title: Subsequent chemotherapy improves survival outcome in advanced non-small-cell lung cancer with acquired tyrosine kinase inhibitor resistance.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) provide promising effect against non-small-cell lung cancer (NSCLC), although most tumors acquire resistance. Our objective was to assess the survival outcome of patients with NSCLC with or without subsequent chemotherapy after acquired TKI resistance.
  
  
  METHODS
  A total of 114 patients with pathologically confirmed stage IIIB or IV NSCLC who had had disease control with TKIs were retrospectively reviewed. After acquired TKI resistance, patients received either best supportive care (BSC) only or BSC plus subsequent chemotherapy. Both groups were well balanced in regard to performance status, age, sex, histology subtype, and smoking status.
  
  
  RESULTS
  Sixty-seven patients (58.8%) received subsequent chemotherapy, and 47 patients (41.2%) received BSC only. The median overall survival (OS) and progression-free survival (PFS) from the time of TKI resistance in the subsequent-chemotherapy group (11.2 months and 3.5 months, respectively) were longer than those of the BSC group (3.8 months and 1.5 months, respectively; P < .01). Patients who subsequently received taxane-based chemotherapy exhibited higher a response rate and disease control rate (48.7% and 79.5%, respectively) than patients treated with a nontaxane regimen (21.4% and 53.5%, respectively; P < .05). Overall survival and PFS in patients after taxane-based subsequent chemotherapy (12.7 months and 5.1 months, respectively) were longer than those of patients given a nontaxane regimen (7 months and 1.8 months, respectively; P < .01).
  
  
  CONCLUSIONS
  This study suggests that acquired TKI resistance should be managed aggressively. The higher antitumor response and survival outcome with a taxane-based regimen in this retrospective study could encourage further prospective investigation to confirm the efficacy of taxane over nontaxane chemotherapy in patients with NSCLC whose disease progresses with EGFR TKI treatment.
authors.affiliation: Department of Thoracic Medicine, Chang Gung Memorial Hospital, Chang Gung University, School of Medicine, Taipei, Taiwan.
authors.forename: Chih-Hsi
authors.initials: CH
authors.lastname: Kuo
authors.forename: Shu-Min
authors.initials: SM
authors.lastname: Lin
authors.forename: Kang-Yun
authors.initials: KY
authors.lastname: Lee
authors.forename: Fu-Tsai
authors.initials: FT
authors.lastname: Chung
authors.forename: Meng-Heng
authors.initials: MH
authors.lastname: Hsieh
authors.forename: Yueh-Fu
authors.initials: YF
authors.lastname: Fang
authors.forename: Chih-Ten
authors.initials: CT
authors.lastname: Yu
authors.forename: Han-Pin
authors.initials: HP
authors.lastname: Kuo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D016208:Databases, Factual; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D012189:Retrospective Studies; D015996:Survival Rate; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D043823:Taxoids