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.
MeSH terms
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Aged
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Antineoplastic Agents / therapeutic use
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Biopsy
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Female
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Fluorodeoxyglucose F18 / chemistry
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Humans
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MAP Kinase Signaling System
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Male
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Melanoma / diagnostic imaging
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Melanoma / drug therapy*
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Melanoma / genetics*
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Middle Aged
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Mutation
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Neoplasm Metastasis
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Phosphorylation
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Positron-Emission Tomography
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Proto-Oncogene Proteins B-raf / genetics*
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Pyridones / therapeutic use*
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Pyrimidinones / therapeutic use*
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Retrospective Studies
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Signal Transduction
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Skin Neoplasms / diagnostic imaging
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Skin Neoplasms / drug therapy*
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Skin Neoplasms / genetics*
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Treatment Outcome
Substances
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Antineoplastic Agents
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Pyridones
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Pyrimidinones
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Fluorodeoxyglucose F18
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trametinib
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BRAF protein, human
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Proto-Oncogene Proteins B-raf
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Extracellular Signal-Regulated MAP Kinases