title: Targeted Therapy for Patients with BRAF-Mutant Lung Cancer: Results from the European EURAF Cohort.
abstract: BACKGROUND
  Approximately 2% of lung adenocarcinomas have BRAF (v-Raf murine sarcoma viral oncogene homolog B) mutations, including V600E and other types. Vemurafenib, dabrafenib, and sorafenib as BRAF inhibitors are currently tested in clinical trials, but access for patients is limited. The aim of this study was to document the clinical course of patients treated outside of clinical trials.
  
  
  METHODS
  We conducted a retrospective multicenter cohort study in Europe of patients with advanced BRAF-mutant lung cancer treated with known BRAF inhibitors. Data were anonymized and centrally assessed for age, gender, smoking, histology, stage, local molecular diagnostic results, systemic therapies, and survival. Best response was assessed locally by RECIST1.1.
  
  
  RESULTS
  We documented 35 patients treated in 17 centers with vemurafenib, dabrafenib, or sorafenib. Median age was 63 years (range 42-85); gender was balanced; 14 (40%) were never smokers; all (100%) had adenocarcinoma; 29 (83%) had V600E; 6 (17%) had other mutations; one of them had a concomitant KRAS mutation. Thirty (86%) patients had chemotherapy in the first line. Overall survival with first-line therapy was 25.3 months for V600E and 11.8 months for non-V600E. Thirty-one patients received one BRAF inhibitor, and four received a second inhibitor. Overall response rate with BRAF therapy was 53%, and disease control rate was 85%. Median progression-free survival with BRAF therapy was 5.0 months, and overall survival was 10.8 months.
  
  
  CONCLUSIONS
  These results confirm the activity of targeted therapy in patients with BRAF-mutant lung adenocarcinoma. Further trials are warranted to study combination therapies and drug resistance mechanisms.
authors.affiliation: *Tumorzentrum, Luzerner Kantonsspital, Luzern, Switzerland; †Hôpital Larrey, Centre Hospital-Universitaire, Université Paul Sabatier, Toulouse, France; ‡Institut Claudius Regaud IUCT-O, Toulouse, France; §Institut Gustave Roussy, Villejuif, France; ¶VU University Medical Center, Amsterdam, The Netherlands; ‖Center of Integrated Oncology Cologne, University Hospital Cologne, Cologne, Germany; #Centre Pluridisciplinaire d'Oncologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; **Onkologie/Hämatologie, Kantonsspital St. Gallen, St. Gallen, Switzerland; ††Medizinische Klinik, St. Claraspital, Basel, Switzerland; ‡‡Service de pneumologie et oncologie thoracique, Hopital Universitaire, Caen, France; §§University Hospital Essen, Essen, Germany; ¶¶University Hospital Zurich, Zurich, Switzerland; ‖‖Clinique Teissier, Valenciennes, France; ##Centre Hospitalier Intercommunal de Creteil, Créteil, France; ***University Hospital Innsbruck, Innsbruck, Austria; †††University Hospital Basel, Basel, Switzerland; ‡‡‡Heidelberg University Medical Center, Mannheim, Germany; §§§Hopital du Haut Lévèque, Pessac, France; ¶¶¶Oncology Institute of Southern Switzerland, Bellinzona, Switzerland; and ‖‖‖Centre Hospitalier Universitaire, Université de Caen-Basse Normandie, Caen, France.
authors.forename: Oliver
authors.initials: O
authors.lastname: Gautschi
authors.forename: Julie
authors.initials: J
authors.lastname: Milia
authors.forename: Bastien
authors.initials: B
authors.lastname: Cabarrou
authors.forename: Marie-Virginia
authors.initials: MV
authors.lastname: Bluthgen
authors.forename: Benjamin
authors.initials: B
authors.lastname: Besse
authors.forename: Egbert F
authors.initials: EF
authors.lastname: Smit
authors.forename: Juergen
authors.initials: J
authors.lastname: Wolf
authors.forename: Solange
authors.initials: S
authors.lastname: Peters
authors.forename: Martin
authors.initials: M
authors.lastname: Früh
authors.forename: Dieter
authors.initials: D
authors.lastname: Koeberle
authors.forename: Youssouf
authors.initials: Y
authors.lastname: Oulkhouir
authors.forename: Martin
authors.initials: M
authors.lastname: Schuler
authors.forename: Alessandra
authors.initials: A
authors.lastname: Curioni-Fontecedro
authors.forename: Benjamin
authors.initials: B
authors.lastname: Huret
authors.forename: Mallorie
authors.initials: M
authors.lastname: Kerjouan
authors.forename: Sebastian
authors.initials: S
authors.lastname: Michels
authors.forename: Georg
authors.initials: G
authors.lastname: Pall
authors.forename: Sacha
authors.initials: S
authors.lastname: Rothschild
authors.forename: Gerald
authors.initials: G
authors.lastname: Schmid-Bindert
authors.forename: Matthias
authors.initials: M
authors.lastname: Scheffler
authors.forename: Rémi
authors.initials: R
authors.lastname: Veillon
authors.forename: Luciano
authors.initials: L
authors.lastname: Wannesson
authors.forename: Joachim
authors.initials: J
authors.lastname: Diebold
authors.forename: Gérard
authors.initials: G
authors.lastname: Zalcman
authors.forename: Thomas
authors.initials: T
authors.lastname: Filleron
authors.forename: Julien
authors.initials: J
authors.lastname: Mazières
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D047428:Protein Kinase Inhibitors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf