title: Five-Year Survival in EGFR-Mutant Metastatic Lung Adenocarcinoma Treated with EGFR-TKIs.
abstract: BACKGROUND
  Activating mutations in the epidermal growth factor receptor gene (EGFR) predict for prolonged progression-free survival in patients with advanced non-small cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs) versus chemotherapy. Long-term survival outcomes, however, remain undefined. The objective of this study was to determine the 5-year survival in these patients and identify clinical factors associated with overall survival (OS).
  
  
  METHODS
  Patients with EGFR-mutant metastatic lung adenocarcinoma who had been treated with erlotinib or gefitinib at Dana-Farber Cancer Institute between 2002 and 2009 were included. OS was analyzed.
  
  
  RESULTS
  Among 137 patients, median progression-free survival and OS were 12.1 months (95% CI: 10.2-13.5) and 30.9 months (95% CI: 28.2-35.7), respectively. Twenty patients (14.6%) were 5-year survivors. In multivariate analysis, exon 19 deletions (hazard ratio [HR] = 0.63, 95% CI: 0.44-0.91, p = 0.01), absence of extrathoracic (HR = 0.62, 95% CI: 0.41-0.93, p = 0.02) or brain metastasis (HR = 0.48, 95% CI: 0.30-0.77, p = 0.002), and not a current smoker (HR = 0.23, 95% CI: 0.09-0.59, p = 0.002) were associated with prolonged OS. Age; sex; stage at diagnosis; liver, bone, or adrenal metastasis; specific TKI; and line of TKI therapy were not associated with OS.
  
  
  CONCLUSIONS
  Our data suggest that the rate of 5-year survival among patients with EGFR-mutant metastatic lung adenocarcinoma treated with erlotinib or gefitinib is 14.6%. Exon 19 deletions and absence of extrathoracic or brain metastasis are associated with prolonged survival. On the basis of our findings, clinicians can gain an enhanced estimation of long-term outcomes in this population.
authors.affiliation: Lowe Center for Thoracic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Lin
authors.affiliation: Lowe Center for Thoracic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Medicine, Rhode Island Hospital, Providence, Rhode Island.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Cardarella
authors.affiliation: Lowe Center for Thoracic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Lydon
authors.affiliation: Department of Biostatistics, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Dahlberg
authors.affiliation: Lowe Center for Thoracic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; Brigham and Women's Hospital, Boston, Massachusetts; Department of Medicine, Harvard Medical School, Boston, Massachusetts.
authors.forename: David M
authors.initials: DM
authors.lastname: Jackman
authors.affiliation: Lowe Center for Thoracic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; Brigham and Women's Hospital, Boston, Massachusetts; Department of Medicine, Harvard Medical School, Boston, Massachusetts.
authors.forename: Pasi A
authors.initials: PA
authors.lastname: Jänne
authors.affiliation: Lowe Center for Thoracic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; Brigham and Women's Hospital, Boston, Massachusetts; Department of Medicine, Harvard Medical School, Boston, Massachusetts. Electronic address: bejohnson@partners.org.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Johnson
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR; Non–small cell lung cancer; TKI; long-term survival