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

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish
JournalClinical Lung Cancer
DOIs
Publication statusAccepted/In press - 2017

Fingerprint

Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Protein-Tyrosine Kinases
Mutation
Recurrence
Disease-Free Survival
Multivariate Analysis
History
Odds Ratio
Confidence Intervals
Therapeutics
Incidence
Disease Progression

Keywords

  • Acquired resistance
  • Disease progression
  • EGFR-TKI
  • Epidermal growth factor receptor
  • Predictive marker

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Kawamura, T., Kenmotsu, H., Omori, S., Nakashima, K., Wakuda, K., Ono, A., ... Takahashi, T. (Accepted/In press). 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

Clinical Factors Predicting Detection of T790M Mutation in Rebiopsy for EGFR-Mutant Non-small-cell Lung Cancer. / Kawamura, Takahisa; Kenmotsu, Hirotsugu; Omori, Shota; Nakashima, Kazuhisa; Wakuda, Kazushige; Ono, Akira; Naito, Tateaki; Murakami, Haruyasu; Omae, Katsuhiro; Mori, Keita; Tanigawara, Yusuke; Nakajima, Takashi; Ohde, Yasuhisa; Endo, Masahiro; Takahashi, Toshiaki.

In: Clinical Lung Cancer, 2017.

Research output: Contribution to journalArticle

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 2017, '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
Kawamura, Takahisa ; Kenmotsu, Hirotsugu ; Omori, Shota ; Nakashima, Kazuhisa ; Wakuda, Kazushige ; Ono, Akira ; Naito, Tateaki ; Murakami, Haruyasu ; Omae, Katsuhiro ; Mori, Keita ; Tanigawara, Yusuke ; Nakajima, Takashi ; Ohde, Yasuhisa ; Endo, Masahiro ; Takahashi, Toshiaki. / Clinical Factors Predicting Detection of T790M Mutation in Rebiopsy for EGFR-Mutant Non-small-cell Lung Cancer. In: Clinical Lung Cancer. 2017.
@article{2557a77b65f84804a49893eebe849a80,
title = "Clinical Factors Predicting Detection of T790M Mutation in Rebiopsy for EGFR-Mutant Non-small-cell Lung Cancer",
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.",
keywords = "Acquired resistance, Disease progression, EGFR-TKI, Epidermal growth factor receptor, Predictive marker",
author = "Takahisa Kawamura and Hirotsugu Kenmotsu and Shota Omori and Kazuhisa Nakashima and Kazushige Wakuda and Akira Ono and Tateaki Naito and Haruyasu Murakami and Katsuhiro Omae and Keita Mori and Yusuke Tanigawara and Takashi Nakajima and Yasuhisa Ohde and Masahiro Endo and Toshiaki Takahashi",
year = "2017",
doi = "10.1016/j.cllc.2017.07.002",
language = "English",
journal = "Clinical Lung Cancer",
issn = "1525-7304",
publisher = "Elsevier",

}

TY - JOUR

T1 - Clinical Factors Predicting Detection of T790M Mutation in Rebiopsy for EGFR-Mutant Non-small-cell Lung Cancer

AU - Kawamura, Takahisa

AU - Kenmotsu, Hirotsugu

AU - Omori, Shota

AU - Nakashima, Kazuhisa

AU - Wakuda, Kazushige

AU - Ono, Akira

AU - Naito, Tateaki

AU - Murakami, Haruyasu

AU - Omae, Katsuhiro

AU - Mori, Keita

AU - Tanigawara, Yusuke

AU - Nakajima, Takashi

AU - Ohde, Yasuhisa

AU - Endo, Masahiro

AU - Takahashi, Toshiaki

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Acquired resistance

KW - Disease progression

KW - EGFR-TKI

KW - Epidermal growth factor receptor

KW - Predictive marker

UR - http://www.scopus.com/inward/record.url?scp=85028588097&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85028588097&partnerID=8YFLogxK

U2 - 10.1016/j.cllc.2017.07.002

DO - 10.1016/j.cllc.2017.07.002

M3 - Article

C2 - 28866043

AN - SCOPUS:85028588097

JO - Clinical Lung Cancer

JF - Clinical Lung Cancer

SN - 1525-7304

ER -