title: Pemetrexed Singlet Versus Nonpemetrexed-Based Platinum Doublet as Second-Line Chemotherapy after First-Line Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor Failure in Non-small Cell Lung Cancer Patients with EGFR Mutations.
abstract: OBJECTIVE
  Platinum-based doublet chemotherapy is the treatment of choice for patients with non-small cell lung cancer (NSCLC); however, the role of a platinum-based doublet as second-line therapy after failure of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for NSCLC patients has not yet been elucidated. The purpose of this study was to compare the clinical efficacy of pemetrexed versus a platinum-based doublet as second-line therapy after failure of EGFR TKI used as first-line therapy for NSCLC patients with EGFR mutations.
  
  
  METHODS
  We designed a multicenter retrospective cohort study of 314 NSCLC patients with EGFR mutations who received an EGFR TKI as first-line palliative chemotherapy. Our analysis included 83 patients who failed EGFR TKI therapy and received second-line cytotoxic chemotherapy.
  
  
  RESULTS
  Forty-six patients were treated using a platinum-based doublet and 37 patients were treated using singlet pemetrexed. The overall response rates of patients receiving a platinum-based doublet and patients receiving pemetrexed were17.4% and 32.4%, respectively (p=0.111). The median progression-free survival (PFS) of patients receiving pemetrexed was significantly longer than that of patients receiving a platinum-based doublet (4.2 months vs. 2.7 months, respectively; p=0.008). The hazard ratio was 0.54 (95% confidence interval, 0.34 to 0.86; p=0.009).
  
  
  CONCLUSIONS
  Our retrospective analysis found that second-line pemetrexed singlet therapy provided significantly prolonged PFS compared to second-line platinum-based doublet chemotherapy for NSCLC patients with EGFR mutations who failed first-line EGFR TKI. Conduct of prospective studies for confirmation of our results is warranted.
authors: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors: Sehhoon
authors: S
authors: Park
authors: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors: Bhumsuk
authors: B
authors: Keam
authors: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors: Se Hyun
authors: SH
authors: Kim
authors: Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.
authors: Ki Hwan
authors: KH
authors: Kim
authors: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors: Yu Jung
authors: YJ
authors: Kim
authors: Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.
authors: Jin-Soo
authors: JS
authors: Kim
authors: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors: Tae Min
authors: TM
authors: Kim
authors: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors: Se-Hoon
authors: SH
authors: Lee
authors: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors: Dong-Wan
authors: DW
authors: Kim
authors: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors: Jong Seok
authors: JS
authors: Lee
authors: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors: Dae Seog
authors: DS
authors: Heo
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000068437:Pemetrexed / Q000494:pharmacology* / Q000627:therapeutic use; D010984:Platinum / Q000494:pharmacology* / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D012189:Retrospective Studies; D017211:Treatment Failure
chemical_list: D047428:Protein Kinase Inhibitors; D000068437:Pemetrexed; D010984:Platinum; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Epidermal growth factor receptor; Non-small-cell lung carcinoma; Pemetrexed; Platinum