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

<b>Background:</b> 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.<br/><b>Methods</b>: 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. <br/><b>Results</b>: 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 300mg/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. <br/><b>Conclusions</b>: 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.