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|Ref Type||Journal Article|
|Authors||Bowyer SE, Rao AD, Lyle M, Sandhu S, Long GV, McArthur GA, Raleigh JM, Hicks RJ, Millward M|
|Title||Activity of trametinib in K601E and L597Q BRAF mutation-positive metastatic melanoma.|
|Abstract Text||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.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|BRAF L597Q||melanoma||predicted - sensitive||Trametinib||Case Reports/Case Series||Actionable||In a retrospective analysis, first-line treatment with Mekinist (trametinib) resulted in a partial response lasting 6.2 months in a melanoma patient harboring BRAF L597Q, with 33% tumor shrinkage (PMID: 24933606).||24933606|
|BRAF K601E||melanoma||predicted - sensitive||Trametinib||Case Reports/Case Series||Actionable||In a retrospective analysis, treatment with Mekinist (trametinib) resulted in a clinical benefit rate of 75% (3/4) in melanoma patients harboring BRAF K601E, with two partial responses each lasting 2.5 and 5.5 months, and one with stable disease lasting 3.6 months with a 27% reduction in tumor mass (PMID: 24933606).||24933606|