Everolimus for Advanced Pancreatic Neuroendocrine Tumors

SUMMARY: Everolimus (AFINITOR®) is an oral mTOR (mammalian target of rapamycin) inhibitor, presently approved for the treatment of advanced renal cel carcinoma. Based on the established efficacy of AFINITOR® in phase II trials, a prospective, randomized, phase III study was conducted in which 410 patients with advanced, low grade or intermediate grade pancreatic neuroendocrine tumors with progression within the previous 12 months were randomized to receive AFINITOR®, at a dose of 10 mg QD (207 patients), or placebo (203 patients).The primary end point, progression free survival (PFS) was met, with a PFS of 11 months in the AFINITOR® group and 4.6 months in the placebo group. These benefits were accomplished with a low rate of grade III and IV toxicities. It appears that the mTOR pathway may play an important role in the molecular pathogenesis of pancreatic neuroendocrine tumors. N Engl J Med 2011; 364:514-523