Clinical modes of EGFR tyrosine kinase inhibitor failure and subsequent management in advanced non-small cell lung cancer

Lung Cancer. 2013 Jan;79(1):33-9. doi: 10.1016/j.lungcan.2012.09.016. Epub 2012 Oct 15.


Background: There is no published overview of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) failure modes in advanced non-small-cell lung cancer (NSCLC). This study aimed to classify the diversity of EGFR-TKI failure, and to investigate the usefulness of clinical modes in subsequent management and prognosis.

Methods: One-hundred and twenty consecutive clinical trial patients with EGFR-TKI failure were enrolled as the training set to establish a clinical model based on clinical factors. Another 107 routine patients were enrolled as the validating set according to a Bayes discriminant analysis. EGFR mutations and c-MET amplification were analyzed. Kaplan-Meier survival analysis was used to test the differences among three clinical modes and subsequent management.

Results: The duration of disease control, evolution of tumor burden, and clinical symptom were verified as feasible grouping variables. A correct grouping rate achieved 87.9%. The cohort was classified into three groups, as follows: 130 patients with dramatic progression, 42 with gradual progression, and 55 with local progression. Progression-free survivals (PFSs) for the dramatic progression, gradual progression, and local progression groups were 9.3, 12.9, and 9.2 months, respectively (P = 0.007). Overall survivals for the groups (OSs) were 17.1, 39.4, and 23.1 months, respectively (P < 0.001). TKI continuation was superior to switching chemotherapy in a subsequent setting for gradual progression (39.4 months vs. 17.8 months; P = 0.02). The difference of EGFR or c-MET among the three groups was not significant.

Conclusions: Clinical modes of EGFR-TKI failure could favor strategies for subsequent treatment and predicting a survival benefit in advanced NSCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / mortality
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / genetics
  • Erlotinib Hydrochloride
  • Female
  • Follow-Up Studies
  • Gefitinib
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Mutation / genetics
  • Neoplasm Staging
  • Proto-Oncogene Proteins c-met / genetics
  • Quinazolines / administration & dosage*
  • Quinazolines / adverse effects
  • Retrospective Studies
  • Survival Analysis
  • Treatment Failure
  • Tumor Burden / drug effects


  • Quinazolines
  • Erlotinib Hydrochloride
  • EGFR protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins c-met
  • Gefitinib