Role of everolimus in pancreatic neuroendocrine tumors.

Survival from pancreatic neuroendocrine tumors has not improved over the past two decades and, until recently, streptozocin was the last therapeutic agent approved for this malignancy. Everolimus blocks mTOR, which plays an integral role in cell growth, mitosis and angiogenesis. Abnormal PI3K-Akt/PKB-mTOR pathway signaling has been implicated in the pathogenesis of pancreatic neuroendocrine tumors. In a Phase III study, patients with low- and intermediate-grade advanced pancreatic neuroendocrine tumors were randomized to receive everolimus 10 mg/day or placebo. Median progression-free survival was significantly greater in patients treated with everolimus than placebo - 11 versus 4.6 months - and drug-related adverse events were consistent with the known side-effect profile of everolimus. Everolimus represents a significant treatment development for pancreatic neuroendocrine tumors.