title: Exon 19 deletion mutations of epidermal growth factor receptor are associated with prolonged survival in non-small cell lung cancer patients treated with gefitinib or erlotinib.
abstract: OBJECTIVE
  Somatic mutations in the epidermal growth factor receptor (EGFR) have been detected in patients with non-small cell lung cancer (NSCLC) and are associated with sensitivity to treatment with gefitinib or erlotinib. Our study explored the relationship between the two most common types of somatic EGFR mutations, exon 19 deletions and the L858R point mutation, and outcomes of patients following treatment with gefitinib or erlotinib.
  
  
  METHODS
  Tumor specimens obtained before treatment with gefitinib or erlotinib were analyzed for EGFR mutations. Patients with exon 19 deletion or L858R mutations were identified. The response rate, time to progression, and overall survival were determined for the two groups.
  
  
  RESULTS
  We identified 36 patients with NSCLC and an EGFR mutation who were treated with gefitinib or erlotinib. Patients with an exon 19 deletion had a significantly longer overall survival compared with patients with an L858R mutation (38 versus 17 months; P = 0.04). There were also trends toward higher response rate (73% versus 50%) and improved time to progression (24 versus 10 months) for the patients with an exon 19 deletion, although these were not independently significant in a multivariate analysis. A difference in response rate for patients treated with gefitinib compared with erlotinib was also noted [18 of 23 (78%) versus 3 of 9 (33%); P = 0.04]. No obvious difference in time to progression or overall survival was noted between gefitinib- and erlotinib-treated patients.
  
  
  CONCLUSIONS
  Patients with NSCLC and EGFR exon 19 deletions have a longer survival following treatment with gefitinib or erlotinib compared with those with the L858R mutation. Pooling of greater numbers of patients and completion of prospective trials are needed to further define the predictive and prognostic roles of different EGFR mutations with respect to treatment with gefitinib, erlotinib, and other EGFR inhibitors.
authors.affiliation: Lowe Center of Thoracic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Jackman
authors.forename: Beow Y
authors.initials: BY
authors.lastname: Yeap
authors.forename: Lecia V
authors.initials: LV
authors.lastname: Sequist
authors.forename: Neal
authors.initials: N
authors.lastname: Lindeman
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Holmes
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Joshi
authors.forename: Daphne W
authors.initials: DW
authors.lastname: Bell
authors.forename: Mark S
authors.initials: MS
authors.lastname: Huberman
authors.forename: Balazs
authors.initials: B
authors.lastname: Halmos
authors.forename: Michael S
authors.initials: MS
authors.lastname: Rabin
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Haber
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Lynch
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Johnson
authors.forename: Pasi A
authors.initials: PA
authors.lastname: Jänne
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D004273:DNA, Neoplasm / Q000032:analysis; D018450:Disease Progression; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D005091:Exons; D005260:Female; D005500:Follow-Up Studies; D000077156:Gefitinib; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017354:Point Mutation; D011799:Quinazolines / Q000627:therapeutic use*; D012189:Retrospective Studies; D017384:Sequence Deletion; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D004273:DNA, Neoplasm; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000077156:Gefitinib