Abstract
Essential progress has been achieved in systemic treatment of metastatic melanoma during the last few years. Based on the high prevalence of the activating BRAF V600 mutation (∼45%) and the activating NRAS mutation (∼15%), specific kinase inhibitors have been developed for activated BRAF and MEK. Prolongation of survival and remission rates ∼50% and more have been observed in phase III trials with the BRAF inhibitors vemurafenib and dabrafenib, and slightly less activity for the MEK inhibitor trametinib. Interestingly, the combination of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib seems to postpone development of resistance and seems to be superior to single agent treatment without increasing the toxicity. All these drugs are efficacious in patients with liver metastasis carrying the BRAF mutation. Another new approach is immunotherapy with immune checkpoint inhibitors, like the CTLA-4 inhibitor ipilimumab and PD-1 inhibitors. Both drugs lead to a continuous activation of functional T cell responses against the tumor, and ∼15–30% of patients seem to benefit from this kind of treatment with long term stabilization of the disease. These immunotherapies work likewise in patients with liver metastasis.
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