Osimertinib has efficacy superior to that of standard
epidermal growth factor receptor (EGFR)-
tyrosine kinase inhibitors (TKIs) for the first-line treatment of patients with EGFR-mutant advanced
non-small cell lung cancer (NSCLC). However, patients treated with
osimertinib eventually acquire drug resistance. MET missense mutations have been demonstrated to mediate resistance to MET-TKIs, such as
crizotinib. But the role of MET missense mutations in mediating EGFR TKI resistance is undefined. With the increasing use of next-generation sequencing (NGS) at diagnosis, many mechanisms of acquired resistance have been discovered in patients with activated
tyrosine kinase receptors. Herein, we report the first case of MET D1228N mutation mediating acquired resistance to
osimertinib in a MET TKI-naïve NSCLC. The patient with advanced
lung adenocarcinoma harboring EGFR exon 19 deletion initially responded to
osimertinib with progression-free survival (PFS) lasting 11 months and then developed resistance with an acquired mutation of MET D1228N. Subsequently, combination
therapy of
cabozantinib and
osimertinib was administrated to the patient, and her clinical symptoms were rapidly relieved within one week with good tolerance. She remained on the combined treatment for 10 months. Finally, she achieved an overall survival (OS) of 25 months. Based on our findings, patient with MET D1228N mutant
lung adenocarcinoma clinically benefited from combinatorial
therapy of
cabozantinib and
osimertinib after
osimertinib resistance.