Response to Crizotinib in a Patient With Lung Adenocarcinoma Harboring a MET Splice Site Mutation

Lung adenocarcinoma has been increasingly subdivided based on the presence of certain driver oncogenes that confer susceptibility to targeted therapy. Similar to ALK and ROS1 rearranged lung adenocarcinomas, those that harbor MET amplification were recently found to respond to the multitargeted tyrosine kinase inhibitor crizotinib. We describe clinical activity of crizotinib in a patient with lung adenocarcinoma with a MET splice site mutation. Although these mutations occur at nearly twice the frequency of MET amplification, special attention is required to detect them on clinical next-generation sequencing platforms. Our findings suggest the need to expand efforts to identify these mutations and evaluate responsiveness to c-Met inhibition in genotype-directed clinical trials. (C) 2015 Elsevier Inc. All rights reserved.