title: Bronchioloalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced non-small-cell lung cancer.
abstract: OBJECTIVE
  Gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, induces radiographic regressions and symptomatic improvement in patients with non-small-cell lung cancer (NSCLC). Phase II trials suggested female sex and adenocarcinoma were associated with response. We undertook this analysis to identify additional clinical and pathologic features associated with sensitivity to gefitinib.
  
  
  METHODS
  We reviewed medical records, pathologic material, and imaging studies of all 139 NSCLC patients treated on one of three consecutive studies of gefitinib monotherapy performed at our institution. We identified patients experiencing a major objective response and compared their clinical and pathologic features with the others. Univariate and multivariable analyses were performed on potential predictive features associated with sensitivity to gefitinib.
  
  
  RESULTS
  Of 139 patients, 21 (15%; 95% CI, 9% to 21%), experienced a partial radiographic response. Variables identified as significant in univariate analysis included adenocarcinoma versus other NSCLC (19% v 0%; P=.004), adenocarcinoma with bronchioloalveolar features versus other adenocarcinomas (38% v 14%; P<.001), never smoker status versus former/current (36% v 8%; P<.001), and Karnofsky performance status > or =80% versus < or =70% (22% v 8%; P=.03). Multivariable analysis revealed the presence of adenocarcinoma with any bronchioloalveolar features (P=.004) and being a never smoker (P=.006) were independent predictors of response.
  
  
  CONCLUSIONS
  Our data suggest that individuals in whom gefitinib is efficacious are more likely to have adenocarcinomas of the bronchioloalveolar subtype and to be never smokers. These observations may provide clues to mechanisms determining sensitivity to this agent and suggest that NSCLC has a different biology in patients who never smoked and those with bronchioloalveolar carcinoma.
authors.affiliation: Thoracic Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA. millerv@mskcc.org
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Miller
authors.forename: Mark G
authors.initials: MG
authors.lastname: Kris
authors.forename: Neelam
authors.initials: N
authors.lastname: Shah
authors.forename: Jyoti
authors.initials: J
authors.lastname: Patel
authors.forename: Christopher
authors.initials: C
authors.lastname: Azzoli
authors.forename: Jorge
authors.initials: J
authors.lastname: Gomez
authors.forename: Lee M
authors.initials: LM
authors.lastname: Krug
authors.forename: William
authors.initials: W
authors.lastname: Pao
authors.forename: Naiyer
authors.initials: N
authors.lastname: Rizvi
authors.forename: Barbara
authors.initials: B
authors.lastname: Pizzo
authors.forename: Leslie
authors.initials: L
authors.lastname: Tyson
authors.forename: Ennapadam
authors.initials: E
authors.lastname: Venkatraman
authors.forename: Leah
authors.initials: L
authors.lastname: Ben-Porat
authors.forename: Natalie
authors.initials: N
authors.lastname: Memoli
authors.forename: Maureen
authors.initials: M
authors.lastname: Zakowski
authors.forename: Valerie
authors.initials: V
authors.lastname: Rusch
authors.forename: Robert T
authors.initials: RT
authors.lastname: Heelan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002283:Carcinoma, Bronchogenic / Q000188:drug therapy* / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors; D005260:Female; D000077156:Gefitinib; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000494:pharmacology*; D012189:Retrospective Studies; D012907:Smoking
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D004815:Epidermal Growth Factor; D011505:Protein-Tyrosine Kinases; D000077156:Gefitinib