T790M mutation and c-MET amplification might be correlated to TTP of EGFR-TKI in NSCLC

8107 Background: In current knowledge about 50% of non-small cell lung cancer resistance to TKI is due to the occurrence of a secondary mutation in exon 20 of EGFR (T790M) and 20% to c-MET amplification. The relationship between time to progression and mutation or amplification is still unknown. This study was to investigate the difference between T790M mutation and C-MET amplification in gefitinib or erlotinib resistant NSCLC. Methods: 14 EGFR-TKI resistant NSCLC tissue samples and 23 samples without treatment of EGFR-TKI were collected. T790M mutation was detected by direct sequencing. C-MET was quantified by SYBR Green real time qPCR in cancer tissues selected by laser microdissection. Results: T790M mutation was detected in 21.4% (3/14). C-MET was highly amplificated in 15.4% (2/13). Both coexisting of T790M mutation and C-MET amplification in one sample was not detected. The median TTP in 14 cases resistant to EGFR-TKI was 210 days and overall survival 449 days. The median TTP in patients with highly amplificated C-MET was 40 days and OS 68 days. The TTP in cases with T790M mutation was 398 days and OS 680. The remaining cases with neither T790M nor C-MET were 192 and 477 days. Theses suggested that there were some relationship between TTP of TKI and resistant mutation or c-MET amplification. 100% (5/5) patients with T790M or highly amplificated c-MET were resistant to subsequent treatments (chemotherapy or irradiation) following EGFR-TKI, but 44.4% (4/9) cases achieved disease control when negative T790M or C-MET. Conclusions: T790M mutation and c-MET amplification might predict the resistance to EGFR TKI. The study implies that T790M mutation or highly amplificated C-MET is correlated to TTP of EGFR-TKI treatment in NSCLC. And the presence of T790M or highly amplificated C-MET might predict poor response to further treatment failure to EGFR-TKI. No significant financial relationships to disclose.