Although their occurrence is rare, pancreatic neuroendocrine tumors (NET) are difficult to treat. By the time of diagnosis, most patients have advanced metastatic disease and their 5-year survival rate is below 43%. The only chemotherapeutic agent approved for treating NET—streptozocin, either alone or in combination with doxorubicin—has limited benefit for such advanced cases. Now, two new studies offer some optimism. Two phase III multicenter, double-blind, randomized, placebo-controlled trials have indicated that the drug sunitinib, an inhibitor of multiple tyrosine kinases, and everolimus, an inhibitor of mTOR, are effective against advanced pancreatic NET, even in patients in whom other treatments have failed.

In a trial of 171 patients, sunitinib increased disease-free survival from 5.5 months to 11.4 months compared with placebo. Similarly, in a trial of 410 patients, everolimus improved progression-free survival from 4.6 months to 11 months. The authors estimated that 34% of patients treated with everolimus were alive and progression free at 18 months, compared with 9% who had received placebo. Based on these results and those of earlier trials, the FDA has granted everolimus priority review designation for the application of advanced NET. In October 2010, the FDA granted accelerated approval to everolimus for treatment of subependymal giant-cell astrocytomas associated with the autosomal dominant disorder tuberous sclerosis, and data from trials in breast cancer are expected at the end of this year. Everolimus was originally approved in March 2009 for the treatment of adults with advanced renal cell carcinoma whose disease was resistant to sunitinib or sorafenib.