title: Biological and clinical features in predicting efficacy of epidermal growth factor receptor tyrosine kinase inhibitors: a systematic review and meta-analysis.
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.
  
  
  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 <0.001). A negative predictive value was suggested for K-ras mutations (K-ras(+): HR 1.97 95% CI 1.16-3.33; K-ras(-): HR 0.79, 95% CI 0.59-1.05; p-value for interaction 0.003).
  
  
  CONCLUSIONS
  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.
authors: Oncology Department, Fatebenefratelli and Ophthalmic Hospital, 20121 Milan, Italy. marina.garassino@fbf.milano.it
authors: Marina Chiara
authors: MC
authors: Garassino
authors: Karen
authors: K
authors: Borgonovo
authors: Antonio
authors: A
authors: Rossi
authors: Andrea
authors: A
authors: Mancuso
authors: Olga
authors: O
authors: Martelli
authors: Angelo
authors: A
authors: Tinazzi
authors: Serena
authors: S
authors: Di Cosimo
authors: Nicla
authors: N
authors: La Verde
authors: Paola
authors: P
authors: Sburlati
authors: Celso
authors: C
authors: Bianchi
authors: Gabriella
authors: G
authors: Farina
authors: Valter
authors: V
authors: Torri
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors