title: Reduced chemotherapy sensitivity in EGFR-mutant lung cancer patient with frontline EGFR tyrosine kinase inhibitor.
abstract: OBJECTIVE
  Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are a standard first-line treatment for EGFR-mutant patients with non-small cell lung cancer (NSCLC). However, it remains unclear whether frontline EGFR TKIs affect subsequent chemo-sensitivity in EGFR-mutant patients. This study compared chemo-sensitivity in patients treated with post-TKI chemotherapy and first-line chemotherapy controls.
  
  
  METHODS
  This study included 203 EGFR-mutant patients. The study group contained 68 patients treated with chemotherapy after first-line EGFR-TKI and the control group contained 135 patients who received first-line chemotherapy. The response rate (RR), progression-free survival (PFS) and overall survival (OS) were assessed.
  
  
  RESULTS
  In study group, the RR of chemotherapy was 13.2% compared with 34.1% in the control group (P=0.002). The median PFS of chemotherapy in the control group was significantly longer than in the study group (6.9 vs. 3.9 months, P<0.001), while the RR (76.5% vs. 68.9%, P=0.259) and PFS (11.0 vs. 10.2 months) of EGFR-TKI were similar between first- and second-line treatment. Cox regression analyses indicated that prior EGFR-TKI treatment had a higher risk for disease progression during chemotherapy treatment [hazard ratio (HR)=3.06; 95% CI=2.12-4.42, P<0.001]. Median overall survival was 31.7 months in the control group and 23.5 months in the study group (P<0.001). The adjusted HR for death in the study group was 1.91 (95% CI=1.33-2.76; P<0.001).
  
  
  CONCLUSIONS
  In EGFR-mutant patients, frontline EGFR-TKI significantly reduced the sensitivity of subsequent chemotherapy compared with that of TKI-naïve frontline chemotherapy. These findings need to be validated in further randomized trials.
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China; Division of Thoracic Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
authors.forename: Hong-hong
authors.initials: HH
authors.lastname: Yan
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
authors.forename: Xu-chao
authors.initials: XC
authors.lastname: Zhang
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
authors.forename: Wen-zhao
authors.initials: WZ
authors.lastname: Zhong
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
authors.forename: Yan-yan
authors.initials: YY
authors.lastname: He
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
authors.forename: Jin-lin
authors.initials: JL
authors.lastname: Guan
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
authors.forename: Fei-yu
authors.initials: FY
authors.lastname: Niu
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
authors.forename: Yi-sheng
authors.initials: YS
authors.lastname: Huang
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
authors.forename: Chong-rui
authors.initials: CR
authors.lastname: Xu
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
authors.forename: Song
authors.initials: S
authors.lastname: Dong
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China. Electronic address: syylwu@live.cn.
authors.forename: Yi-long
authors.initials: YL
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016022:Case-Control Studies; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors
keywords: Chemotherapy; Epidermal growth factor receptor; Non-small-cell lung cancer; Sensitivity; Tyrosine kinase inhibitors; first-line