title: Overall survival benefits for combining targeted therapy as second-line treatment for advanced non-small-cell-lung cancer: a meta-analysis of published data.
abstract: BACKGROUND
  Combining targeted therapy has been extensively investigated in previously treated advanced non-small-cell lung cancer (NSCLC), but it is still unclear whether combining targeted therapy might offer any benefits against standard monotherapy with erlotinib. We thus performed a meta-analysis of randomized controlled trials to compare the efficacy and safety of combining targeted therapy versus erlotinib alone as second-line treatment for advanced NSCLC.
  
  
  METHODS
  Several databases were searched, including Pubmed, Embase and Cochrane databases. The endpoints were overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and grade 3 or 4 adverse event (AEs). The pooled hazard ratio (HR) or odds ratio (OR), and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials.
  
  
  RESULTS
  Eight eligible trials involved 2417 patients were ultimately identified. The intention to treatment (ITT) analysis demonstrated that combining targeted therapy significantly improved OS (HR 0.90, 95% CI: 0.82-0.99, p = 0.024), PFS (HR 0.83, 95% CI: 0.72-0.97, p = 0.018), and ORR (OR 1.35, 95% CI 1.01-1.80, P = 0.04). Sub-group analysis based on phases of trials, EGFR-status and KRAS status also showed that there was a tendency to improve PFS and OS in combining targeted therapy, except that PFS for patients with EGFR-mutation or wild type KRAS favored erlotinib monotherapy. Additionally, more incidence of grade 3 or 4 rash, fatigue and hypertension were observed in combining targeted therapy.
  
  
  CONCLUSIONS
  With the available evidence, combining targeted therapy seems superior over erlotinib monotherapy as second-line treatment for advanced NSCLC. More studies are still needed to identify patients who will most likely benefit from the appropriate combining targeted therapy.
authors: Department of Oncology, the Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors: Wei-Xiang
authors: WX
authors: Qi
authors: Qiong
authors: Q
authors: Wang
authors: Yan-Ling
authors: YL
authors: Jiang
authors: Yuan-Jue
authors: YJ
authors: Sun
authors: Li-Na
authors: LN
authors: Tang
authors: Ai-Na
authors: AN
authors: He
authors: Da-Liu
authors: DL
authors: Min
authors: Feng
authors: F
authors: Lin
authors: Zan
authors: Z
authors: Shen
authors: Yang
authors: Y
authors: Yao
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000628:therapy*; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy*; D016019:Survival Analysis