Sunitinib inhibits several receptor tyrosine kinases involved in cancer growth, metastasis, and neoangiogenesis, with its active metabolite (SU012662) demonstrating similar potency. In a randomized, double-blind, multinational, phase III trial, continuous treatment with oral sunitinib 37.5 mg/day significantly prolonged median progression-free survival time (primary endpoint) ≈2-fold relative to placebo in adults with locally advanced and/or metastatic, well differentiated pancreatic neuroendocrine tumors (pNETs). Sunitinib was also associated with a significantly greater objective tumor response rate than placebo, although limited data from an updated analysis demonstrated no significant difference between the treatments groups in terms of median overall survival. Continuous treatment with sunitinib generally had no detrimental effect on health-related quality of life and was generally well tolerated in patients with pNETs in this trial, with most adverse events being manageable and of grade 1 or 2 severity.