De Novo MET Amplification in Chinese Patients With Non–Small-Cell Lung Cancer and Treatment Efficacy With Crizotinib: A Multicenter Retrospective Study

Abstract Background De novo mesenchymal–epithelial transition (MET) amplification represents an uncommon oncogenic event in patients with non–small-cell lung cancer, and little is known about the clinicopathologic characteristics, treatment, and prognosis of these patients. Patients and Methods Patient data were retrospectively collected in 5 hospitals in China from 2014 to 2016. All MET amplification was identified with fluorescence in-situ hybridization. A MET/centromere ratio (MET/CEN) of ≥ 1.8 was defined as positive for MET amplification. Results Amplification of the de novo MET gene was identified in 47 patients with lung cancer. Thirty-two patients had a MET/CEN > 5, while 12 patients had intermediate-level amplification and only 3 had low-level amplification. Nine of 40 patients with advanced stage disease had brain metastases, and 15 had a solid predominant subtype of adenocarcinoma. Fifteen patients were treated with crizotinib. Of these, 11 patients (73.3%) had a partial response, 3 (20%) stable disease, and 1 (6.7%) progressive disease. The median progression-free survival of the 15 patients treated with crizotinib was 6.5 months (95% confidence interval, 2.7–10.3). Notably, treatment efficacy was more pronounced in patients with high-level MET amplification than in those with intermediate-level amplification (8.6 vs. 4.4 months, P  = .008). The overall survival of patients with and without crizotinib treatment was 31.0 and 13.7 months, respectively ( P  = .001). Conclusion We observed a trend toward a high prevalence of the solid predominant subtype of adenocarcinoma and of brain metastases in this group of patients. Patients with de novo MET amplification benefit from crizotinib treatment, especially those with high-level amplification.