Clinical Factors Predicting Detection of T790M Mutation in Rebiopsy for EGFR-Mutant Non-small-cell Lung Cancer

Takahisa Kawamura, Hirotsugu Kenmotsu, Shota Omori, Kazuhisa Nakashima, Kazushige Wakuda, Akira Ono, Tateaki Naito, Haruyasu Murakami, Katsuhiro Omae, Keita Mori, Yusuke Tanigawara, Takashi Nakajima, Yasuhisa Ohde, Masahiro Endo, Toshiaki Takahashi

研究成果: Article

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Background: T790M, a secondary epidermal growth factor receptor (EGFR) mutation, accounts for approximately 50% of acquired resistance to EGFR-tyrosine kinase inhibitors (TKIs). To facilitate the use of third-generation EGFR-TKIs to potentially overcome T790M-mediated resistance, we evaluated the clinical factors influencing the incidence of T790M mutation. Patients and Methods: We retrospectively screened patients with non-small-cell lung cancer harboring EGFR mutations with progressive disease who were rebiopsied between January 2013 and December 2016. Factors influencing T790M status were evaluated by univariate and multivariate analysis. Results: Among 131 rebiopsied patients for whom EGFR mutation status was available, 58 (44%) had T790M mutations. Patient characteristics at rebiopsy were not significantly different between T790M-positive and -negative groups, except for surgical history (postsurgery recurrence). Total duration of EGFR-TKI treatment before rebiopsy, TKI-free interval, EGFR-TKI treatment history immediately before rebiopsy, continuation of initial EGFR-TKI beyond progressive disease, progression-free survival after initial TKI treatment, and rebiopsy site (other than fluid samples) significantly influenced T790M status. The incidence of T790M mutation was shown by multivariate analysis to be significantly higher in patients with postsurgery recurrence and total duration of EGFR-TKI treatment ≥ 1 year before rebiopsy (odds ratio, 4.2; 95% confidence interval, 1.3-15.7 and odds ratio, 4.4; 95% confidence interval, 1.1-19.8, respectively). Conclusion: Postsurgery recurrence and longer total duration of EGFR-TKI treatment before rebiopsy may represent useful predictive markers for T790M detection. In patients with these clinical factors, rebiopsies are more recommended to detect T790M mutation.

元の言語English
ジャーナルClinical Lung Cancer
DOI
出版物ステータスAccepted/In press - 2017

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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    Kawamura, T., Kenmotsu, H., Omori, S., Nakashima, K., Wakuda, K., Ono, A., Naito, T., Murakami, H., Omae, K., Mori, K., Tanigawara, Y., Nakajima, T., Ohde, Y., Endo, M., & Takahashi, T. (受理済み/印刷中). Clinical Factors Predicting Detection of T790M Mutation in Rebiopsy for EGFR-Mutant Non-small-cell Lung Cancer. Clinical Lung Cancer. https://doi.org/10.1016/j.cllc.2017.07.002