MET inhibitors in advanced non-small-cell lung cancer: a meta-analysis and review

The alterations of MET have been detected in non-small-cell lung cancer (NSCLC). However, survival benefit of MET inhibitors remains controversial. We performed this meta-analysis to evaluate the survival benefit of MET inhibitors combined with an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) or standard chemotherapy in patients with advanced or metastatic NSCLC. A systematic computerized search of the electronic databases was carried out. From seven studies, 2,577 patients were included in the meta-analysis. Compared with patients in the placebo group, patients who received an additional MET inhibitor did not show significantly improved progression-free survival (hazard ration (HR) = 0.92 [ 95% confidence interval (CI): 0.79-1.08], P = 0.33) and overall survival (HR = 1.0 [95% CI: 0.90-1.11], P = 0.97). In the subgroup analysis, patients with MET-high NSCLC tended to show longer survival when treated with an additional MET inhibitor than those in the placebo group (HR = 0.76, [95% CI: 0.58-1.01], P = 0.06). In conclusion, this meta-analysis indicates that the addition of a MET inhibitor to an EGFR TKI or chemotherapy has no survival benefit over placebo in patients with advanced or metastatic NSCLC. Although patients with MET-high tumor tended to show better survival, further studies to explore more specific biomarkers are warranted to identify ideal candidates for MET inhibitors in NSCLC.