What should be the first line treatment for metastatic uveal melanoma?

There is no consensus for frontline treatment of metastatic uveal melanoma. A clinical trial would be recommended for all patients if possible. If the disease is only within the liver, consideration of liver directed therapy would be reasonable. For metastatic disease beyond the liver checkpoint immunotherapy (ipilimumab, pembrolizumab, nivolumab) are sometimes given however their activity has been very low. A clinical trial would be preferred and worth noting that the cooperative group ALLIANCE A091201 study is evaluating cabozantinib and can be opened through any practice associated with a national cooperative group.

My first step is to check HLA-A*02:01. If matched, then tebentafusp is my clear first choice given the OS benefit in the randomized phase III study. If HLA is unmatched, then I look to see if liver-only disease vs extra-hepatic. If liver only, hepatic perfusion (aka Hepzato) is a good option. Can also consider Hepzato with ipilimumab + nivolumab per the recent Chopin study if disease is more extensive. Hepzato is not an option for everyone, so in HLA-unmatched patients, we will use ipi-nivo by itself, though we know outcomes are not great, so we will also look for trial options in this setting. We saw the darovasertib + crizotinib data at ASCO this year, so that looks like a promising option for HLA-unmatched patients as a possible 1L optio...