title: New developments in the treatment of metastatic melanoma: immune checkpoint inhibitors and targeted therapies.
abstract: The incidence of melanoma has been increasing over the past twenty years. Unfortunately, the prognosis of advanced-stage disease is still poor. Advances have been made in the understanding of melanoma development and progression, resulting in the availability of promising novel therapeutic options. After the approval of ipilimumab, an immune checkpoint inhibitor of cytotoxic T-lymphocyte-associated antigen-4, and vemurafenib, a targeted v-raf murine sarcoma viral oncogene homolog B1 inhibitor, a new era for melanoma has started. Additional compounds, such as dabrafenib and trametinib, also received Food and Drug Administration approval recently and currently several other promising candidates, such as antibodies to programmed death-1, are under clinical development. Even though the novel compounds show impressive results as monotherapy, their efficacy may be enhanced in combination with other agents. In addition, combined treatment may reduce the chance of developing resistance. We review available clinical experience on approved therapies and discuss new developments. Furthermore, promising combination therapies are highlighted.
authors.affiliation: Department of Medical Oncology, VU University Medical Center, CCA 1.42, PO Box 7057,1007 MB Amsterdam, the Netherlands. Gj.peters@vumc.nl.
authors.forename: Kaamar
authors.initials: K
authors.lastname: Azijli
authors.forename: Ellen
authors.initials: E
authors.lastname: Stelloo
authors.forename: Godefridus J
authors.initials: GJ
authors.lastname: Peters
authors.forename: Alfons J M
authors.initials: AJ
authors.lastname: VAN DEN Eertwegh
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D007167:Immunotherapy; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D007155:Immunologic Factors; D047428:Protein Kinase Inhibitors; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; CTLA-4; Melanoma; PD1; ipilimumab; vemurafenib