title: Clinical effectiveness and clinical toxicity associated with platinum-based doublets in the first-line setting for advanced non-squamous non-small cell lung cancer in Chinese patients: a retrospective cohort study.
abstract: BACKGROUND
  Real-world evidence lacks for clinical effectiveness and clinical toxicity associated with platinum-based doublets in the first-line setting for advanced non-squamous non-small cell lung cancer (advNS-NSCLC) in Chinese patients.
  
  
  METHODS
  Patients receiving first-line chemotherapy for advNS-NSCLC in four Chinese tertiary care hospitals from 2007 to 2012 were retrospectively identified for chart review. Propensity score methods created best matched pairs for platinum/pemetrexed versus other platinum-based doublets for head-to-head comparisons of early treatment discontinuation (completed treatment cycles <4), treatment failure (progressive disease or early treatment discontinuation), and adverse events (AE). Conventional multiple logistic regression analyses were also performed to confirm the impact of the studied platinum-based doublets on early treatment discontinuation, treatment failure, and hematological AE using vinorelbine/platinum as reference.
  
  
  RESULTS
  1,846 patients were included to create propensity score matched treatment groups for platinum/pemetrexed versus docetaxel (95 pairs), paclitaxel (118 pairs), gemcitabine (199 pairs), and vinorelbine (72 pairs)-contained doublet, respectively. Platinum/pemetrexed was associated with significantly lower risks of early treatment discontinuation (odds ratio (OR) ranged from 0.239, p = 0.001 relative to platinum/docetaxel to 0.389, p = 0.003 relative to platinum/paclitaxel) and treatment failure (OR ranged from 0.257, p < 0.001 relative to platinum/paclitaxel to 0.381, p < 0.001 relative to platinum/gemcitabine) than the other four studied doublets. Platinum/pemetrexed was also associated with several significantly lower hematological AE rates, such as versus platinum/paclitaxel (any hematological AE: OR 0.508, p = 0.032), platinum/gemcitabine (i.e., any hematological AE: OR 0.383, p < 0.001; anemia: OR 0.357, p < 0.001; thrombocytopenia: OR 0.345, p < 0.001) or platinum/vinorelbine (i.e., neutropenia: OR 0.360, p = 0.046; anemia: OR 0.181, p = 0.014) in matched patients. Further conventional logistic regression analyses indicated that pemetrexed/platinum was ranked lowest for the risks of early treatment discontinuation (OR 0.326, p < 0.001), treatment failure (OR 0.460, p < 0.001), and any hematological AE (OR 0.329, p < 0.001).
  
  
  CONCLUSIONS
  Pemetrexed plus platinum had significantly superior clinical effectiveness as compared to the other platinum-based doublets with third-generation cytotoxic agents and was also associated with several lower hematological toxicity rates than gemcitabine or vinorelbine-based doublet in the first-line setting for advNS-NSCLC in Chinese patients.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Chen
authors.forename: Shengqi
authors.initials: S
authors.lastname: Wu
authors.forename: Chenping
authors.initials: C
authors.lastname: Hu
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Wang
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Yang
authors.forename: Narayan
authors.initials: N
authors.lastname: Rajan
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.forename: Zhuanzhuan
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Division of Social and Administrative Pharmacy, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada. wendong.chen@utoronto.ca.
authors.forename: Wendong
authors.initials: W
authors.lastname: Chen
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology*; D002681:China; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D016017:Odds Ratio; D010984:Platinum / Q000008:administration & dosage; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D010984:Platinum