T790M mutation is associated with better efficacy of treatment beyond progression with EGFR-TKI in advanced NSCLC patients

Lung Cancer. 2014 Jun;84(3):295-300. doi: 10.1016/j.lungcan.2014.03.011. Epub 2014 Mar 15.


Background and purpose: Continuous EGFR-TKI treatment beyond progression has shown promising benefit for some patients with acquired resistance to EGFR-TKIs. The aim of this study was to investigate the association of secondary T790M mutation at the time of progression with the efficacy of EGFR-TKI treatment beyond progression.

Methods: From March 2011 to March 2013, patients with advanced NSCLC who developed acquired resistance to EGFR-TKI and where a re-biopsy was performed at Tongji University Cancer Institute were included into this study. Scorpion ARMS was used to detect EGFR mutation status.

Results: A total of 54 patients were enrolled in this study with a median progression-free survival time (PFS1) of 10.9 months according to RECIST criteria. In all, 53.7% (29/54) had T790M mutation after the failure of EGFR-TKIs; PFS1 was not statistically significantly different between patients with T790M mutation and without (13.0 vs. 10.5 months, p = 0.894). In all, 41 patients received TKI treatment beyond progression, including 22 with local progression to receive additional local therapy and 19 with gradual progression to receive additional chemotherapy. The median progression-free survival time (PFS2) of patients who received EGFR-TKI beyond progression treatment was 3.5 months (95% CI, 2.689-4.311). Patients with T790M mutation had significantly longer PFS2 (6.3 vs. 2.6 months, p = 0.002) and overall survival (39.8 vs. 23.2 months, p = 0.044) than those without.

Conclusion: Patients with secondary T790M mutation at the time of progression having gradual or local progression after acquired resistance to EGFR-TKI benefit more from EGFR-TKI treatment beyond progression compared to those without T790M mutation.

Keywords: Acquired assistance; EGFR-TKI; NSCLC; Secondary T790M mutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Crown Ethers / therapeutic use
  • DNA Mutational Analysis
  • Disease Progression
  • Drug Resistance, Neoplasm / genetics*
  • ErbB Receptors / genetics*
  • Erlotinib Hydrochloride
  • Female
  • Gefitinib
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Mutation*
  • Polymerase Chain Reaction
  • Prognosis
  • Proportional Hazards Models
  • Protein Kinase Inhibitors / therapeutic use
  • Quinazolines / therapeutic use


  • Antineoplastic Agents
  • Crown Ethers
  • Protein Kinase Inhibitors
  • Quinazolines
  • icotinib
  • Erlotinib Hydrochloride
  • EGFR protein, human
  • ErbB Receptors
  • Gefitinib