Abstract 1800: Analysis of <i>EGFR</i> mutations before and after EGFR-TKIs treatment
Authors: Hiroyuki Yamaguchi, Nanae Tomonaga, Takaya Ikeda, Hiroaki Senju, Daiki Ogawara, Seiji Doi, Katsumi Nakatomi, Tetsuya Iida, Yoichi Nakamura, Kazuhiro Tsukamoto, Shigeru Kohno
Journal: Cancer Research (2010)

Abstract Background: Gefitinib is the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that has the dramatically effects in selective patients with non-small cell lung cancer (NSCLC). EGFR mutations predict response and survival in patients treated with gefitinib. However, almost of these patients have a relapse within a year after the start of therapy. Although the mechanisms of acquired resistance to Gefitinib were MET amplification, L861Q and hepatocyte growth factor(HGF), main reason was a secondary EGFR mutation, threonine to methionine at codon 790 in exon 20 (T790M). Therefore, we analyzed EGFR mutations after gefitinib treatment in addition to before treatment in patients with NSCLC. Materials and methods: From December 2004 to September 2009, 37 patients with advanced NSCLC harboring EGFR mutations were treated with gefitinib in our hospital. When tumor was relapsed, we got written informed consent from patients, and re-examination of EGFR mutations was performed in 9 patients by present. EGFR mutations were examined by mutant-enriched polymerase chain reaction (PCR) method and/or peptide nucleic acid-locked nucleic acid (PNA-LNA) PCR clamp method. Samples were the paraffin-embedded specimens, transbronchial biopsied tissues, surgically resected tissues, bronchial washing liquids, and pleural effusion, and we used relapsed tumor samples at secondary analysis. In addition, we evaluated the response to treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST) and progression free survival defined as the time from the date of beginning treatment to the date of disease progression or death. Results: 37 patients treated by gefitinib, response rate was 60%(22/37) and disease control rate was 78%(29/37). Within a year, most patients were relapse. In 9 patients, we could analyze EGFR mutations again. Secondary analysis of EGFR mutations was performed in safety. T790M, a resistant mutation of EGFR, was detected in 4 patients. Samples from lymph node biopsy were used in 2 patients, pleural effusion was in a patient, and transbronchial biopsied tissue was in a patient. 1 patient was adenosquamous cell carcinoma, and all of the rest were adenocarcinoma. Despite emergence of T790M, in a patient, readministration of gefitinib was effective (stable disease), furthermore, treatment of erlotinib after gefitinib was also effective (partial response). In 1 patient, secondary analysis is performing at present. Conclusion: These results suggested the importance of EGFR analysis after relapse in patients treated with gefitinib. We must consider why erlotinib was effective in patients with T790M, and screen appropriate subjects of readministration of EGFR-TKIs. The new therapeutic strategy according to the mechanism of resistance to EGFR-TKI is expected. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1800.