title: 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.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy.
authors: Sara
authors: S
authors: Pilotto
authors: Clinical Trials Unit, National Cancer Institute, Napoli, Italy.
authors: Massimo
authors: M
authors: Di Maio
authors: Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy.
authors: Umberto
authors: U
authors: Peretti
authors: Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy.
authors: Stefania
authors: S
authors: Kinspergher
authors: Department of Pathology and Diagnostic, A.O.U.I., University of Verona, Verona, Italy.
authors: Matteo
authors: M
authors: Brunelli
authors: Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy.
authors: Francesco
authors: F
authors: Massari
authors: Biostatistics, Regina Elena National Cancer Institute, Rome, Italy.
authors: Isabella
authors: I
authors: Sperduti
authors: Biostatistics, Regina Elena National Cancer Institute, Rome, Italy.
authors: Diana
authors: D
authors: Giannarelli
authors: Division of Pulmonary Oncology, IEO, Milan, Italy.
authors: Filippo
authors: F
authors: De Marinis
authors: Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy.
authors: Giampaolo
authors: G
authors: Tortora
authors: Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy. Electronic address: emiliobria@yahoo.it.
authors: Emilio
authors: E
authors: Bria
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D066246:ErbB Receptors / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis
chemical_list: D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases
keywords: Afatinib; Erlotinib; Ethnicity; Gefitinib; Lung cancer; Meta-analysis; Trial design