title: Determinants of survival in advanced non--small-cell lung cancer in the era of targeted therapies.
abstract: BACKGROUND
  Molecular profiling of non-small-cell lung cancer (NSCLC) samples has a profound impact on choice of therapy. However, it is less clear whether EGFR and KRAS mutations are prognostic outside of a trial-based treatment paradigm.
  
  
  METHODS
  We performed a retrospective chart review of 513 patients with NSCLC undergoing EGFR and KRAS mutational analysis at the Hospital of the University of Pennsylvania between May 2008 and November 2011. Survival analysis was based on the 376 patients who received systemic treatment, and their survival was determined from the date of initiation of systemic therapy.
  
  
  RESULTS
  The median overall survival (OS) was 30.8 months (95% confidence interval [CI], 24.7-36.9). Neither EGFR mutational status (P = .09) nor KRAS mutational status (0.69) was associated with OS. Female sex (P < .001), never smoker status (P = .01), better performance status (PS) (P < .001), lower Charlson Comorbidity Index (P < .001), and lower age-weighted index (P < .001) were associated with prolonged survival. The presence of bone metastases (P = .001) and liver metastases (P = .004) was also associated with a shortened survival. In a multivariable regression that adjusted for stage, we demonstrated that male gender (P = .002), worse Eastern Cooperative Oncology Group PS (P = .01), metastases to bone (P = .03), and higher age-weighted comorbidity index (P = .001) were independent prognostic factors for shorter survival. EGFR mutation status was not prognostic (P = .85).
  
  
  CONCLUSIONS
  In our series, EGFR and KRAS do not function as prognostic determinants for NSCLC.
authors.affiliation: Abramson Cancer Center, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. joshua.bauml@uphs.upenn.edu
authors.forename: Joshua
authors.initials: J
authors.lastname: Bauml
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Mick
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Watt
authors.forename: Anil
authors.initials: A
authors.lastname: Vachani
authors.forename: Charu
authors.initials: C
authors.lastname: Aggarwal
authors.forename: Tracey
authors.initials: T
authors.lastname: Evans
authors.forename: Corey
authors.initials: C
authors.lastname: Langer
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics*; D001859:Bone Neoplasms / Q000235:genetics / Q000401:mortality / Q000556:secondary; D001932:Brain Neoplasms / Q000235:genetics / Q000401:mortality / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D058990:Molecular Targeted Therapy; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D015996:Survival Rate; D018631:ras Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: EGFR; KRAS; Non–small-cell lung cancer; Prognosis