title: Dabrafenib in combination with trametinib for the treatment of metastatic melanoma.
abstract: Oncogenic BRAF mutations are present in approximately 40-50% of patients with metastatic melanoma. Targeting BRAF mutations with either small molecule inhibitors of BRAF or one of the downstream mediators of oncogenic BRAF - MEK - is associated with improved outcomes compared with chemotherapy and has led to the US FDA approval of two BRAF inhibitors - vemurafenib and dabrafenib - and the MEK inhibitor trametinib. Further, the combination of dabrafenib and trametinib is well tolerated and associated with higher responses and improved survival compared with single-agent BRAF inhibitors.
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Awad
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Sullivan
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D008545:Melanoma / Q000188:drug therapy*; D010091:Oximes / Q000008:administration & dosage; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011728:Pyridones / Q000008:administration & dosage; D011744:Pyrimidinones / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic
chemical_list: D007093:Imidazoles; D010091:Oximes; D047428:Protein Kinase Inhibitors; D011728:Pyridones; D011744:Pyrimidinones; C560077:trametinib; C561627:dabrafenib
keywords: BRAF; MEK; melanoma; resistance; targeted therapy