title: Treatment algorithms in stage IV melanoma.
abstract: The molecular classification of melanoma and the advent of new drugs are changing the paradigm of therapy for advanced melanoma. A review of the recent key studies was performed, followed by a discussion in an expert forum. The aim of this review was to generate a therapeutic algorithm for stage IV melanoma. Tumor genotyping for BRAF and/or KIT should be performed before selection of therapy. For most BRAF-mutated melanoma patients and particularly those with a high tumor load, vemurafenib or other BRAF inhibitors such as dabrafenib are the treatment of choice. KIT inhibitors can be effective in KIT-mutant tumors, especially in those patients with mutations at exons 11 and 13. Ipilimumab is a good option for patients with nontargetable or nondetected mutations and those who progress under therapy with vemurafenib or a KIT inhibitor. There is still a role for conventional chemotherapy either as first-line treatment in BRAF wild-type patients or as salvage therapy in second or third line, or after other treatment modalities. Participation in clinical trials is strongly encouraged, either in first or in subsequent lines. New therapeutic options for advanced melanoma are guided by tumor genotyping. The current therapeutic algorithm includes kinase inhibitors, anti-CTLA4 therapy, immunotherapy, and chemotherapy, depending on the tumor genotype and response to previous treatments. Participation in clinical trials should always be encouraged because the treatment goal is long-term survival and potential cure in a subset of patients.
authors.affiliation: 1Service of Oncology, Hospital La Paz, Madrid, Spain; 2Department of Dermatology, Hopital Ste Marguerite, Marseille, France; 3Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland; 4Department of Sarcoma and Melanoma, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland; 5Department of Dermatology (CR), and General Director (AE), Institute Gustave Roussy, Villejuif Cedex, France; 6First Department of Medicine, University of Athens Medical School, Athens, Greece; 7Department of Oncology, Westmead Hospital and Melanoma Institute Australia, University of Sydney, Sydney, Australia; 8Service of Oncology, Clinica Universitaria de Navarra, Pamplona, Spain; 9Department of Dermatology, University of Kiel, Kiel, Germany; and 10Department of Dermatology, University Hospital Essen, Essen, Germany.
authors.forename: Enrique
authors.initials: E
authors.lastname: Espinosa
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Grob
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dummer
authors.forename: Piotr
authors.initials: P
authors.lastname: Rutkowski
authors.forename: Caroline
authors.initials: C
authors.lastname: Robert
authors.forename: Helen
authors.initials: H
authors.lastname: Gogas
authors.forename: Richard
authors.initials: R
authors.lastname: Kefford
authors.forename: Alexander M M
authors.initials: AM
authors.lastname: Eggermont
authors.forename: Salvador
authors.initials: S
authors.lastname: Martin Algarra
authors.forename: Axel
authors.initials: A
authors.lastname: Hauschild
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
mesh_terms: D000465:Algorithms; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000379:methods; D015195:Drug Design; D005838:Genotype; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents