Systemic treatment of non-resectable melanoma

Among established therapies for inoperable melanoma are immune checkpoint inhibition with cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and lymphocyte activating gene 3 (LAG-3) inhibitors and, in the presence of a BRAF V600 mutation, targeted therapy with BRAF/MEK inhibition. These systemic treatments have led to a significant improvement in the clinical outcome of metastatic melanoma patients. However, metastatic melanoma remains a therapeutic challenge, especially in cases of disease progression under systemic therapy. In this review, the established systemic treatments, e.g., immune checkpoint inhibition, targeted therapy, and local treatment options are presented. New therapy strategies such as sequence therapy and combination therapy for BRAF-mutated melanoma as well as new drugs in clinical studies and the increasingly personalized melanoma therapy are introduced.