title: Impact on disease-free survival of adjuvant erlotinib or gefitinib in patients with resected lung adenocarcinomas that harbor EGFR mutations.
abstract: BACKGROUND
  Patients with stage IV lung adenocarcinoma and epidermal growth factor receptor (EGFR) mutation derive clinical benefit from treatment with EGFR tyrosine kinase inhibitors (TKIs). Whether treatment with TKI improves outcomes in patients with resected lung adenocarcinoma and EGFR mutation is unknown.
  
  
  METHODS
  Data were analyzed from a surgical database of patients with resected lung adenocarcinoma harboring EGFR exon 19 or 21 mutations. In a multivariate analysis, we evaluated the impact of treatment with adjuvant TKI.
  
  
  RESULTS
  The cohort consists of 167 patients with completely resected stages I to III lung adenocarcinoma. Ninety-three patients (56%) had exon 19 del, 74 patients (44%) had exon 21 mutations, and 56 patients (33%) received perioperative TKI. In a multivariate analysis controlling for sex, stage, type of surgery, and adjuvant platinum chemotherapy, the 2-year disease-free survival (DFS) was 89% for patients treated with adjuvant TKI compared with 72% in control group (hazard ratio = 0.53; 95% confidence interval: 0.28-1.03; p = 0.06). The 2-year overall survival was 96% with adjuvant EGFR TKI and 90% in the group that did not receive TKI (hazard ratio: 0.62; 95% confidence interval: 0.26-1.51; p = 0.296).
  
  
  CONCLUSIONS
  Compared with patients who did not receive adjuvant TKI, we observed a trend toward improvement in DFS among individuals with resected stages I to III lung adenocarcinomas harboring mutations in EGFR exon 19 or 21 who received these agents as adjuvant therapy. Based on these data, 320 patients are needed for a randomized trial to prospectively validate this DFS benefit.
authors.affiliation: Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Weill Medical College of Cornell University, New York City, New York, USA.
authors.forename: Yelena Y
authors.initials: YY
authors.lastname: Janjigian
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Park
authors.forename: Maureen F
authors.initials: MF
authors.lastname: Zakowski
authors.forename: Marc
authors.initials: M
authors.lastname: Ladanyi
authors.forename: William
authors.initials: W
authors.lastname: Pao
authors.forename: Sandra P
authors.initials: SP
authors.lastname: D'Angelo
authors.forename: Mark G
authors.initials: MG
authors.lastname: Kris
authors.forename: Ronglai
authors.initials: R
authors.lastname: Shen
authors.forename: Junting
authors.initials: J
authors.lastname: Zheng
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Azzoli
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery; 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 / Q000601:surgery; D003131:Combined Modality Therapy; D004273:DNA, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D005091:Exons / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D011799:Quinazolines / Q000008:administration & dosage; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D004273:DNA, Neoplasm; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib