Treatment for Advanced Melanoma: New Drugs, New Opportunities, New Challenges

摘要

The standard of care for the treatment of patients with metastatic melanoma has changed fundamentally based on two new treatment strategies that are, conceptually and biologically, largely independent: the blockade of immune regulatory molecules with monoclonal antibodies (termed "immune checkpoint blockade") and the inhibition of BRAF V600 mutation-driven mitogen-activated protein kinase (MAPK) signaling using small-molecule kinase inhibitors. Based on improved overall survival documented in phase III trials, the monoclonal antibody ipilimumab (Yervoy) and the tyrosine kinase inhibitor vemurafenib (Zelboraf) received regulatory approval, providing accessible opportunities for patients. [1,2] While the previously established treatments, such as chemotherapy with dacarbazine, biochemotherapy, high-dose interleukin 2 (IL-2), and adoptive T-cell transfer, remain in the therapeutic armamentarium of the clinician treating patients with advanced melanoma, ipilimumab and vemurafenib have become primary treatment modalities due to their proven survival benefits.