title: Favorable clinical outcomes of pemetrexed treatment in anaplastic lymphoma kinase positive non-small-cell lung cancer.
abstract: BACKGROUND
  The development of anaplastic lymphoma kinase (ALK) inhibitor has just followed the recent discovery of ALK rearrangement in lung cancer, therefore not much is yet known about the clinical course and treatment outcomes to chemotherapy in ALK-positive patients. The purpose of this study was to investigate the clinical characteristics and treatment outcomes in patients with ALK-positive NSCLC treated with conventional chemotherapy during pre-ALK inhibitor period.
  
  
  METHODS
  We retrospectively screened 381 consecutive NSCLC patients without known epidermal growth factor receptor (EGFR) or KRAS mutation who were diagnosed between 2007 and 2008 at a single center, and identified ALK rearrangements by fluorescence in situ hybridization. Additional 44 ALK-positive patients who were identified since 2009 by central lab for participation on clinical trial were included for the analysis of clinical outcomes.
  
  
  RESULTS
  Of the 381 tumors screened, 21 (5.6%) showed ALK rearrangements, with twenty adenocarcinomas and one pleomorphic carcinoma. Of 65 ALK-positive patients including additional 44 ALK-positive patients, 32 patients received pemetrexed as a second- or further-line therapy, in whom the response rate was 34.4% (11/32), median progression-free survival (PFS) was 4.0 months (range: 0-22.0 months) and median overall survival (OS) was 50.8 months (95% confidence interval [CI]: 38.7-62.8).
  
  
  CONCLUSIONS
  The prevalence of ALK rearrangement was 5.6% among EGFR and/or KRAS wild-type/unknown NSCLC population. Pemetrexed, given as a second- or further-line therapy, showed favorable clinical outcomes in ALK-positive NSCLC patients.
authors.affiliation: Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Ha Yeon
authors.initials: HY
authors.lastname: Lee
authors.forename: Hee Kyung
authors.initials: HK
authors.lastname: Ahn
authors.forename: Ji Yun
authors.initials: JY
authors.lastname: Jeong
authors.forename: Mi Jung
authors.initials: MJ
authors.lastname: Kwon
authors.forename: Jung-Ho
authors.initials: JH
authors.lastname: Han
authors.forename: Jong-Mu
authors.initials: JM
authors.lastname: Sun
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Ahn
authors.forename: Keunchil
authors.initials: K
authors.lastname: Park
authors.forename: Yoon-La
authors.initials: YL
authors.lastname: Choi
authors.forename: Myung-Ju
authors.initials: MJ
authors.lastname: Ahn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D012189:Retrospective Studies; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins