title: How sensitive are epidermal growth factor receptor-tyrosine kinase inhibitors for squamous cell carcinoma of the lung harboring EGFR gene-sensitive mutations?
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) mutations are found mostly in adenocarcinoma, and rarely in squamous cell carcinoma (SQC). Little is known about SQC harboring EGFR mutations.
  
  
  METHODS
  Between April 2006 and October 2010, we investigated the incidence of EGFR activating mutations in SQC of the lung using the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method. The efficacy of EGFR-tyrosine kinase inhibitors (TKIs) was retrospectively evaluated in patients with EGFR-mutated SQC. Further pathologic analyses were performed using immunohistochemistry.
  
  
  RESULTS
  Thirty-three of 249 patients with SQC (13.3%) had EGFR mutations, including exon 19 deletion (19 of 33 patients, 58%), L858R point mutation in exon 21 (12 of 33, 36%), and G719S point mutation in exon 18 (2 of 33, 6%). Twenty of these 33 patients received EGFR-TKI therapy, and five of these 20 responded to EGFR-TKIs with a response rate of 25.0% (95% confidence interval [CI], 8.7%-49.1%). The patients' median progression-free survival and median overall survival were 1.4 months (95% CI, 0.7-5.8 months) and 14.6 months (95% CI, 2.9-undeterminable months), respectively. Approximately one third of the EGFR-mutated SQC patients achieved progression-free survival for longer than 6 months. Some of these patients had high carcinoembryonic antigen levels or a history of never smoking, or were positive for thyroid transcription factor-1.
  
  
  CONCLUSIONS
  Although EGFR-TKIs seem to be generally less effective in EGFR-mutated SQC than in EGFR-mutated adenocarcinoma, some EGFR-mutated SQC patients can obtain clinical benefit from EGFR-TKIs. To better identify these patients, not only EGFR mutation status, but also clinical factors and pathologic findings should be taken into consideration.
authors.affiliation: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe, Japan.
authors.forename: Akito
authors.initials: A
authors.lastname: Hata
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Katakami
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Yoshioka
authors.forename: Kei
authors.initials: K
authors.lastname: Kunimasa
authors.forename: Shiro
authors.initials: S
authors.lastname: Fujita
authors.forename: Reiko
authors.initials: R
authors.lastname: Kaji
authors.forename: Kenji
authors.initials: K
authors.lastname: Notohara
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Imai
authors.forename: Ryo
authors.initials: R
authors.lastname: Tachikawa
authors.forename: Keisuke
authors.initials: K
authors.lastname: Tomii
authors.forename: Yohei
authors.initials: Y
authors.lastname: Korogi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Iwasaku
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nishiyama
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ishida
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics*; D016001:Confidence Intervals; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D005091:Exons; D005260:Female; D000077156:Gefitinib; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use; D012189:Retrospective Studies; D017384:Sequence Deletion
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000077156:Gefitinib