title: Comparative analyses of overall survival in patients with anaplastic lymphoma kinase-positive and matched wild-type advanced nonsmall cell lung cancer.
abstract: BACKGROUND
  The purpose of this study was to investigate the overall survival (OS) of patients with advanced ALK-positive nonsmall cell lung cancer (NSCLC) who were managed in the pre-ALK inhibitor era and to compare their survival with that of a matched case cohort of ALK wild-type (WT) patients.
  
  
  METHODS
  Data from 1166 patients who had stage IIIB/IV NSCLC with nonsquamous histology were collected from the NSCLC database of Seoul National University Hospital between 2003 and 2009. ALK fluorescence in situ hybridization (FISH) was used to analyze 262 patients who either had the WT epidermal growth factor receptor (EGFR) or were nonresponders to previous EGFR tyrosine kinase inhibitor (TKI) therapy. Overall survival (OS) was compared between 3 groups: 1) ALK-positive patients, 2) EGFR mutation-positive patients, and 3) ALK-WT/EGFR-WT patients. Progression-free survival (PFS) after first-line chemotherapy and EGFR TKIs also was analyzed.
  
  
  RESULTS
  Twenty-three patients were ALK-positive according to FISH analysis and did not receive ALK inhibitors during follow-up. The median OS for ALK-positive patients, EGFR mutation-positive patients, and WT/WT patients was 12.2 months, 29.6 months, and 19.3 months, respectively (vs EGFR mutation-positive patients, P = .001; vs WT/WT, P = .127). The PFS after first-line chemotherapy for the 3 groups was not different. However, the PFS for patients who received EGFR TKIs was shorter in ALK-positive patients compared with the other 2 groups (vs EGFR mutation-positive patients, P < .001; vs WT/WT, P < .021).
  
  
  CONCLUSIONS
  In the pre-ALK inhibitor era, ALK-positive patients experienced the shortest survival, although it did not differ statistically from that of WT/WT patients. Although their responses to platinum-based chemotherapy were not different from comparator groups, ALK-positive patients were even more resistant to EGFR TKI treatment than WT/WT patients.
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: June Koo
authors.initials: JK
authors.lastname: Lee
authors.forename: Heae Surng
authors.initials: HS
authors.lastname: Park
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Kim
authors.forename: Kimary
authors.initials: K
authors.lastname: Kulig
authors.forename: Tae Min
authors.initials: TM
authors.lastname: Kim
authors.forename: Se-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Yoon-Kyung
authors.initials: YK
authors.lastname: Jeon
authors.forename: Doo Hyun
authors.initials: DH
authors.lastname: Chung
authors.forename: Dae Seog
authors.initials: DS
authors.lastname: Heo
authors.forename: Woo-Ho
authors.initials: WH
authors.lastname: Kim
authors.forename: Yung-Jue
authors.initials: YJ
authors.lastname: Bang
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D016019:Survival Analysis
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases