Bowyer Samantha E, Rao Aparna D, Lyle Megan, Sandhu Shahneen, Long Georgina V, McArthur Grant A, Raleigh Jeanette M, Hicks Rodney J, Millward Michael
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.
Melanoma Res. 2014 Oct;24(5):504-8. doi: 10.1097/CMR.0000000000000099.
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.
BRAF和MEK抑制剂并非非V600突变阳性转移性黑色素瘤的既定治疗方法。我们对4例BRAF K601E突变和1例L597Q突变阳性转移性黑色素瘤患者使用MEK抑制剂曲美替尼进行了疗效和安全性的回顾性分析。3例患者达到了RECIST部分缓解，包括1例L597Q突变患者。5例患者中的1例可获得的配对活检显示磷酸化ERK信号传导降低，这与F-氟脱氧葡萄糖-PET扫描的代谢反应相对应。曲美替尼的毒性是可控的。曲美替尼对BRAF K601E和L597Q突变阳性转移性黑色素瘤患者具有抗肿瘤活性。
