Therapeutic Efficacy Comparison of 5 Major EGFR-TKIs in Advanced EGFR-positive Non-Small-cell Lung Cancer: A Network Meta-analysis Based on Head-to-Head Trials

Clin Lung Cancer. 2017 Sep;18(5):e333-e340. doi: 10.1016/j.cllc.2016.09.006. Epub 2016 Oct 27.

Abstract

Background: Five major first- and second-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), including erlotinib, gefitinib, icotinib, afatinib, and dacomitinib, are currently optional for patients with advanced non-small-cell lung cancer (NSCLC) who harbor EGFR mutations. However, there was no head-to-head-based network meta-analysis among all the TKIs in EGFR-mutated populations.

Methods: Eligible literature was searched from an electronic database. Data of objective response rate, disease control rate, progression-free survival, and overall survival were extracted from enrolled studies. Multiple treatment comparisons based on Bayesian network integrated the efficacy of all included treatments.

Results: Six phase III randomized trials involving 1055 EGFR-mutated patients with advanced NSCLC were enrolled. Multiple treatment comparisons showed that 5 different EGFR-TKIs shared equivalent therapeutic efficacy in terms of all outcome measures. Rank probabilities indicated that dacomitinib and afatinib had potentially better efficacy compared with erlotinib, gefitinib, and icotinib in the EGFR-mutated patients. When compared with other agents, potential survival benefits (progression-free and overall survival) were observed in dacomitinib, whereas afatinib showed a better rank probability in overall response rate and disease control rate.

Conclusion: Our study indicated a preferable therapeutic efficacy in the second-generation TKIs (dacomitinib and afatinib) when compared with the first-generation TKIs (erlotinib, gefitinib, and icotinib).

Keywords: Afatinib; Dacomitinib; Erlotinib; Gefitinib; Icotinib.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Review

MeSH terms

  • Afatinib
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Clinical Trials, Phase III as Topic
  • Crown Ethers / therapeutic use
  • Disease-Free Survival
  • ErbB Receptors / antagonists & inhibitors*
  • Erlotinib Hydrochloride / therapeutic use
  • Gefitinib
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Network Meta-Analysis
  • Protein Kinase Inhibitors / therapeutic use*
  • Quinazolines / therapeutic use
  • Quinazolinones / therapeutic use
  • Randomized Controlled Trials as Topic
  • Survival Rate

Substances

  • Antineoplastic Agents
  • Crown Ethers
  • Protein Kinase Inhibitors
  • Quinazolines
  • Quinazolinones
  • Afatinib
  • dacomitinib
  • icotinib
  • Erlotinib Hydrochloride
  • ErbB Receptors
  • Gefitinib