The role of vandetanib in the second-line treatment for advanced non-small-cell-lung cancer: a meta-analysis of four randomized controlled trials

Lung. 2011 Dec;189(6):437-43. doi: 10.1007/s00408-011-9332-1. Epub 2011 Oct 11.

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.

Publication types

  • Meta-Analysis

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Middle Aged
  • Piperidines / adverse effects
  • Piperidines / therapeutic use*
  • Quinazolines / adverse effects
  • Quinazolines / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Survival Rate
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Piperidines
  • Quinazolines
  • vandetanib