title: BRAF plus MEK-targeted drugs: a new standard of treatment for BRAF-mutant advanced melanoma.
abstract: BRAF plus MEK-targeted drugs have out-performed BRAF inhibitor monotherapy in three randomized phase 3 studies, and such combinations have become a new standard of treatment for BRAF-mutant advanced melanoma. With an overall response rate of about 70%, no other therapy in melanoma has shown a better response rate in late-phase clinical trials than combined BRAF and MEK inhibitors; the rapid kinetics of response make them the ideal front-line treatment for symptomatic, BRAF-mutant advanced melanoma patients. Nevertheless, the development of mechanisms of resistance limits the duration of response to such treatment in the majority of cases, with only about 20% of patients treated with the combination being progression-free at 3 years. The aim of this review is to report the efficacy and safety outcomes of the combination of BRAF plus MEK inhibitors compared with BRAF inhibitor monotherapy and immunotherapy, as well as to discuss future perspectives to improve outcomes based on current clinical and translational research studies.
authors.affiliation: Department of Medical Oncology, IRCCS San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Largo R. Benzi, 10, 16132, Genoa, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Queirolo
authors.affiliation: Department of Medical Oncology, IRCCS San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Largo R. Benzi, 10, 16132, Genoa, Italy. francesco.spagnolo85@gmail.com.
authors.forename: Francesco
authors.initials: F
authors.lastname: Spagnolo
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors*; D008545:Melanoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D058990:Molecular Targeted Therapy; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020930:MAP Kinase Kinase Kinases
keywords: BRAF; Cobimetinib; Dabrafenib; MEK; Melanoma; Trametinib; Vemurafenib