Last update:
04-Feb-2015

Until recently, the only treatment options for metastatic melanoma were immunotherapy with high dose interleukin-2 (IL-2), which has severe adverse effects and is not widely available, and palliative chemotherapy with dacarbazine, which has not been shown to improve survival. The prognosis was poor and for over 20 years no single drug or drug combination was introduced that led to improvement in overall survival. The clarification over the past few years of the molecular biology of malignant melanoma has led to the development and successful clinical use of the BRAF and MEK inhibitors. In addition, the understanding of the mechanisms of tumor evasion from immune surveillance led to the development of anti-CTLA-4 and anti-PD-1 monoclonal antibodies, which are active in melanoma and are already being tested for the treatment of a variety of solid tumors. This explosion in new knowledge has resulted for the first time in improved survival and better quality of life for patients with metastatic melanoma. Many questions remain unanswered, however, such as what is the optimal sequencing of drugs, whether drug combinations can improve the results and whether new drugs such as PI3K/AKT/mTOR inhibitors have a place in the treatment of melanoma. This review article covers the literature regarding the use of the new drugs cited in current guidelines for the treatment of metastatic melanoma.

Key words: BRAF, Immunotherapy, Ipilimumab, Melanoma, PD-1, Vemurafenib.