Abstract 5548: High copy number of the MET gene predicts resistance to EGFR-TKI in non-small cell lung cancer patients.

Abstract

Abstract Background Non-small cell lung cancer (NSCLC) patients with EGFR gene mutations have shown a dramatic responses to EGFR tyrosine kinase inhibitor (EGFR-TKI). However, it is recognized that, clinically, drug resistance eventually emerges and this limits the mean duration of response. Although mechanisms of acquired resistance to EGFR-TKI, such as T790M secondary mutation and MET amplification, have recently been described, other mechanisms of resistant to EGFR-TKI should be identified to broaden the therapeutic strategy for NSCLC in patients with EGFR gene mutations. Patients and Methods We evaluated 26 lung tumor samples from NSCLC patients who had received EGFR-TKI treatment from 2009 to 2011 at Nippon Medical School Hospital. Status of copy numbers and amplification of the MET gene were examined by fluorescence in situ hybridization (FISH) and estimated by high throughout automated image analysis. Results High copy number (>4 copies/cell) was observed in 6 patients (27%) and amplification (MET/CEP7 ≥2.0) was seen in 0 of 26 NSCLC patients. MET gene copy number status was not correlated with EGFR gene mutation, gender, histology, or smoking history. In 2 of the 6 cases with high copy number, high copy numbers were found at both the pre- and post-treatment stages. Among the 6 patients with high copy number, 5 patients achieved partial response (PR) and one patient showed stable disease (SD) with EGFR-TKI therapy. However, the 6 patients with high copy number had statistically significantly shorter progression-free survival (PFS) than the 20 patients with low copy numbers. (p=0.048, log-rank test). The median PFS of patients with High copy number and low copy numbers was 9.5 months and 24.4 months, respectively. Conclusion Detection of high copy number of the MET gene by FISH may be useful for predicting response to EGFR-TKI. The correlation between MET gene copy number and response to EGFR-TKI should be further evaluated using larger sample sizes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5548. doi:1538-7445.AM2012-5548