REVIEW ARTICLE A Review of Novel Therapies for Melanoma Chante Karimkhani • Rene Gonzalez • Robert P. Dellavalle Published online: 14 June 2014 Ó Springer International Publishing Switzerland 2014 Abstract This review summarizes results from major recent trials regarding novel therapeutic agents in mela- noma. The topics discussed include targeted therapy with BRAF (V-RAF murine sarcoma viral oncogene homo- log B) inhibitors (vemurafenib and dabrafenib), MEK (mitogen-activated protein kinase kinase) inhibitors (tra- metinib), bcr-abl/c-kit/PDGF-R inhibitors (imatinib), and angiogenesis inhibitors (bevacizumab and aflibercept), as well as immunotherapy with anti-CTLA-4 (anti-cytotoxic T-lymphocyte antigen-4) antibodies (ipilimumab), anti-PD (anti-programmed death receptor) antibodies (nivolumab and lambrolizumab), and anti-PD-L (anti-programmed death ligand) antibodies. Various combinations of these agents, as well as adjunctive GM-CSF (granulocyte–mac- rophage colony-stimulating factor), T-VEC (talimogene laherparepvec) oncolytic viruses, and novel chemothera- peutic agents, are also described. Despite the tremendous advances that these novel treatments have created, optimal therapeutic agent selection remains a highly individualized decision. Melanoma therapy has vastly progressed since the days when dacarbazine was the sole option for advanced melanoma patients. The molecular understanding of melanoma pathogenesis has yielded a brighter future for advanced melanoma patients. Key Points Novel melanoma therapy includes targeted agents, immunotherapy, and various combinations of agents within these classes Unique mechanisms of new therapeutic agents require modified response criteria to properly assess tumor response Ongoing studies and numerous clinical trials are investigating combinations of agents that may improve response and survival rates and may delay resistance 1 Introduction Although melanoma accounts for less than 5 % of all skin cancers, it is the most deadly because of its propensity for metastatic spread throughout the body. Incidence rates for melanoma in the USA have been increasing over the past 30 years, with an estimated 2013 incidence of 76,690 new melanoma diagnoses and 9,480 deaths. Approximately 1 in 50 persons in the USA will be diagnosed with C. Karimkhani Columbia University College of Physicians and Surgeons, New York, NY, USA R. Gonzalez University of Colorado Cancer Center, Aurora, CO, USA R. P. Dellavalle Department of Dermatology, University of Colorado Denver, Aurora, CO, USA R. P. Dellavalle Department of Epidemiology, Colorado School of Public Health, Aurora, CO, USA R. P. Dellavalle (&) Dermatology Service, Department of Veterans Affairs Medical Center, 1055 Clermont Street, Box 165, Denver, CO 80220, USA e-mail: robert.dellavalle@ucdenver.edu Am J Clin Dermatol (2014) 15:323–337 DOI 10.1007/s40257-014-0083-7