title: Protein kinase inhibitors to treat non-small-cell lung cancer.
abstract: BACKGROUND
  Activating mutations of the EGFR and rearrangement of anaplastic lymphoma kinase (ALK) best illustrate the therapeutic relevance of molecular characterization in NSCLC patients.
  
  
  METHODS
  For this review article, all published data on the most relevant Phase III trials with tyrosine kinase inhibitors (TKIs) for the treatment of NSCLC were collected and analyzed.
  
  
  CONCLUSIONS
  Eight Phase III trials clearly established EGFR TKIs as the best therapeutic option for front-line therapy in EGFR-mutated patients. In pretreated NSCLC, EGFR TKIs are considered more effective than standard monotherapy with cytotoxics in presence of classical EGFR mutations, whereas in the EGFR wild-type population, a similar efficacy to docetaxel or pemetrexed in term of survival has been demonstrated. In ALK-translocated NSCLC, a Phase III trial demonstrated the superiority of a multi-target TKI, including ALK, in terms of progression-free survival, response rate and toxicity profile when compared to standard second-line chemotherapy. New agents targeting EGFR or ALK are under evaluation particularly in individuals with acquired resistance to EGFR TKIs or crizotinib.
authors.affiliation: Istituto Toscano Tumori, Ospedale Civile, Oncologia Medica , Viale Alfieri 36, 57100-Livorno , Italy +39 0586223189 ; +39 0586223457 ; f.cappuzzo@gmail.com.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Minuti
authors.forename: Armida
authors.initials: A
authors.lastname: D'Incecco
authors.forename: Lorenza
authors.initials: L
authors.lastname: Landi
authors.forename: Federico
authors.initials: F
authors.lastname: Cappuzzo
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology; D000077547:Crizotinib; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases
keywords: NSCLC; afatinib; crizotinib; erlotinib; gefitinib