Predictors of outcome for patients with lung adenocarcinoma carrying the epidermal growth factor receptor mutation receiving 1st-line tyrosine kinase inhibitors: Sensitivity and meta-regression analysis of randomized trials

Crit Rev Oncol Hematol. 2014 May;90(2):135-45. doi: 10.1016/j.critrevonc.2013.11.005. Epub 2013 Dec 1.

Abstract

Purpose: We performed a sensitivity and meta-regression analysis, cumulating all randomized trials exploring the benefit of afatinib, erlotinib and gefitinib versus chemotherapy in advanced EGFR mutant NSCLC, to investigate the potential role of additional clinico-pathological predictors of TKIs efficacy.

Results: With regard to progression-free survival (PFS), a significant interaction according to ethnicity (Asian versus Caucasian versus mixed) and to trial design (retrospective versus prospective EGFR analysis), was found; a trend toward significance with regard to type of drug (gefitinib versus erlotinib versus afatinib) was determined. No statistically significant differences in survival were observed. With regard to response, a significant interaction according to ethnicity, trial design and type of drug, was found.

Conclusion: These data, together with a deeper characterization of the molecular background sustaining the oncogenic process, may contribute to create a clinico-pathologic predictive model, aimed to improve the magnitude of benefit expected from the use of targeted agents.

Keywords: Afatinib; Erlotinib; Ethnicity; Gefitinib; Lung cancer; Meta-analysis; Trial design.

Publication types

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

MeSH terms

  • Adenocarcinoma / drug therapy*
  • ErbB Receptors / genetics*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Mutation*
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Randomized Controlled Trials as Topic*
  • Regression Analysis

Substances

  • Protein Kinase Inhibitors
  • ErbB Receptors
  • Protein-Tyrosine Kinases