Activity of trametinib in K601E and L597Q BRAF mutation-positive metastatic melanoma

S.E. Bowyer; A.D. Rao; M. Lyle; S. Sandhu; G. Long; G.A. Mcarthur; J.M. Raleigh; R.J. Hicks; Michael Millward

doi:10.1097/CMR.0000000000000099

Activity of trametinib in K601E and L597Q BRAF mutation-positive metastatic melanoma

S.E. Bowyer
, A.D. Rao
, M. Lyle
, S. Sandhu
, G. Long
, G.A. Mcarthur
, J.M. Raleigh
, R.J. Hicks
, Michael Millward

Research output: Contribution to journal › Article › peer-review

67 Citations (Web of Science)

Abstract

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. 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 18F-fluorodeoxyglucose-PET scanning. Trametinib toxicity was manageable. Trametinib has antitumour activity in patients with BRAF K601E and L597Q mutation-positive metastatic melanoma.

Original language	English
Pages (from-to)	504-508
Journal	Melanoma Research
Volume	24
Issue number	5
DOIs	https://doi.org/10.1097/CMR.0000000000000099
Publication status	Published - 2014

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title = "Activity of trametinib in K601E and L597Q BRAF mutation-positive metastatic melanoma",

abstract = "{\textcopyright} 2014 Wolters Kluwer Health | Lippincott Williams \& Wilkins. 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 18F-fluorodeoxyglucose-PET scanning. Trametinib toxicity was manageable. Trametinib has antitumour activity in patients with BRAF K601E and L597Q mutation-positive metastatic melanoma.",

author = "S.E. Bowyer and A.D. Rao and M. Lyle and S. Sandhu and G. Long and G.A. Mcarthur and J.M. Raleigh and R.J. Hicks and Michael Millward",

year = "2014",

doi = "10.1097/CMR.0000000000000099",

language = "English",

volume = "24",

pages = "504--508",

journal = "Melanoma Research",

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publisher = "Lippincott Williams \& Wilkins",

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}

TY - JOUR

T1 - Activity of trametinib in K601E and L597Q BRAF mutation-positive metastatic melanoma

AU - Bowyer, S.E.

AU - Rao, A.D.

AU - Lyle, M.

AU - Sandhu, S.

AU - Long, G.

AU - Mcarthur, G.A.

AU - Raleigh, J.M.

AU - Hicks, R.J.

AU - Millward, Michael

PY - 2014

Y1 - 2014

N2 - © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. 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 18F-fluorodeoxyglucose-PET scanning. Trametinib toxicity was manageable. Trametinib has antitumour activity in patients with BRAF K601E and L597Q mutation-positive metastatic melanoma.

AB - © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. 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 18F-fluorodeoxyglucose-PET scanning. Trametinib toxicity was manageable. Trametinib has antitumour activity in patients with BRAF K601E and L597Q mutation-positive metastatic melanoma.

U2 - 10.1097/CMR.0000000000000099

DO - 10.1097/CMR.0000000000000099

M3 - Article

SN - 0960-8931

VL - 24

SP - 504

EP - 508

JO - Melanoma Research

JF - Melanoma Research

IS - 5

ER -

Activity of trametinib in K601E and L597Q BRAF mutation-positive metastatic melanoma

Abstract

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