Mutation tracking of a patient with EGFR-mutant lung cancer harboring de novo MET amplification: Successful treatment with gefitinib and crizotinib

Abstract

Objective: De novo mesenchymal-epithelial transition (MET) amplification is believed to promote primary resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in the non-squamous non-small cell lung cancer (NSCLC). We sought to seek the treatment of a patient with EGFR-mutant NSCLC harboring de novo MET amplification.

Materials and methods: After clinical diagnosis, tissue and plasma samples were obtained from the patient and subjected to next-generation sequencing to identify and dynamic monitor the mutations.

Results: The patient was treated with gefitinib monotherapy in the beginning and experienced primary resistance to gefitinib but achieved a good response to the combination therapy of gefitinib and crizotinib. He achieved a 16.8-month progress free survival with the combination therapy. NGS of plasma circulating cell-free tumor DNA shown that L858R mutation was no longer detectable and the copy number of MET dropped when the patient got remission.

Conclusions: The combination of EGFR- and MET- tyrosine kinase inhibitors may be an effective treatment for the rare mutations.

Keywords: De novo MET amplification; Dynamic monitoring; EGFR mutant; Non-small cell lung cancer.