title: Survival Benefit of Pemetrexed in Lung Adenocarcinoma Patients With Anaplastic Lymphoma Kinase Gene Rearrangements.
abstract: BACKGROUND
  There have been conflicting findings regarding the efficacy of pemetrexed for lung cancer with anaplastic lymphoma kinase (ALK) rearrangement. This study was conducted to explore the benefits of pemetrexed in this patient group.
  
  
  METHODS
  Among patients who had received pemetrexed therapy between January 2010 and March 2014 for advanced stage lung adenocarcinoma, cases were selected with a confirmed ALK rearrangement, epidermal growth factor receptor (EGFR) mutation, or Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation. Clinical outcomes resulting from the pemetrexed-based regimen were analyzed according to the genetic alteration.
  
  
  RESULTS
  A total of 442 patients were enrolled, including 52 with ALK translocation, 188 with EGFR mutation, 34 with KRAS mutation, and 168 wild type patients. The mean age was 57 ± 11 years and women were predominant in the ALK-positive and EGFR mutant groups. Pemetrexed-platinum combination therapy was usually performed as first-line therapy, whereas pemetrexed monotherapy was usually used as second-line therapy and beyond. The response rate (RR) was greater in the ALK-positive group than in the other groups (26.9% vs. 12.8%, 8.8%, and 18.5%; P = .046). The median progression-free survival (PFS) of ALK-positive patients was longer than that of the others (7.8 months vs. 2.5, 2.3, and 2.9 months; P < .001). This benefit on survival was more evident when pemetrexed was used as a single agent (P < .001).
  
  
  CONCLUSIONS
  ALK-positive patients showed a greater RR and longer PFS with pemetrexed-based therapy than patients without ALK rearrangements, suggesting that pemetrexed should be preferentially considered for the treatment of ALK-positive lung adenocarcinoma when use of crizotinib is not feasible.
authors: Department of Pulmonary and Critical Care Medicine, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, South Korea.
authors: Sojung
authors: S
authors: Park
authors: Department of Pulmonary and Critical Care Medicine, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, South Korea.
authors: Tai Sun
authors: TS
authors: Park
authors: Department of Pulmonary and Critical Care Medicine, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, South Korea; Department of Oncology, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, South Korea.
authors: Chang-Min
authors: CM
authors: Choi
authors: Department of Oncology, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, South Korea.
authors: Dae Ho
authors: DH
authors: Lee
authors: Department of Oncology, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, South Korea.
authors: Sang-We
authors: SW
authors: Kim
authors: Department of Oncology, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, South Korea.
authors: Jung-Shin
authors: JS
authors: Lee
authors: Department of Pulmonary and Critical Care Medicine, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, South Korea.
authors: Woo Sung
authors: WS
authors: Kim
authors: Department of Pathology, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, South Korea.
authors: Joon Seon
authors: JS
authors: Song
authors: Department of Oncology, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, South Korea. Electronic address: jclee@amc.seoul.kr.
authors: Jae Cheol
authors: JC
authors: Lee
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000068437:Pemetrexed / Q000008:administration & dosage / Q000627:therapeutic use*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C117307:KRAS protein, human; D000068437:Pemetrexed; C000626173:ALK protein, human; C000626175:Alk protein, rat; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Anaplastic lymphoma kinase; Lung cancer; Pemetrexed; Progression-free survival