C-MET overexpression as a resistance biomarker to epidermal growth factor receptor tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer.

e20660 Background: Multiple mechanisms of C-MET activation have been reported in non-small cell lung cancer (NSCLC) including amplification and mutation. C-MET protein overexpression also occurs in 25%-75% of NSCLC and is associated with poor prognosis of NSCLC. This study aimed to evaluate whether C-MET protein expression is associated with the efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) in EGFR-mutant NSCLC. Methods: We retrospectively analyzed 1199 consecutive NSCLC patients, who were tested for C-MET expression by immunohistochemistry (IHC) between Nov 2013 and Sep 2015. The staining intensity within tumor tissue was graded on a scale of 0 (negative), 1+ (weak), 2+ (moderate), and 3+ (strong). C-MET positivity was defined as C-MET expression with strong staining intensity (grade 3+) in more than 50% of tumor cells. Among 262 patients with EGFR exon 19 deletions or exon 21 L858R mutation, 83 EGFR-mutant patients received EGFR-TKI as a first line therapy. Results: In total of 1199 tumors, the frequency of each tumor with C-MET grade 0 to grade 3+ was 10.8%, 41.0%, 32.5%, and 15.7%, respectively. C-MET expression was significantly stronger in the tumors with adenocarcinoma than those with squamous cell carcinoma (P< 0.001). In the tumors with adenocarcinoma, EGFR-mutant tumors showed stronger expression of C-MET than EGFR-wild type tumors (P< 0.001) but no difference in C-MET expression by mutation types was observed (P= 0.248). In the first-line EGFR-TKI treatment group, there was no significant difference in response rate to EGFR-TKI between the patients with C-MET positivity (n = 7) and those with C-MET negativity (n = 76) (71% vs. 88%, P= 0.231). However, the median progression-free survival (PFS) to EGFR-TKI was significantly shorter in the C-MET positive group compared with the C-MET negative group (4.3 months vs. 11.9 months, P= 0.015). Conclusions: C-MET overexpression was associated with shorter PFS to EGFR-TKI in the patients with EGFR-mutant NSCLC. C-MET overexpression might be as a biomarker to resistance to EGFR-TKI therapy in this population.