Treatment algorithms in stage IV melanoma
Espinosa E (1), Grob JJ, Dummer R, Rutkowski P, Robert C, Gogas H, Kefford R, Eggermont AM, Martin Algarra S, Hauschild A, Schadendorf D.
(1) Service of Oncology, Hospital La Paz, Madrid, Spain; (2) Department of Dermatology, Hopital Ste Marguerite, Marseille, France; (3) Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland; (4) Department of Sarcoma and Melanoma, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland; (5) Department of Dermatology (CR), and General Director (AE), Institute Gustave Roussy, Villejuif Cedex, France; (6) First Department of Medicine, University of Athens Medical School, Athens, Greece; (7) Department of Oncology, Westmead Hospital and Melanoma Institute Australia, University of Sydney, Sydney, Australia; (8) Service of Oncology, Clinica Universitaria de Navarra, Pamplona, Spain; (9) Department of Dermatology, University of Kiel, Kiel, Germany; and (10) Department of Dermatology, University Hospital Essen, Essen, Germany.
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.
CITATION Am J Ther. 2015 Jan-Feb;22(1):61-7. doi: 10.1097/MJT.0b013e31829e885c.