Takahisa Kawamura1, Hirotsugu Kenmotsu2, Shota Omori1, Kazuhisa Nakashima1, Kazushige Wakuda1, Akira Ono1, Tateaki Naito1, Haruyasu Murakami1, Katsuhiro Omae3, Keita Mori3, Yusuke Tanigawara4, Takashi Nakajima5, Yasuhisa Ohde6, Masahiro Endo7, Toshiaki Takahashi1. 1. Division of Thoracic Oncology, Shizuoka Cancer Center, Suntou-gun, Shizuoka, Japan. 2. Division of Thoracic Oncology, Shizuoka Cancer Center, Suntou-gun, Shizuoka, Japan. Electronic address: h.kenmotsu@scchr.jp. 3. Clinical Research Center, Shizuoka Cancer Center, Suntou-gun, Shizuoka, Japan. 4. Department of Clinical Pharmacokinetics and Pharmacodynamics, Keio University School Medicine, Tokyo, Japan. 5. Division of Pathology, Shizuoka Cancer Center, Suntou-gun, Shizuoka, Japan. 6. Division of Thoracic Surgery, Shizuoka Cancer Center, Suntou-gun, Shizuoka, Japan. 7. Division of Diagnostic Radiology, Shizuoka Cancer Center, Suntou-gun, Shizuoka, Japan.
Abstract
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.
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.