Clinical outcomes of <i><scp>EGFR</scp></i>+/<scp><i>MET</i>amp</scp>+ vs. <scp><i>EGFR</i></scp>+/<scp><i>MET</i>amp</scp>‐ untreated patients with advanced non‐small cell lung cancer
Kai‐Cheng Peng, Junwei Su, Zhi Xie, Han‐Min Wang, Mei‐Mei Fang, Wenfeng Li, Yuqing Chen, Xuhui Guan, Jian Su, Hong‐Hong Yan, Xu‐Chao Zhang, Hai‐Yan Tu, Qing Zhou, Hua‐Jun Chen, Yi‐Long Wu, Jin‐Ji Yang
Abstract
BACKGROUND: MET dysregulation has been implicated in the development of primary and secondary resistance to EGFR tyrosine kinase inhibitor (TKI) therapy. However, the clinicopathological characteristics and outcomes of patients harboring EGFR-sensitive mutations and de novo MET amplifications still need to be explored. METHODS: A total of 54 patients from our hospital with non-small cell lung cancer harboring EGFR-sensitive mutations and/or de novo MET amplifications were included in this study. Survival rates were estimated by the Kaplan-Meier method with log-rank statistics. Lung cancer organoids (LCOs) were generated from patient-derived malignant pleural effusion to perform drug sensitivity assays. RESULTS: Fifty-four patients with the appropriate clinicopathological characteristics were enrolled. MET FISH was performed in 40 patients who were stratified accordingly into two groups: EGFR+/METamp- (n = 22) and EGFR+/METamp + (n = 18). Survival rates for EGFR+/METamp- and EGFR+/METamp + patients respectively, were as follows: the median progression-free survival (PFS) was 12.1 and 1.9 months (p<0.001); the median post-progression overall survival (pOS) was 25.6 and 11.6 months (p = 0.023); the median overall survival (OS) was 33.2 and 12.7 months (p = 0.013). Drug testing conducted in LCOs derived from malignant pleural effusion from EGFR+/METamp + patients showed that dual targeted therapy was more effective than TKI monotherapy. CONCLUSION: EGFR+/METamp + patients treated with first-line TKI monotherapy had poor clinical outcomes. Dual targeted therapy showed potent anticancer activity in the LCO drug testing assay, suggesting that it is a promising first-line treatment for EGFR+/METamp + patients. Randomized controlled trials are needed to further validate these results.