title: Non-platinum doublets were as effective as platinum-based doublets for chemotherapy-naïve advanced non-small-cell lung cancer in the era of third-generation agents.
abstract: OBJECTIVE
  The aim was to compare the efficacy between doublets of third-generation agents (non-platinum) and doublets of platinum plus a third-generation agent (platinum-based) for chemotherapy-naïve advanced non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  We conducted a literature-based meta-analysis to compare the efficacy between doublets of third-generation agents and doublets of platinum plus a third-generation agent for chemotherapy-naïve advanced NSCLC. The primary end point was overall survival, and the secondary end points were progression-free survival (PFS) and response rate. Subgroup analyses were also conducted by different non-platinum doublet regimens or different platinum-based doublets. A descriptive review for toxicity was performed.
  
  
  RESULTS
  Sixteen randomized controlled trials were identified ultimately. Results demonstrated that the efficacy of non-platinum doublets was comparable with platinum-based doublets according to the overall survival (HR = 1.03, 95 % CI = 0.98-1.08, p = 0.29). Subgroup analyses by different non-platinum doublets also showed the efficacy of all the third-generation doublets, such as vinorelbine plus gemcitabine, vinorelbine plus paclitaxel, gemcitabine plus paclitaxel, and gemcitabine plus docetaxel, was comparable with platinum-based doublets (HR = 1.00, 95 % CI = 0.78-1.27, p = 0.98; HR = 0.97, 95 % CI = 0.80-1.18, p = 0.79; HR = 1.05, 95 % CI = 0.99-1.12, p = 0.11; HR = 1.01, 95 % CI = 0.92-1.10, p = 0.87; respectively). Subgroup analyses by different platinum-based doublets indicated that the efficacy of the third-generation doublets were equal to both cisplatin-based doublets and carboplatin-based doublets (HR = 1.08, 95 % CI = 1.00-1.17, p = 0.05; HR = 1.00, 95 % CI = 0.94-1.05, p = 0.94; respectively). The secondary end points indicated that platinum-based doublets might have an advantage in PFS but not in response rate (HR = 1.06, 95 % CI = 1.01-1.12, p = 0.03; RR = 0.99, 95 % CI = 0.90-1.08, p = 0.81; respectively).
  
  
  CONCLUSIONS
  Non-platinum doublets were as effective as platinum-based doublets with different toxicity profile for chemotherapy-naïve advanced NSCLC in the era of third-generation agents.
authors.affiliation: Department of Oncology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Jiang
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Liang
authors.forename: Xinli
authors.initials: X
authors.lastname: Zhou
authors.forename: Ruofan
authors.initials: R
authors.lastname: Huang
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Chu
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhan
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D002986:Clinical Trials as Topic / Q000592:standards; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D000077143:Docetaxel; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016017:Odds Ratio; D017239:Paclitaxel / Q000008:administration & dosage; D017671:Platinum Compounds / Q000008:administration & dosage*; D017594:Publication Bias; D058028:Research Report / Q000592:standards; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D017671:Platinum Compounds; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D014747:Vinblastine; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin; D000077235:Vinorelbine; D000093542:Gemcitabine