Abstract 2773: A prospective observational study evaluating c-MET expression and EGFR gene mutation correlation with erlotinib response in second line treatment for advanced/metastatic non-small cell lung cancer patients
Authors: Cheol-Kyu Park, Yoo-Duk Choi, In-Jae Oh, Jung-Eun Lee, Shin Yup Lee, Tae-Won Jang, Jeong-Seon Ryu, Young-Chul Kim
Journal: Cancer Research (2017)

Abstract Background: The c-MET is associated with tumor progression and acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). The aim of this study was to evaluate the prevalence and predictive role of c-MET and EGFR mutation in non-small cell lung cancer (NSCLC). Methods: This was a multicenter prospective observational study for patients with stage IV or recurrent NSCLC who had progressive disease after 1st line chemotherapy and was followed by erlotinib for 2nd line treatment from September 2011 to September 2014. The primary outcome was to measure the rates of c-MET expression/amplification and EGFR mutation in tumor tissue. MET expression was evaluated by immunohistochemistry (IHC) and gene copy number was assessed by silver in situ hybridization (SISH). EGFR mutations were analyzed by Cobas™ version 1. Results: A total of 196 patients were enrolled and major histologic types were adenocarcinoma (67%). c-MET was overexpressed (MET IHC-positive) in 44.4% of the patients and dominant in female and non-squamous histology. c-MET amplification and high polysomy (MET SISH-positive) were observed in 1.5% and 8.7%, but there was no specific clinical characteristics. The detection rate of EGFR mutation was 10.2% (19 deletion: 11, L858R: 7, exon 20 insertion: 2 cases). The response rate of erlotinib was significantly higher in EGFR sensitive mutant group (55% vs. 4%, p&amp;lt;0.001) and the median progression-free survival (PFS) was significantly longer than wild type (173 vs 58 days, p&amp;lt;0.001). c-MET positivity (IHC- or SISH-positive) did not show significant correlation with response or PFS. Patients with SISH-positive for c-MET tended to have shorter overall survival (OS) than patients with SISH-negative (127 vs 303 days, p=0.051). Conclusion: In this observational study with 2nd line erlotinib treatment, we reconfirmed EGFR mutation is strong predictive marker, and EGFR-TKI use in EGFR wild-type patients should be considered carefully and may be harmful. c-MET overexpression was related to some clinical characteristics such as female and non-squamous histology. Although c-MET positivity was not associated with response or PFS, c-MET SISH may be predictive marker for OS. Citation Format: Cheol-Kyu Park, Yoo-Duk Choi, In-Jae Oh, Jung-Eun Lee, Shin Yup Lee, Tae-Won Jang, Jeong-Seon Ryu, Young-Chul Kim. A prospective observational study evaluating c-MET expression and EGFR gene mutation correlation with erlotinib response in second line treatment for advanced/metastatic non-small cell lung cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2773. doi:10.1158/1538-7445.AM2017-2773