De novo resistance to epidermal growth factor receptor-tyrosine kinase inhibitors in EGFR mutation-positive patients with non-small cell lung cancer

Masayuki Takeda, Isamu Okamoto, Yoshihiko Fujita, Tokuzo Arao, Hiroyuki Ito, Masahiro Fukuoka, Kazuto Nishio, Kazuhiko Nakagawa

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Background: Somatic mutations in the epidermal growth factor receptor (EGFR) gene are a predictor of response to treatment with EGFR tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). However, mechanisms of de novo resistance to these drugs in patients harboring EGFR mutations have remained unclear. We examined whether the mutational status of KRAS might be associated with primary resistance to EGFR-TKIs in EGFR mutation-positive patients with NSCLC. Methods: Forty patients with NSCLC with EGFR mutations who were treated with gefitinib or erlotinib and had archival tissue specimens available were enrolled in the study. KRAS mutations were analyzed by direct sequencing. Results: Three (7.5%) of the 40 patients had progressive disease, and two (67%) of these three individuals had both KRAS and EGFR mutations. Conclusions: Our Results suggest that KRAS mutation is a negative predictor of response to EGFR-TKIs in EGFR mutation-positive patients with NSCLC.

Original languageEnglish
Pages (from-to)399-400
Number of pages2
JournalJournal of Thoracic Oncology
Volume5
Issue number3
DOIs
Publication statusPublished - Mar 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine

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