title: Activity of epidermal growth factor receptor-tyrosine kinase inhibitors in patients with non-small cell lung cancer harboring rare epidermal growth factor receptor mutations.
abstract: BACKGROUND
  Mutations of the epidermal growth factor receptor (EGFR) have been proven to predict activity of the EGFR-tyrosine kinase inhibitors (EGFR-TKI), gefitinib and erlotinib. Although the "common" EGFR mutations, such as the L858R point mutation in exon 21 and the in-frame deletional mutation in exon 19, have been definitively associated with response to EGFR-TKIs, the correlation with response to treatment for many other rarer mutations is still unclear. In this study, we report the results of treating patients with advanced non-small cell lung cancer harboring rare EGFR mutations treated with EGFR-TKIs.
  
  
  METHODS
  The frequency of rare mutations has been investigated in 681 cases of non-small cell lung cancer screened between 2006 and 2010. Mutations in exons 18 and 20, uncommon mutations in exons 19 and 21, and/or the presence of different mutations in a single tumor (complex mutations) were considered rare.
  
  
  RESULTS
  EGFR mutations were detected in 99 tumors (14.5%). Eighteen cases carried rare mutations, and 10 of these patients were treated with erlotinib or gefitinib. The clinical outcome was described case by case with references to the literature. Of note, we found two EGFR mutations never identified before and one of unknown response to EGFR-TKIs.
  
  
  CONCLUSIONS
  Gefitinib and erlotinib have different antitumor activity according to the type of the EGFR mutation borne. Report of cases harboring rare mutations can support the decision-making process in this subset of patients.
authors.affiliation: Medical Oncology Unit of Respiratory Tract and Sarcomas, European Institute of Oncology, Milan, Italy. tommaso.de-pas@ieo.it
authors.forename: Tommaso
authors.initials: T
authors.lastname: De Pas
authors.forename: Francesca
authors.initials: F
authors.lastname: Toffalorio
authors.forename: Michela
authors.initials: M
authors.lastname: Manzotti
authors.forename: Caterina
authors.initials: C
authors.lastname: Fumagalli
authors.forename: Gianluca
authors.initials: G
authors.lastname: Spitaleri
authors.forename: Chiara
authors.initials: C
authors.lastname: Catania
authors.forename: Angelo
authors.initials: A
authors.lastname: Delmonte
authors.forename: Monica
authors.initials: M
authors.lastname: Giovannini
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Spaggiari
authors.forename: Filippo
authors.initials: F
authors.lastname: de Braud
authors.forename: Massimo
authors.initials: M
authors.lastname: Barberis
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011799:Quinazolines / Q000008:administration & dosage; D012189:Retrospective Studies; D012196:Review Literature as Topic; D016896:Treatment Outcome
chemical_list: D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib