title: Examining Treatment Outcomes with Erlotinib in Patients with Advanced Non-Small Cell Lung Cancer Whose Tumors Harbor Uncommon EGFR Mutations.
abstract: BACKGROUND
  Exon 19 deletions and the exon 21 L858R mutation of the epidermal growth factor receptor gene (EGFR) predict activity of EGFR tyrosine kinase inhibitors, including erlotinib; however, the ability of less common EGFR mutations to predict efficacy of erlotinib is unclear.
  
  
  METHODS
  The efficacy of erlotinib in individual patients with rare EGFR mutations from the MERIT, SATURN, TITAN, TRUST, ATLAS, BeTa, and FASTACT-2 trials was analyzed and compared with data from the literature.
  
  
  RESULTS
  In the patients tested for biomarkers, the frequency of rare mutations identified here ranged from 1.7% (eight of 467) in the SATURN study to 7.4% (27 of 364) in ATLAS. Some rare mutations were associated with greater clinical benefit from EGFR tyrosine kinase inhibitor therapy or improved prognosis independent of treatment, whereas others appeared to have a poorer prognosis. In particular, exon 18 G719 mutations, exon 19 K757R and E746G mutations, the exon 20 S768I mutation, and the exon 21 G836S mutation appeared to confer a good outcome with erlotinib treatment, whereas exon 18 S720I showed a particularly poor outcome. Owing to the small number of patients with each mutation, however, it is difficult to confirm whether these rare mutations do indeed confer sensitivity or resistance to erlotinib.
  
  
  CONCLUSIONS
  Erlotinib can have different efficacy depending on the specific EGFR mutation. More research is needed to create a central database such as the My Cancer Genome database of rare mutations to definitively confirm whether these mutations are activating, resistant, or neutral.
authors.affiliation: F. Hoffmann-La Roche Ltd, Basel, Switzerland. Electronic address: Barbara.klughammer@roche.com.
authors.forename: Barbara
authors.initials: B
authors.lastname: Klughammer
authors.affiliation: Schwarzwald-Baar Klinikum, Academic Teaching Hospital, University of Freiburg, Villingen-Schwenningen, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Brugger
authors.affiliation: Istituto Toscano Tumori, Ospedale Civile, Livorno, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Cappuzzo
authors.affiliation: Prof. Dr. Ion Chiricuţă Institute of Oncology, Department of Medical Oncology; Universitatea de Medicină şi Farmacie Iuliu Haţieganu, Cluj-Napoca, Romania.
authors.forename: Tudor
authors.initials: T
authors.lastname: Ciuleanu
authors.affiliation: State Key Laboratory of Southern China, Hong Kong Cancer Institute, Department of Clinical Oncology, Prince of Wales Hospital, Hong Kong, China.
authors.forename: Tony
authors.initials: T
authors.lastname: Mok
authors.affiliation: Department of Thoracic Oncology, LungenClinic Grosshansdorf, Airway Research Center North, Grosshansdorf, Germany; German Research Center for Lung Diseases.
authors.forename: Martin
authors.initials: M
authors.lastname: Reck
authors.affiliation: Department of Medical Oncology, National Cancer Centre, Singapore.
authors.forename: Eng Huat
authors.initials: EH
authors.lastname: Tan
authors.affiliation: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: Paul
authors.initials: P
authors.lastname: Delmar
authors.affiliation: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Klingelschmitt
authors.affiliation: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: Anny-Yue
authors.initials: AY
authors.lastname: Yin
authors.affiliation: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: Olivia
authors.initials: O
authors.lastname: Spleiss
authors.affiliation: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: Lin
authors.initials: L
authors.lastname: Wu
authors.affiliation: Oncology Biomarker Development, Genentech Inc., San Francisco, California.
authors.forename: David S
authors.initials: DS
authors.lastname: Shames
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D002986:Clinical Trials as Topic; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR mutations; Erlotinib; NSCLC; Rare; Uncommon