A retrospective meta-analysis suggests that tebentafusp promotes better overall survival in patients with metastatic uveal melanoma when compared to other systemic treatments, including combined immune checkpoint blockade (ICB), although its use may be limited to patients with a particular human leukocyte antigen (HLA) subtype.
Study design
This systematic review and meta-analysis included 55 randomized controlled trials, clinically controlled trials, non-controlled clinical trials, retrospective studies, and large case series (N >10) of patients with metastatic uveal melanoma treated with systemic therapy through December 2021. Eligible studies provided Kaplan–Meier curves or individual patient data for overall survival (OS) from the start time of systemic therapy. The efficacy of tebentafusp was compared with that of other systemic treatments, particularly combined ICB, using population-adjusted methods, including a regression-based simulated treatment comparison (STC), a matching-adjusted indirect comparison (MAIC), and a 2-stage MAIC (2SMAIC).
Outcomes
Among the 2682 patients with OS data, tebentafusp was associated with greater OS (median 22.4 months) than combined ICB (median 15.7 months) and other treatments. In an unadjusted model, tebentafusp also reduced the risk of death compared to combined ICB with a hazard ratio of 0.641; the effect was more pronounced with population adjustment, yielding an HR of 0.284 in the STC model, 0.386 with MAIC, and 0.378 with 2SMAIC.
Limitations
These study outcomes should be interpreted with caution due to the retrospective nature of the meta-analysis and heterogeneity of the included studies. Baseline information was only available for certain patient data (i.e., age, sex, localization of metastases, Eastern Cooperative Oncology Group performance score, lactate dehydrogenase levels, pretreatments, and subsequent therapies). In addition, tebentafusp is designed to recognize a particular peptide sequence, so it is only effective in and currently being used for patients with the HLA-A*02:01 subtype; HLA testing is not routinely performed when considering ICB. A prospective, randomized controlled trial directly comparing OS between tebentafusp and combined ICB would provide more definitive evidence of the effectiveness of tebentafusp.
Clinical significance
Tebentafusp may offer a survival benefit compared to combined ICB for patients with metastatic uveal melanoma, especially those who are HLA-A*02:01-positive. For these patients, tebentafusp should be considered as a preferred first-line therapy.
Financial Disclosures: Dr. Lauren Dalvin discloses financial relationships with Leonard and Mary Lou Hoeft Career Development Award Fund, National Cancer Institute, and National Center for Advancing Translational Science (Grant Support).