title: Meta-analysis of pemetrexed plus carboplatin doublet safety profile in first-line non-squamous non-small cell lung cancer studies.
abstract: OBJECTIVE
  This meta-analysis compared safety profiles (selected drug-related treatment-emergent adverse events [TEAEs]) of first-line pemetrexed plus carboplatin (PCb) area under the concentration-time curve 5 mg/min•mL (PCb5) or 6 mg/min•mL (PCb6), two widely used regimens in clinical practice for advanced non-squamous non-small cell lung cancer.
  
  
  METHODS
  All patients received pemetrexed 500 mg/m2every 21 days with either of two carboplatin doses for up to 4-6 cycles. Safety profiles of PCb doses were compared using three statistical analysis methods: frequency table analysis (FTA), generalized linear mixed effect model (GLMM), and the propensity score method. Efficacy outcomes of PCb5 and PCb6 regimens were summarized.
  
  
  RESULTS
  A total of 486 patients mainly from the US, Europe, and East Asia were included in the analysis; 22% (n = 105) received PCb5 in one trial and 78% (n = 381) received PCb6 in four trials. The FTA comparison demonstrated that PCb5 vs PCb6 was associated with a statistically significantly lower incidence of TEAEs, including all-grade thrombocytopenia, anemia, fatigue, and vomiting, and grade 3/4 thrombocytopenia. In the GLMM analysis, PCb5 patients were numerically less likely to experience all-grade and grade 3/4 neutropenia, anemia, and thrombocytopenia. The propensity score regression analysis showed PCb5 group patients were significantly less likely than PCb6 group patients to experience all-grade hematologic TEAEs and grade 3/4 thrombocytopenia and anemia. After applying propensity score 1:1 matching, FTA analysis showed that the PCb5 group had significantly less all-grade and grade 3/4 hematologic toxicities. Overall efficacy outcomes, including overall survival, progression-free survival, and response rate, were similar between the two carboplatin doses.
  
  
  CONCLUSIONS
  Acknowledging the limitations of this meta-analysis of five trials, heterogeneous in patient's characteristics and trial designs, the results show that the PCb5 regimen was generally associated with a better safety profile than PCb6 across three statistical approaches, with no apparent impact on survival outcomes.
authors.affiliation: a Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan.
authors.forename: Isamu
authors.initials: I
authors.lastname: Okamoto
authors.affiliation: b Hospital Martha-Maria Halle-Doelau , Halle , Germany.
authors.forename: Wolfgang H W
authors.initials: WH
authors.lastname: Schuette
authors.affiliation: c Duke University , Durham , NC , USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Stinchcombe
authors.affiliation: d IBCT - Instituto Brasileiro de Cancerologia Torácica , São Paulo , Brazil.
authors.forename: José
authors.initials: J
authors.lastname: Rodrigues-Pereira
authors.affiliation: e Eli Lilly and Company , Madrid , Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: San Antonio
authors.affiliation: f Eli Lilly and Company , Indianapolis , IN , USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: f Eli Lilly and Company , Indianapolis , IN , USA.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Liu
authors.affiliation: f Eli Lilly and Company , Indianapolis , IN , USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: John
authors.affiliation: g Thomas Jefferson University , Philadelphia , PA , USA.
authors.forename: Ralph G
authors.initials: RG
authors.lastname: Zinner
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D018572:Disease-Free Survival; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D000068437:Pemetrexed / Q000008:administration & dosage; D057216:Propensity Score
chemical_list: D000068437:Pemetrexed; D016190:Carboplatin
keywords: Pemetrexed; carboplatin; efficacy; non-squamous non-small cell lung cancer; safety