title: Activity of trametinib in K601E and L597Q BRAF mutation-positive metastatic melanoma.
abstract: BRAF and MEK inhibitors are not established treatments for non-V600 mutation-positive metastatic melanoma. We carried out a retrospective analysis of efficacy and safety in four patients with BRAF K601E and one patient with L597Q mutation-positive metastatic melanoma treated with the MEK inhibitor trametinib. Three patients achieved a RECIST partial response, including the patient with an L597Q mutation. Paired biopsies available in one of the five patients showed reduced phospho-ERK signalling and this corresponded to a metabolic response on F-fluorodeoxyglucose-PET scanning. Trametinib toxicity was manageable. Trametinib has antitumour activity in patients with BRAF K601E and L597Q mutation-positive metastatic melanoma.
authors.affiliation: aDepartment of Medical Oncology, Cancer Centre, Sir Charles Gairdner Hospital bSchool of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia cPeter MacCallum Cancer Centre, East Melbourne dSir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria eMelanoma Institute Australia, North Sydney fUniversity of Sydney, Sydney, New South Wales, Australia.
authors.forename: Samantha E
authors.initials: SE
authors.lastname: Bowyer
authors.forename: Aparna D
authors.initials: AD
authors.lastname: Rao
authors.forename: Megan
authors.initials: M
authors.lastname: Lyle
authors.forename: Shahneen
authors.initials: S
authors.lastname: Sandhu
authors.forename: Georgina V
authors.initials: GV
authors.lastname: Long
authors.forename: Grant A
authors.initials: GA
authors.lastname: McArthur
authors.forename: Jeanette M
authors.initials: JM
authors.lastname: Raleigh
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Hicks
authors.forename: Michael
authors.initials: M
authors.lastname: Millward
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001706:Biopsy; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000737:chemistry; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D008545:Melanoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D049268:Positron-Emission Tomography; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D011728:Pyridones / Q000627:therapeutic use*; D011744:Pyrimidinones / Q000627:therapeutic use*; D012189:Retrospective Studies; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011728:Pyridones; D011744:Pyrimidinones; D019788:Fluorodeoxyglucose F18; C560077:trametinib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D048049:Extracellular Signal-Regulated MAP Kinases