Current Situation Investigation of Clinical Diagnosis and Treatment of Non-Small Cell Lung Cancer With MET Alterations in China

Objective Mesenchymal epithelial transition (MET) factor alteration in non-small cell lung cancer (NSCLC) mainly includes MET exon 14 skipping alteration (METex14 skipping), MET gene amplification, and MET protein overexpression, etc. METex14 skipping is a driver gene mutation in advanced NSCLC, and the incidence of METex14 skipping in NSCLC patients was 0.9%~4%. Currently, several drugs targeting METex14 skipping have been approved in China and other countries. The incidence of de novo MET gene amplification in NSCLC patients was 1%~5%, which was associated with poor prognosis. MET gene amplification is more frequently occurring after targeted therapy in NSCLC patients with other positive driver genes and is one of the important mechanisms of EGFR-TKI resistance. The purpose of this study is to understand the status of diagnosis and treatment of NSCLC patients with MET alterations in China, including awareness of physicians on MET inhibitors, considerations for treatment decisions of NSCLC patients with MET alterations, and to explore the unmet needs in clinical practice.

Method Physicians who had treated MET alteration patients within a defined period participated in the survey through the online questionnaire, and the results were summarized and descriptively analyzed.

Results A total of 140 valid questionnaires were collected. For METex14 skipping NSCLC, MET-TKI monotherapy was preferred by more than 50% of the physicians interviewed, regardless of whether patients were treatment naïve or pretreated. The incidence of grade ≥3 adverse events (AE) was the most concerned safety indicator, and the most concerned AEs included pneumonia, hepatotoxicity, and gastrointestinal AEs, etc. Peripheral edema caused by MET-TKI was of low concern. For MET-amplified EGFR mutant (EGFRm) NSCLC after EGFR-TKI resistance, the interviewed physicians preferred MET-TKI and EGFR-TKI dual-targeted combination therapy. More sufficient evidence from large-scale randomized controlled studies, standardized testing, and clinical consensus were the major unmet needs for MET-amplified EGFRm NSCLC after EGFR-TKI resistance.

Conclusions The preferred proportion of MET-TKI therapy in METex14 skipping NSCLC remains to be improved, and more attention should be paid to MET-TKI-induced peripheral edema to help better management. Testing for different types of MET alteration requires further standardization and normalization.