Reference Detail

Ref Type

Journal Article

PMID

(24933606)

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.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Melanoma research	24	5	2014 Oct	504-8	Melanoma Res

URL

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.

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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