title: Efficacy and safety of vandetanib, a dual VEGFR and EGFR inhibitor, in advanced non-small-cell lung cancer: a systematic review and meta-analysis.
abstract: BACKGROUND
  Vandetanib, an oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling, has attracted wide interest in treatment of advanced non-small-cell lung cancer (NSCLC). We aimed to assess its efficacy and safety via a systematic review and meta-analysis.
  
  
  METHODS
  Trials comparing vandetanib-based therapy and non-vandetanib therapy for advanced NSCLC were identified. Endpoints evaluated were progression-free survival (PFS), overall survival (OS), objective tumor response rate (ORR), and toxicity.
  
  
  RESULTS
  Seven trials including 4,492 patients were included in the analysis. As compared with placebo, vandetanib yielded a clear benefit for ORR (odds ratio (OR) = 2.04; 95% CI, 1.60-2.61; P <0.001), and a clinically and statistically significant 25% improvement in PFS (hazard ratio (HR) = 0.75; 95% CI, 0.66- 0.85; P < 0.001). However, these benefits did not translate into a significant improvement in OS (HR = 0.95; 95% CI, 0.88-1.04; P = 0.291). Subgroup analyses showed that vandetanib 100mg/d was associated with greater antitumor activity than 300 mg/d when given in combination with chemotherapy. In addition, the pooled results demonstrated no statistically significant difference between vandetanib and single-targeted agents in PFS, ORR or OS. Vandetanib was associated with more frequent adverse events.
  
  
  CONCLUSIONS
  Vandetanib, as compared with placebo, significantly increases ORR and PFS, but does not improve OS in the treatment of advanced NSCLC. As compared with single-targeted agent, vandetanib does not provide any efficacy advantage. Furthermore grade 3 or greater toxicity proved greater in the vandetanib arm.
authors.affiliation: Department of Health Statistics, Second Military Medical University, Shanghai, China.
authors.forename: Xinji
authors.initials: X
authors.lastname: Zhang
authors.forename: Yingyi
authors.initials: Y
authors.lastname: Qin
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Chong
authors.initials: C
authors.lastname: Bai
authors.forename: Tianyi
authors.initials: T
authors.lastname: Zhu
authors.forename: Jinfang
authors.initials: J
authors.lastname: Xu
authors.forename: Cheng
authors.initials: C
authors.lastname: Wu
authors.forename: Mengjie
authors.initials: M
authors.lastname: Wu
authors.forename: Chaoxiang
authors.initials: C
authors.lastname: Wang
authors.forename: Hualing
authors.initials: H
authors.lastname: Song
authors.forename: Lixin
authors.initials: L
authors.lastname: Wei
authors.forename: Jia
authors.initials: J
authors.lastname: He
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D010880:Piperidines; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D040262:Receptors, Vascular Endothelial Growth Factor; C452423:vandetanib