Vandetanib (100 mg) in patients with locally advanced or metastatic hereditary medullary thyroid cancer

Abstract

Purpose: Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor tyrosine kinases that also inhibits rearranged during transfection kinase activity. Vandetanib (300 mg/d) has previously demonstrated antitumor activity in patients with advanced hereditary medullary thyroid cancer (MTC). This study investigated the efficacy and safety of 100 mg/d vandetanib in patients with advanced hereditary MTC.

Patients and methods: Eligible patients with unresectable, measurable, locally advanced, or metastatic hereditary MTC received 100 mg/d vandetanib. Upon disease progression, eligible patients could enter postprogression treatment with 300 mg/d vandetanib until a withdrawal criterion was met. The primary objective was to assess the objective response rate by response evaluation criteria in solid tumors.

Results: The study comprised 19 patients (13 males, six females; mean age 45 yr). Confirmed objective partial responses were observed in three patients, yielding an objective response rate of 16% (95% confidence interval 3.4-39.6). Stable disease lasting 24 wk or longer was reported in a further 10 patients (53%); the disease control rate was therefore 68% (95% confidence interval 43.4-87.4). Serum levels of calcitonin and carcinoembryonic antigen showed a sustained 50% or greater decrease from baseline in 16% (three of 19) and 5% (one of 19) of patients, respectively. Adverse events were predominantly grade 1 or 2 and consistent with previous vandetanib monotherapy studies.

Conclusions: Vandetanib at a once-daily dose of 100 mg has clinically relevant antitumor activity in patients with locally advanced or metastatic hereditary MTC and an overall acceptable safety profile.

Figure 1

Maximum reduction from baseline (or smallest increase from baseline for patients with no reductions) in target lesion size. Baseline radiographic measurements of target lesions were compared with measurements over the course of the study to determine the best change in target lesion size for each patient with data; one nonevaluable patient is not shown. Each bar represents one patient. The dashed line represents the threshold for partial response. *, Four patients with a best response of 0% change from baseline (all stable disease ≥24 wk).

Figure 2

Serum CTN levels [percent change from baseline (BL)] in patients with a best objective response (RECIST) of partial response (n = 3) (A), stable disease (n = 12) (B), and progressive disease (n = 3) (C).