Network meta-analysis compares therapies for liver metastatic uveal melanoma
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Key Takeaway
Consider liver-directed therapy with immune checkpoint inhibitors as potentially most effective for liver metastatic uveal melanoma.
This is a systematic review and network meta-analysis of therapeutic modalities for patients with liver metastatic uveal melanoma. The review synthesized evidence on tebentafusp, immune checkpoint inhibitors, targeted therapy, chemotherapy, liver-directed therapy, and their combinations. The authors found that liver-directed therapy combined with immune checkpoint inhibitors was the most effective for both overall survival and progression-free survival. Tebentafusp showed the second-best overall survival but the worst progression-free survival. Immune checkpoint inhibitors were inferior to tebentafusp for overall survival but superior for progression-free survival. Regional liver-directed therapy demonstrated more favorable outcomes compared with conventional systemic chemotherapy, targeted therapy, or their combination. The authors noted that emerging immunotherapies and novel targeted agents could not be included due to the absence of comparative trials or ongoing investigations. Practice relevance is limited to existing evidence, and future comparative studies incorporating emerging therapies are warranted.
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View Original Abstract ↓
ObjectiveTo evaluate the efficacy of different therapeutic modalities in the treatment of metastatic uveal melanoma (mUM).MethodsAccording to PRISMA criteria, We identified relevant randomized controlled trials (RCTs) by searching PubMed, Embase, and The Cochrane Library through March 31, 2026. Patients with liver metastatic uveal melanoma were enrolled. The analysis of clinical prognostic factors was performed using R 4.2.0. The main outcomes measured were overall survival (OS) and progression-free survival (PFS).ResultsA total of 16 articles were screened between 2000 and 2026, involving 2585 patients. The trials evaluated eight treatment approaches: tebentafusp, immune checkpoint inhibitors (ICIs), targeted therapy, targeted therapy plus chemotherapy, chemotherapy, liver-directed therapy (LDT), liver-directed therapy combined with ICIs, and liver-directed therapy plus chemotherapy. The results of the included trials showed that in terms of overall survival and progression-free survival, the liver-directed therapy combined with ICIs were the most effective regardless of the HLA genotype. Tebentafusp showed the second-best OS but the worst PFS among the compared treatments. Immune checkpoint inhibitors were inferior to tebentafusp in improving OS but were superior in PFS. Furthermore, compared with conventional systemic chemotherapy, targeted therapy, or their combination, regional liver-directed therapy demonstrated more favorable outcomes in both OS and PFS. Emerging immunotherapies (e.g., tumor vaccines, oncolytic virotherapy, tumor-infiltrating lymphocytes) and novel targeted agents could not be included in the NMA due to the absence of comparative trials or ongoing investigations.ConclusionThe liver-directed therapy combined with ICIs achieved the best results compared to Tebentafusp, ICIs and other therapeutic modality for OS and PFS extension in metastatic uveal melanoma based on available data. Future comparative studies incorporating emerging therapies are warranted.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD420261393862.
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