Patient with EGFR-mutant lung cancer harboring de novo MET amplification successfully treated with gefitinib combined with crizotinib

Abstract

While 50% of lung adenocarcinoma patients in Asia have mutations in the epidermal growth factor receptor (EGFR) site, there are few patients with the EGFR mutation accompanied by de novo mesenchymal-epithelial transition (MET) amplification. Due to the low incidence rate, there is no consensus regarding treatment. Here, a case of a 62-year-old never smoker presented with EGFR Exon19del and de novo MET amplification. A radiographic examination and computed tomography (CT) imaging were conducted on the chest and middle abdomen. A pulmonary puncture was performed and a sample of the lung tissue was used for pathologic diagnosis. Immunohistochemistry was performed for the expression of CK, P40, P63, ttf-1, NapsinA, alk-d5f3, and ki-67 on the cancer cells. Craniocerebral magnetic resonance and whole body bone imaging were completed. Second-generation gene sequencing (next-generation sequencing [NGS]) and fluorescence in situ hybridization examination were also performed to further characterize the cancer cells. A radiographic examination was performed and revealed space-occupying lesions in the lungs. CT results revealed a mass in the upper lobe of the left lung. The pathologic diagnosis was non-small cell carcinoma T3N2M1a. Second-generation gene sequencing (NGS) indicated EGFR Exon 19del (p.E746_A750del, mutant abundance: 13.99%) with de novo MET amplification (CHR: q31.2, CN = 4.0). Fluorescence in situ hybridization examination confirmed MET amplification. Targeted therapy with gefitinib combined with crizotinib was administered as treatment. Four weeks later, the CT results revealed a substantial reduction in the lesion size. The patient was followed up with favorable complete recovery and no tumor-related symptoms. Although crizotinib is efficacious when used alone in follow-up treatment; however, these results of this case and others indicate that it is likely safe to use both drugs together in the case of drug resistance.

Keywords: De novo MET amplification; EGFR mutation; Non–small cell lung cancer; Treatment.