title: The efficacy and safety of platinum plus gemcitabine (PG) chemotherapy with or without molecular targeted agent (MTA) in first-line treatment of non-small cell lung cancer (NSCLC).
abstract: BACKGROUND
  Trials investigating the efficacy and safety of combining molecular targeted agent (MTA) with platinum-gemcitabine (PG) in first-line treatment of advanced non-small cell lung cancer (NSCLC) have shown inconsistent findings. This meta-analysis aimed to explore whether the addition of MTAs to PG in NSCLC could provide a survival benefit with a tolerable toxicity.
  
  
  METHODS
  Web of knowledge, PubMed, Ovid, Embase, and Cochrane Library were searched to identify relevant studies and extract data on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and common grade 3 or 4 adverse events. Subgroup analyses were conducted on the basis of race and the type of MTA.
  
  
  RESULTS
  Twelve trials with a total of 6143 patients were included in this meta-analysis. Compared with PG chemotherapy, combination therapy of MTA with PG did not improve OS (hazard ratio [HR] = 0.96, 95% confidence interval [CI] = 0.90-1.01) but improved PFS (HR = 0.77, 95% CI = 0.66-0.89) and ORR (risk ratio [RR] = 1.33, 95% CI = 1.11-1.60). Subanalysis indicated that there was more incidence of grade 3 or 4 rash (RR = 11.20, 95% CI = 6.07-20.68), anemia (RR = 1.21, 95% CI = 1.01-1.46), diarrhea (RR = 2.62, 95% CI = 1.21-5.65), and anorexia (RR = 2.08, 95% CI = 1.12-3.88) in combining epidermal growth factor receptor targeted therapy group compared to PG group. An increased risk of grade 3 or 4 rash (RR = 5.08, 95% CI = 1.53-16.79), thrombocytopenia (RR = 1.50, 95% CI = 1.03-2.18), and hypertension (RR = 2.36, 95% CI = 1.05-5.32) was observed in sorafenib combination group.
  
  
  CONCLUSIONS
  The combination of PG plus MTA was superior to PG alone in terms of PFS and ORR but not in OS. The combination chemotherapy also showed a higher frequency of grade 3 or higher toxic effects in patients with advanced NSCLC than PG chemotherapy.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Southeast University, Nanjing, Jiangsu Department of Neurology, Shanghai General Hospital, Shanghai JiaoTong University, Shanghai Department of Neuropsychiatry, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
authors.forename: Jiaying
authors.initials: J
authors.lastname: Yang
authors.forename: Jieyu
authors.initials: J
authors.lastname: He
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
authors.forename: Taishun
authors.initials: T
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Luo
authors.forename: Pei
authors.initials: P
authors.lastname: Liu
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D024221:Antineoplastic Protocols; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D058990:Molecular Targeted Therapy / Q000009:adverse effects / Q000379:methods; D017671:Platinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D017671:Platinum Compounds; D003841:Deoxycytidine; C512478:EGFR protein, human; D066246:ErbB Receptors; D000093542:Gemcitabine