Clinical response to crizotinib and emergence of resistance in lung adenocarcinoma harboring a MET c-Cbl binding site mutation.

Abstract

OBJECTIVES\nMET c-Cbl binding site mutations constitute about 2 % of MET exon 14 alterations in lung cancer. Preclinical data suggests regarding these mutations as functional analogs of MET exon 14 skipping mutations, but clinical validation is lacking.\n\n\nRESULTS\nWe report the case of a patient with metastastic lung adenocarcinoma harboring a c-Cbl binding site alteration and demonstrate clinical, radiological and metabolic response to crizotinib with a PFS of 10.6 months. As escape mechanism, a typical MET resistance mutation could be identified.\n\n\nCONCLUSION\nMET c-Cbl binding site mutations should be regarded as a distinct subtype of MET exon 14 alterations. Patients with lung cancer harboring such mutations should be offered targeted therapy.