BIM and SHP2 expression levels to predict clinical outcome to EGFR tyrosine kinase inhibitors (TKI) in EGFR-mutant non-small-cell lung cancer (NSCLC) patients (p).

Abstract

e19078 Background: EGFR mutations are among the most common driver mutations, responding well, albeit transiently, to EGFR TKIs. We were able to identify high levels of BIM mRNA expression as a predictive marker of response, progression free survival (PFS) and overall survival (OS) in erlotinib-treated NSCLC p. The Src-homology 2 domain-containing phosphatase 2 (SHP2), encoded by PTPN11, is downstream of both EGFR and several other receptor tyrosine kinases (RTK). SHP2 is required for sustained activation of extracellular signal-regulated kinase (ERK) and BIM downregulation. Methods: We assessed the static levels of BIM and SHP2 mRNA expression, by quantitative real time polymerase chain reaction, and correlated our findings with PFS and OS in 30 EGFR-mutant NSCLC p treated with EGFR TKIs like erlotinib, gefitinib or afatinib. Results: Median age 68; 73.3% female; 73.3% never-smokers; 83.3% adenocarcinoma; 80% erlotinib treated; 66.7% response rate to EGFR TKIs. PFS was 22.3 months (m) for p with intermed...