Efficacy of EGFR tyrosine kinase inhibitors in non-small-cell lung cancer patients with/without EGFR-mutation: evidence based on recent phase III randomized trials

Med Sci Monit. 2014 Dec 15:20:2666-76. doi: 10.12659/MSM.892476.

Abstract

Background: EGFR mutation might be a predictive factor for applying EGFR-tyrosine kinase inhibitors (EGFR-TKIs, including gefitinib, erlotinib and afatinib) in non-small-cell lung cancer (NSCLS) patients. Thus, it is necessary to pool previous trials to compare the effect of EGFR-TKIs versus cytotoxic chemotherapy in EGFR mutation positive (mut+) and negative (mut-) patients.

Material and methods: This study identified 8 first-line and 9 second-line phase III trials in databases. Hazard ratio (HR) was pooled to assess the risk of progression-free survival (PFS), and overall survival (OS), while odds ratio (OR) was pooled to assess objective response, disease control, and toxicity of EGFR-TKIs verses chemotherapy.

Results: In EGFR mut+ patients, EGFR-TKIs were associated with significantly lower risk of disease progression in the first-line setting, but this trend was only observed in the gefitinib group, not in the erlotinib group in the second-line setting. In EGFR mut- patients, gefitinib and erlotinib had significantly higher risk of disease progression in first-line and second-line setting, respectively. Compared with chemotherapy, the effects of EGFR-TKIs on OS in both first-line and second-line settings were not evident. Regarding toxicity, EGFR-TKIs had significantly higher risk of rash and lower hematological toxicity compared with chemotherapy.

Conclusions: All of the 3 EGFR-TKIs and gefitinib alone regimens had better effects in prolonging PFS in EGFR mut+ patients in first-line and second-line setting, respectively, but chemotherapy seemed more effective in EGFR mut- patients than EGFR-TKIs. Therefore, accurate identification of EGFR mutation status is useful to decide on an appropriate regimen for treatment of NSCLC patients.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Clinical Trials, Phase III as Topic*
  • Disease-Free Survival
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / genetics*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Mutation / genetics*
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Randomized Controlled Trials as Topic*
  • Treatment Outcome

Substances

  • Protein Kinase Inhibitors
  • ErbB Receptors