MET overexpression coexisting with epidermal growth factor receptor mutation influence clinical efficacy of EGFR-tyrosine kinase inhibitors in lung adenocarcinoma patients

Lihong Ma, Zhengbo Song, Yong Song, Yiping Zhang


Background: MET overexpression in non-small cell lung cancer (NSCLC) is known to be associated with unfavorable survival. We investigated the MET overexpression in epidermal growth factor receptor (EGFR)-mutated NSCLC and further to observe its value to the efficacy of patients treated with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs).
Methods: Consecutive lung adenocarcinoma patients were screened by immunohistochemistry (IHC) for the presence of MET overexpression with concurrent EGFR mutation from January 2013 to July 2015. MET positivity was defined as strong staining intensity (grade 3+) in >50% tumor cells with moderate staining (2+). EGFR mutations were confirmed by amplification refractory mutation system (ARMS). Progression-free survival (PFS) and overall survival (OS) were evaluated by Kaplan-Meier method and compared with log-rank tests.
Results: Among 167 EGFR-TKIs-treated patients, the frequency of MET overexpression was 34.1% (57/167). No difference in MET overexpression was observed among EGFR mutation type, age, gender or smoking status. The median PFS of all patients was 10.8 months and the objective response was 68.9%. Significant difference in response rate existed between MET positive and negative patients (73.6% vs. 59.6%, P=0.06). And a shorter PFS was observed for EGFR-TKIs treatment in MET-positive group than MET-negative group (10.9 vs. 10.6 months, P=0.027).
Conclusions: Concurrent MET overexpression occurred in approximately 30% EGFR-mutant patients. MET overexpression was associated with an inferior efficacy of EGFR-TKI.