title: [Oncogenic drivers in daily practice improve overall survival in patients with lung adenocarcinoma].
abstract: BACKGROUND
  EGFR tyrosine kinase inhibitors and crizotinib are nowadays the optimal treatment for metastatic lung cancer with activation of EGFR mutations and ALK rearrangement. In addition, several targeted agents are in development for lung cancer with other oncodrivers. In France, since 2011, six oncodrivers are routinely tested in patients with stage IV. The aim of this study was to assess whether systematic detection of oncodrivers and matched targeted therapy improve overall survival in patients with advanced lung adenocarcinoma.
  
  
  METHODS
  This study included all consecutive patients treated in our department for advanced lung adenocarcinoma from January 2012 to December 2013. We studied the impact in survival according to the presence of the driver and the targeted therapy.
  
  
  RESULTS
  Among the 261 patients included, oncodrivers alterations were found in 43.5% of patients: EML4-ALK fusion genes (2.1%), EGFR (10.3%), KRAS (27.7%), BRAF (2.5%), HER2 (0.8%), and PI3KCA (0.8%) mutations. Twenty-nine percent of patients (n=32) with oncodrivers received matched targeted therapy. Patient treated by targeted agent appropriate to an oncogenic driver had a median survival of 21.1 months (95% CI: 14.7-27.5). The patients (n=79) who did not receive targeted therapy had a median survival of 6.6 months (95% CI: 4.3-8.9). The patients (n=150) without identified driver had a median survival of 9.7 months (95% CI: 6.7-11.7); P<0.001.
  
  
  CONCLUSIONS
  An actionable oncodriver was routinely detected in nearly half of patients with advanced lung adenocarcinoma. This systematic detection may influence treatment outcomes, notably with matched targeted therapy.
authors.affiliation: Service d'oncologie multidisciplinaire et innovations thérapeutiques, Aix-Marseille université, Assistance publique-Hôpitaux de Marseille, chemin des Bourrely, 13915 Marseille cedex 20, France. Electronic address: clotilde.fournier@ap-hm.fr.
authors.forename: C
authors.initials: C
authors.lastname: Fournier
authors.affiliation: Service d'oncologie multidisciplinaire et innovations thérapeutiques, Aix-Marseille université, Assistance publique-Hôpitaux de Marseille, chemin des Bourrely, 13915 Marseille cedex 20, France; Faculté de médecine, Aix-Marseille université, Inserm U911 CRO2, 13915 Marseille, France.
authors.forename: L
authors.initials: L
authors.lastname: Greillier
authors.affiliation: Faculté de médecine, Aix-Marseille université, Inserm U911 CRO2, 13915 Marseille, France; Laboratoire de transfert d'oncologie biologique, Aix-Marseille université, Assistance publique-Hôpitaux de Marseille, 13915 Marseille, France.
authors.forename: F
authors.initials: F
authors.lastname: Fina
authors.affiliation: Laboratoire d'anatomie pathologique, Aix-Marseille université, Assistance publique-Hôpitaux de Marseille, 13915 Marseille, France.
authors.forename: V
authors.initials: V
authors.lastname: Secq
authors.affiliation: Faculté de médecine, Aix-Marseille université, Inserm U911 CRO2, 13915 Marseille, France; Laboratoire de transfert d'oncologie biologique, Aix-Marseille université, Assistance publique-Hôpitaux de Marseille, 13915 Marseille, France.
authors.forename: I
authors.initials: I
authors.lastname: Nanni-Metellus
authors.affiliation: Unité de recherche en santé publique, maladies chroniques et qualité de vie, EA 3279, Aix-Marseille université, 13915 Marseille, France.
authors.forename: A
authors.initials: A
authors.lastname: Loundou
authors.affiliation: Laboratoire d'anatomie pathologique, Aix-Marseille université, Assistance publique-Hôpitaux de Marseille, 13915 Marseille, France.
authors.forename: S
authors.initials: S
authors.lastname: Garcia
authors.affiliation: Faculté de médecine, Aix-Marseille université, Inserm U911 CRO2, 13915 Marseille, France; Laboratoire de transfert d'oncologie biologique, Aix-Marseille université, Assistance publique-Hôpitaux de Marseille, 13915 Marseille, France.
authors.forename: L
authors.initials: L
authors.lastname: Ouafik
authors.affiliation: Service d'oncologie multidisciplinaire et innovations thérapeutiques, Aix-Marseille université, Assistance publique-Hôpitaux de Marseille, chemin des Bourrely, 13915 Marseille cedex 20, France; Faculté de médecine, Aix-Marseille université, Inserm U911 CRO2, 13915 Marseille, France.
authors.forename: P
authors.initials: P
authors.lastname: Tomasini
authors.affiliation: Service d'oncologie multidisciplinaire et innovations thérapeutiques, Aix-Marseille université, Assistance publique-Hôpitaux de Marseille, chemin des Bourrely, 13915 Marseille cedex 20, France; Faculté de médecine, Aix-Marseille université, Inserm U911 CRO2, 13915 Marseille, France.
authors.forename: F
authors.initials: F
authors.lastname: Barlesi
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D000077547:Crizotinib; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D008297:Male; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D009857:Oncogenes; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000077547:Crizotinib; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D011720:Pyrazoles; D011725:Pyridines; D018719:Erb-b2 Receptor Tyrosine Kinases; D014157:Transcription Factors; C522504:EML4-ALK fusion protein, human; C117307:KRAS protein, human; C503859:PI3KCA protein, human; C508053:ERBB2 protein, human; C482119:BRAF protein, human
keywords: Biomarqueur; Cancer bronchique; Clinical trial; Essai clinique; Lung cancer; Oncogenic driver; Targeted therapy; Thérapie ciblée