• Patrick Terheyden, Angela Krackhardt, and Thomas Eigentler.
• Department of Dermatology, Allergology and Venerology, University Medical Center Schleswig-Holstein, Campus Lübeck; Department of Internal Medicine III, Hematology and Oncology, University Hospital rechts der Isar, TU München; Department of Dermatology University of Tübingen.
• Dtsch Arztebl Int. 2019 Jul 22; 116 (29-30): 497-504.

BackgroundThe systemic treatment of metastatic melanoma has improved considerably with the introduction of new, targeted substances and immune checkpoint inhibitors. This article presents treatment options for advanced inoperable melanoma and in the setting of adjuvant treatment after complete metastasectomy.MethodsThe data for analysis were derived from a selective literature search in PubMed and a search for systematic reviews in the Cochrane Library.ResultsImmune checkpoint inhibitors, which target the cytotoxic T-lymphocyte antigen or the "programmed death" (PD) receptor, activate T-cells and other immune cells, so that the body's own immune system attacks the melanoma. In unselected patients, immune checkpoint inhibition using nivolumab improved overall survival compared with dacarbazine (hazard ratio [HR]: 0.42; P<0.001). The antibody pem- brolizumab also led to better overall survival than ipilimumab (HR 0.68; P<0.001). Combination treatment with anti-CTLA-4 and anti-PD-1 antibodies improved overall survival even more than ipilimumab monotherapy, albeit at the cost of greater toxic- ity (HR 0.55; P<0.001). Another treatment approach aims to inhibit intracellular signal transduction in the melanoma cells. For patients with a BRAF-V66 mutation, combination treatments with BRAF/MEK inhibitors led to a rapid response in most cases (64-75%). In principle, the novel treatments are also effective in patients with cerebral metastases. In the adjuvant setting, both immune checkpoint inhibitors and BRAF/MEK inhibitors reduced the risk of recurrence by about 50%.ConclusionHigh-quality studies show that the new substances are clinically effective in the palliative and adjuvant treatment of melanoma.

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