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

Bowyer, Samantha E.a,*; Rao, Aparna D.c,*; Lyle, Megane; Sandhu, Shahneenc; Long, Georgina V.e,f; McArthur, Grant A.c,d; Raleigh, Jeanette M.c; Hicks, Rodney J.c,d; Millward, Michaela,b

doi: 10.1097/CMR.0000000000000099
Short Communications

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.

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

* Samantha E. Bowyer and Aparna D. Rao contributed equally to the writing of this article.

Correspondence to Michael Millward, MBBS, MA, FRACP, Department of Medical Oncology, Cancer Centre, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, Western Australia 6009, Australia Tel: +61 893 462 098; fax: +61 893 462 816; e-mail: michael.millward@uwa.edu.au

Received May 5, 2014

Accepted May 12, 2014

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins