, results are applicable to only a subset of patients affected by uveal melanoma. Study results should be interpreted with caution due to the use of single-agent therapies in the control group. Combination therapy, such as ipilimumab plus nivolumab, has demonstrated objective response rates exceeding 9% and may be a more important benchmark for comparison with tebentafusp to determine its role as first-line therapy for metastatic uveal melanoma.

    Clinical significance

    Tebentafusp was associated with improved overall survival for treatment-naïve uveal melanoma patients compared with investigator’s choice single-agent therapy. These results offer renewed hope for a subset of HLA-A*02:01–positive patients with metastatic uveal melanoma. Future randomized, prospective studies comparing tebentafusp with combination therapy would be useful to guide choice of first-line treatment. Ongoing research is required to reach a cure for all patients with uveal melanoma.