Analysis of the EGFR mutations in non-small cell lung cancer patients after EGFR-TKI treatment.

Abstract

e18065 Background: Gefitinib and erlotinib are the epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) that have the dramatically effects in selective patients with non-small cell lung cancer (NSCLC). EGFR mutations predict response and survival in patients treated with TKIs. However, most patients have a relapse within 1 year after the initiation of therapy. The most important mechanism of resistance to TKIs is a secondary EGFR mutation, threonine to methionine at codon 790 in exon 20 (T790M). Therefore, we analyzed EGFR mutations after TKIs treatment in addition to before treatment. Methods: 99 patients were analyzed mutation status between July 2004 to December 2009 in our institution. 71 patients were treated with TKIs (gefitinib 67 cases, erlotinib 9 cases), and mutations were detected in 31 patients. When tumor was relapsed, we got written informed consent, and re-examination of mutations was performed. Mutations were examined by mutant-enriched polymerase chain reaction method and/or peptide nucleic acid-locked nucleic acid (PNA-LNA) PCR clamp method. Samples were 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 and progression-free survival. Results: 31 patients with NSCLC harboring mutations treated with TKIs. Response rate was 74.2% (23/31). Within 1 year, most patients were relapse (83.9%, median 149 days). In 10 patients, we could analyze mutations after TKIs treatment. T790M was detected in 4 patients, and EGFR status was maintained in 6 patients. In 2 of 6 patients without T790M, readministration of gefitinib was effective, and 1 of 6 patients responded to erlotinib. Despite emergence of T790M, readministration of gefitinib and switch to erlotinib was effective in 1 patient. Conclusions: These results suggested that we cannot decide next treatment after relapse to TKIs by reason of only T790M. We must consider the mechanism of resistance to TKIs and the new therapeutic strategy. No significant financial relationships to disclose.