The Clinical Development of Vandetanib: Updates on Ongoing Phase III Clinical Trials in Advanced Non—Small-Cell Lung Cancer

Abstract

Vandetanib is a once-daily oral anticancer agent that selectively inhibits vascular endothelial growth factor—dependent tumor angiogenesis and epidermal growth factor receptor—dependent tumor cell proliferation and survival. In second/third—line NSCLC, significant improvements in progression-free survival (PFS) were observed in 2 phase II studies of vandetanib versus gefitinib (median PFS, 11.9 weeks vs. 8.1 weeks; hazard ratio [HR], 0.63; 1-sided P = .013) and docetaxel ± 100 or 300 mg vandetanib (median PFS, 18.7 weeks for vandetanib 100 mg plus docetaxel versus 12 weeks for docetaxel (HR, 0.64; 1-sided P = .037; for the 300-mg arm, HR, 0.83; P = .231). Higher objective response rates and disease control rates were also observed in the vandetanib arms, although overall survival was not significantly prolonged. In these studies, vandetanib has been generally well tolerated in clinical trials at daily doses of ≥ 300 mg, with common adverse events including rash, diarrhea, and QTc prolongation. Currently in NSCLC, 3 phase III registration trials have completed accrual, and 1 remains in progress. Each of these trials aims to further establish the efficacy and safety of vandetanib in the second/third—line setting (Table 1). Information on these studies, including their design, endpoints, and current status, will be presented. Ongoing work is also addressing the role of various biomarkers in the efficacy of vandetanib in NSCLC. Individualized treatment based on the presence of certain biomarkers might enhance efficacy of targeted therapies like vandetanib. A summary of planned biomarker analyses will also be presented.