Biological and clinical features in predicting efficacy of epidermal growth factor receptor tyrosine kinase inhibitors: A systematic review and meta-analysis

Marina Chiara Garassino, Karen Borgonovo, Antonio Rossi, Andrea Mancuso, Olga Martelli, Angelo Tinazzi, Serena Di Cosimo, Nicla La Verde, Paola Sburlati, Celso Bianchi, Gabriella Farina, Valter Torri

Research output: Contribution to journalArticle

Abstract

Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), developed for patients with advanced non-small cell lung cancer (NSCLC), give modest results similar to those with chemotherapy. There is evidence of a greater survival benefit from TKIs in patients with certain molecular and clinical features, but results are conflicting. To assess the role of these factors in predicting TKI efficacy, a pooled analysis was performed on data from randomized trials in NSCLC. Materials and Methods: An electronic search of all randomized trials comparing the efficacy or activity of TKIs and a pooled analysis were performed. The hazard ratio (HR) with 95% confidence interval (CI) was calculated for each level of the factors and an interaction test was used to detect differences in treatment effect related to the different levels. Results: Of ten randomized trials identified, five were considered for analysis. Smoking was shown to be the only clinical factor to have a predictive effect (non smokers: overall survival (OS) HR 0.53, 95% CI 0.42-0.67; smokers: HR 0.91, 95% CI 0.81-1.02; p-value for interaction +: HR 1.9795% CI 1.16-3.33; K-ras-: HR 0.79, 95% CI 0.59-1.05; p-value for interaction 0.003). Conclusion: At the present time, none of the biological features which have been evaluated in patients who have undergone therapy using TKIs is proven to be of predictive value; only K-ras mutations and smoking habits can be considered as a possible criteria for selection. Results of prospective randomized trials on biological markers are awaited.

Original languageEnglish
Pages (from-to)2691-2701
Number of pages11
JournalAnticancer Research
Volume29
Issue number7
Publication statusPublished - Jul 2009

Keywords

  • EGFR mutations
  • Erlotinib
  • Gefitinib
  • K-ras mutations
  • Lung cancer
  • Predictive factors
  • Smoking habits

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Garassino, M. C., Borgonovo, K., Rossi, A., Mancuso, A., Martelli, O., Tinazzi, A., Di Cosimo, S., La Verde, N., Sburlati, P., Bianchi, C., Farina, G., & Torri, V. (2009). Biological and clinical features in predicting efficacy of epidermal growth factor receptor tyrosine kinase inhibitors: A systematic review and meta-analysis. Anticancer Research, 29(7), 2691-2701.