Clinical predictors of response to EGFR tyrosine kinase inhibitors in patients with EGFR-mutant non-small cell lung cancer

Oncology. 2014;86(2):86-93. doi: 10.1159/000357129. Epub 2014 Jan 18.

Abstract

Background: The presence of EGFR (epidermal growth factor receptor) mutations is a robust predictor of EGFR tyrosine kinase inhibitor (TKI) responsiveness. Predictors of EGFR-TKI responsiveness in EGFR-mutant non-small cell lung cancer (NSCLC) patients, however, have not been well investigated. The purpose of this study is to examine predictors of EGFR-TKI responsiveness in EGFR-mutant NSCLC patients.

Patients and methods: Seventy EGFR-mutant NSCLC patients who received EGFR-TKIs in our institution between April 2007 and March 2013 were analyzed retrospectively.

Results: The objective response rate was 50.0% (95% confidence interval, CI, 38.6-61.4%) and the disease control rate was 91.4% (95% CI, 82.5-96.0%). The median progression-free survival (PFS) and overall survival were 9.0 (95% CI, 3.92-14.08) and 20.8 months (95% CI, 14.56-27.04), respectively. In multivariate analysis, adenocarcinoma (hazard ratio, HR, 12.25; 95% CI, 37.7-41.10; p < 0.001) and major mutations (deletions in exon 19 and L858R point mutation in exon 21; HR, 2.46; 95% CI, 1.14-5.28; p = 0.022) were significant predictors of longer PFS.

Conclusion: Major mutations and adenocarcinoma histology were independent predictors of better treatment outcome in EGFR-mutant NSCLC patients who received EGFR-TKIs. Further well-controlled prospective studies are warranted to confirm our findings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / mortality
  • DNA Mutational Analysis
  • Disease-Free Survival
  • Drug Resistance, Neoplasm
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Erlotinib Hydrochloride
  • Female
  • Gefitinib
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mutation, Missense
  • Proportional Hazards Models
  • Quinazolines / pharmacology
  • Quinazolines / therapeutic use*
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Quinazolines
  • Erlotinib Hydrochloride
  • EGFR protein, human
  • ErbB Receptors
  • Gefitinib