title: Overall response to first-line tyrosine kinase inhibitor and second-line chemotherapy is predictive of survival outcome in epidermal growth factor receptor-mutated adenocarcinoma.
abstract: BACKGROUND
  First-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective for the treatment of lung adenocarcinoma with an EGFR-sensitizing mutation, but resistance is inevitable. Chemotherapy is widely used in the second-line setting. The outcome following this treatment scheme has not been thoroughly evaluated.
  
  
  METHODS
  From 2007 to 2011, consecutive patients with mutated EGFR receiving first-line TKI and second-line chemotherapy were retrospectively reviewed. The overall response was categorized into double responder, single responder and double nonresponder.
  
  
  RESULTS
  Following this treatment scheme, baseline Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (HR 0.60; 95% CI 0.37-0.98; p = 0.041) and double responder (HR 0.24; 95% CI 0.07-0.78; p = 0.018) were independent predictors of overall survival. Absence of pleural metastasis independently predicted the response to first-line TKI (OR 2.60; 95% CI 1.13-5.99; p = 0.025). In TKI responders, ECOG performance status 0-1 before chemotherapy (OR 4.95; 95% CI 1.15-21.28; p = 0.006), an exon 19 deletion (OR 4.74; 95% CI 1.30-17.21; p = 0.018) and progression-free survival (PFS) on first-line TKI (OR 1.02; 95% CI 1.01-1.09; p = 0.049) independently predicted the response to second-line chemotherapy. A moderate linear relationship (Pearson's r = 0.441; p = 0.001) existed between the PFS of this treatment scheme in TKI responders.
  
  
  CONCLUSIONS
  The status of double responder to first-line TKI and second-line chemotherapy was predictive of improved survival in EGFR-mutated adenocarcinoma.
authors: Scott Chih-Hsi
authors: SC
authors: Kuo
authors: Ping-Chih
authors: PC
authors: Hsu
authors: Chih-Hung
authors: CH
authors: Chen
authors: Chih-Teng
authors: CT
authors: Yu
authors: Chih-Liang
authors: CL
authors: Wang
authors: Fu-Tsai
authors: FT
authors: Chung
authors: Shu-Min
authors: SM
authors: Lin
authors: Yu-Lun
authors: YL
authors: Lo
authors: Tse-Ching
authors: TC
authors: Chen
authors: Chien-Ying
authors: CY
authors: Liu
authors: Cheng-Ta
authors: CT
authors: Yang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality*; D000077192:Adenocarcinoma of Lung; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D012189:Retrospective Studies; D017384:Sequence Deletion / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases