Case Report: Short-term response to mesenchymal epithelial transition inhibitor/epidermal growth factor receptor tyrosine kinase inhibitor combination in EGFR-mutated non-small cell lung cancer with acquired MET overexpression after progression and discussion on comprehensive management.

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is a priority and important treatment for EGFR-mutated non-small cell lung cancer (NSCLC) and significantly improves patient's survival. However, these patients eventually develop disease progression due to acquired resistance to EGFR-TKI. Mesenchymal epithelial transition (MET) gene alteration is one of the common EGFR-independent mechanisms to resist EGFR-TKI. This study reports that a case with chief complaint of dry cough for six months was diagnosed with right lung adenocarcinoma (cT4N3M1c, stage IVB). After first-generation EGFR-TKI treatment, the patient underwent disease progression. After a multi-disciplinary team (MDT) discussion, a re-biopsy and next-generation sequencing (NGS) profiling were performed again, which indicated that the patient harbored the EGFR exon21 L858R mutation and the exon20 T790M mutation. According to the MDT discussion, the patient received the third-generation EGFR-TKI treatment and stereotactic body radiation therapy (SBRT), achieving long-term survival with a high quality of life. After three years of the third-generation EGFR-TKI treatment, the disease progressed again, and a biopsy indicated multiple mutations. After disease progression during the third-generation EGFR-TKI treatment and radiotherapy, the patient received combined treatment with first-generation and the third-generation EGFR-TKI, but could not tolerate the combined treatment. After three courses of chemotherapy plus bevacizumab targeted therapy, the disease continued to progress. Without other effective treatments, the patient received dual-targeted therapy with the third-generation EGFR-TKI and MET-TKI for one month, and the patient experienced a reduction of 51.4% in the size of the lesions in the chest. Unfortunately, the patient developed a lung infection and died of a lung infection. With the assistance of MDT recommendations, the patient received comprehensive treatment and remained asymptomatic, with persistent improvement in the quality of life for 4 years. The overall survival was approximately 56.5 months. Patients with metastatic EGFR-mutated NECLC require multidisciplinary discussions and comprehensive treatment. When the disease progresses, rebiopsy and NGS profiling are required to identify sensitive targeted drugs. Whether MET overexpression is a mechanism for the resistance to third-generation EGFR-TKI in NSCLC patients with EGFR mutations remains to be further investigated.