title: The role of vandetanib in the second-line treatment for advanced non-small-cell-lung cancer: a meta-analysis of four randomized controlled trials.
abstract: BACKGROUND
  The purpose of this study was to assess the efficacy and toxicity of vandetanib in the second-line treatment for advanced non-small cell lung cancer (NSCLC).
  
  
  METHODS
  We systematically searched for randomized clinical trials that compared therapy with vandetanib versus standard second-line treatment, including docetaxel, pemetrexed, erlotinib, or gefitinib, as second-line treatment for patients with histologically proven non-small-cell lung cancer. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival, overall response rate, and grade 3 or 4 toxicity. Data were extracted from the studies by two independent reviewers. The meta-analysis was performed by Stata version 10.0 software (Stata Corporation, College Station, TX, USA).
  
  
  RESULTS
  Four randomized clinical trials (N = 3,292 patients) were eligible. Meta-analysis showed that there was significant improvement in PFS (hazards ration (HR), 0.91; 95% confidence interval (CI), 0.83-1.00; P = 0.039) and overall response rate (relative risk (RR), 1.49; 95% CI, 1.04-2.14; P = 0.03) in therapy with vandetanib group compared with standard second-line therapy group, although the pooled HR for overall survival (HR, 0.95; 95% CI, 0.88-1.03; P = 0.191) showed no significant difference between the two groups. In addition, there were less incidences of grade 3 or 4 anemia (RR, 0.39; 95% CI, 0.22-0.67; P = 0.001) in therapy with vandetanib group. With regard to the risk of grade 3 or 4 neutropenia (RR, 1.19; 95% CI, 1.0-1.43; P = 0.054), diarrhea (RR, 1.38; 95% CI, 1.0-1.94; P = 0.059), nausea and vomiting (RR, 0.77; 95% CI, 0.48-1.26; P = 0.308), rash (RR, 2.83; 95% CI, 0.73-10.9; P = 0.131), cough (RR, 1.19; 95% CI, 1.0-1.43; P = 0.054), and fatigue (RR, 1.0; 95% CI, 0.747-1.35; P = 0.971), there was no significant difference between the two groups.
  
  
  CONCLUSIONS
  Therapy with vandetanib offered a clinically meaningful and statistically significant improvement in PFS and ORR in patients with advanced NSCLC but did not benefit overall survival. Therapy with vandetanib regimens might be suggested as second-line treatment for advanced NSCLC based on a similar toxicity profile compared with standard second-line therapy.
authors: Department of Oncology, The Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, 200233, China.
authors: Wei-Xiang
authors: WX
authors: Qi
authors: Li-Na
authors: LN
authors: Tang
authors: Ai-Na
authors: AN
authors: He
authors: Zan
authors: Z
authors: Shen
authors: Yang
authors: Y
authors: Yao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010880:Piperidines; D011799:Quinazolines; C452423:vandetanib