Mutation abundance affects the efficacy of EGFR tyrosine kinase inhibitor readministration in non-small-cell lung cancer with acquired resistance

Med Oncol. 2014 Jan;31(1):810. doi: 10.1007/s12032-013-0810-6. Epub 2013 Dec 14.


There is no consensus in the salvage treatment for non-small-cell lung cancer (NSCLC) with acquired resistance to primary epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). Fifty-one consecutive EGFR-mutated NSCLC patients with TKI retreatment after acquired resistance were enrolled in this study. The quantitation of mutation abundance was performed by real-time fluorescent quantitative PCR. The correlation between mutation abundance and outcomes of readministrated TKI was analyzed by survival analysis. Patients with high (H) mutation abundance (24/51) had a significantly (log-rank, P < 0.05) longer (5.27-2.53 months) median progression-free survival (PFS), compared with the low (L) abundance group (27/51), whereas the median overall survival showed no difference (21.00-18.20 months, log-rank P = .403) between the two groups. Objective response and disease control rates in group H and group L regarding the second round TKI treatment were 8.3, 70.8 and 0, 48.1 %, respectively. Groupings with different mutation abundances were significantly associated with PFS under multivariate Cox proportional hazards regression model [hazard ratio (HR) for group H vs. L, 0.527; P = .036]. Mutation abundance affects the efficacy of EGFR-TKIs readministration in NSCLC with acquired resistance. The quantitative mutation abundance of EGFR may be a potential predictor for selecting optimal patients to readministrate EGFR-TKIs after acquired resistance to primary TKI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • DNA Mutational Analysis
  • Disease-Free Survival
  • Drug Resistance, Neoplasm*
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Erlotinib Hydrochloride
  • Female
  • Gefitinib
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Metastasis
  • Proportional Hazards Models
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Quinazolines / therapeutic use
  • Regression Analysis
  • Retrospective Studies
  • Treatment Outcome


  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Quinazolines
  • Erlotinib Hydrochloride
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Gefitinib