title: Erlotinib-based targeted dual agent versus erlotinib alone in previously treated advanced non-small-cell lung cancer: a meta-analysis of 13 randomized controlled trials.
abstract: To compare the effects of an erlotinib-based targeted dual agent with erlotinib alone in previously treated patients with advanced non-small lung cancer (NSCLC).
  
  
  
  The PubMed and Embase databases and the Cochrane Central Register of Controlled Trials were searched for publications between January 2005 and March 2016. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CIs were derived. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity were assessed.
  
  
  
  Thirteen trials with a total of 4509 patients were included in this meta-analysis. Compared with erlotinib alone, combination therapy showed no improvement in OS (HR = 0.95; 95% CI, 0.89-1.02; P = .132) though significantly prolonged PFS (HR = 0.82; 95% CI, 0.75-0.90; P < .001). Combination therapy significantly increased ORR (RR = 1.32; 95% CI, 1.09-1.60; P = .005) and DCR (RR = 1.26; 95% CI, 1.17-1.36, P < .001). Sub-analysis assessment failed to identify any sub-groups which could benefit from combination therapy in terms of OS. Combination therapy was associated with more grade 3 or higher toxic effects (RR = 1.54; 95% CI, 1.22-1.95; P < .001). Patients treated with combination therapy had more grade 3 or greater fatigue (RR = 1.49; 95% CI, 1.16-1.91; P = .002), but did not develop more diarrhea (RR = 2.02; 95% CI, 0.86-4.77; P = .107) or rash (RR = 1.29, 95% CI, 0.90-1.85; P = .172). This study had limitations about heterogeneities among the included trials, and the analysis was not based on individual patient data.
  
  
  
  Compared with erlotinib alone, the erlotinib-based targeted dual agent showed a minimal magnitude of improvement in PFS but did not improve OS. The role of erlotinib-based combinations in previously treated patients with NSCLC seemed insignificant.
authors.affiliation: a Department of Medical Oncology , Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-sen University , Shantou , Guangdong , China.
authors.forename: Shuhan
authors.initials: S
authors.lastname: Yu
authors.affiliation: b Department of Respiratory Medical Oncology , Cancer Hospital of Shantou University Medical College , Shantou , Guangdong , China.
authors.forename: Qini
authors.initials: Q
authors.lastname: Xu
authors.affiliation: c Department of Nursing , Cancer Hospital of Shantou University Medical College , Shantou , Guangdong , China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: a Department of Medical Oncology , Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-sen University , Shantou , Guangdong , China.
authors.forename: Xuyuan
authors.initials: X
authors.lastname: Li
authors.affiliation: d Department of Medical Oncology , First affiliated Hospital of Shantou University Medical College , Shantou , Guangdong , China.
authors.forename: Haoquan
authors.initials: H
authors.lastname: Cai
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000401:mortality; D018572:Disease-Free Survival; D000069347:Erlotinib Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality; D016032:Randomized Controlled Trials as Topic
chemical_list: D000970:Antineoplastic Agents; D000069347:Erlotinib Hydrochloride
keywords: Advanced non-small-cell lung cancer; Efficacy; Erlotinib; Meta-analysis; Targeted therapy