Adjuvant treatments in melanoma

Summary For decades, interferon-alpha (IFN-α) has been the only option in the adjuvant treatment of high-risk melanoma. De spite numerous clinical trials and meta-analyzes, IFN-α is not yet a gold standard. It indeed showed benefit in progression-free survival (PFS) and to a lesser extent in overall survival (OS) but at the cost of high toxicity. The emergence of new, revolutionary therapies in the treatment of metastatic melanoma, like immunotherapy (check point inhibitors - CTLA4 and PD1 inhibitors) and targeted therapies (BRAF and MEK inhibitors), led to considering their potential effect in adjuvant/preventive use. A number of phase II and phase III trials analyzed the adjuvant application of targeted therapies and immunothera pies in completely resected stage III melanoma (IIIA, IIIB, IIIC) and stage IV melanoma (PD1 inhibitor nivolumab). They showed a clear benefit in relapse-free survival (RFS) and overall survival (OS). This led to a change in guidelines for adju vant treatment of melanoma and approval of immunotherapy and targeted therapy by the FDA (Food and Drug Adminis -tration) and EMA (European medicines agency) in the indications mentioned above. Further trials are underway in other high-risk stages (like IIC) and in neoadjuvant treatment of stage III melanoma.