Recent Clinical Advances in the Treatment of Cutaneous Melanoma

Metastatic melanoma represents an aggressive tumor with overall poor prognosis. Targeted agents and immunotherapy have become the standard of care. Approximately 50-60 % of melanomas harbor BRAF mutations. Vemurafenib and dabrafenib are BRAF inhibitors, a group of drugs that will certainly expand, and obtained FDA approval after showing increased response rate (ORR), progression free survival (PFS) and overall survival (OS) when compared to chemotherapy. Trametinib was the first MEK inhibitor approved as single agent in 2013, but when combined with BRAF inhibition, results are even improved. Immunotherapy with IL-2 received approval in 1999 based on phase II data mainly due to its potentially long term response but proved to be quite toxic. Check point inhibitors can block CTLA-4 (ipilimumab) or PD-1 (nivolumab and pembrolizumab) thus interrupting the brakes that stop the immune system against malignant cells. Long duration of response resembles that of IL-2 but with more acceptable toxicity. Given the complexity of this rapidly evolving field we will try to provide the reader with a summary of the key clinical aspects derived from the use of these new agents in daily practice.