Treating pancreatic neuroendocrine tumors

Two great articles in the New England Journal of Medicine offer hope to those who live with pancreatic neuroendocrine tumors (PNET). And not one, but two articles in NEJM for PNET; not bad at all! As a GI oncologist, I see a lot of these patients, and it is a welcome relief to have more in our arsenal for them; but, it’s equally as important to have published data that will compel outside payers to cover the costs of these oral chemotherapies. PNET patients tend to have slow-growing tumors that can grow over many years, and have, historically, been very refractory to standard chemotherapy. It has been noted in phase-1 and -2 studies, however, that prolonged responses were seen with agents that targeted VEGF or mTOR pathways.

One study, by Raymond and colleagues, looked at sunitinib for PNET, and found that sunitinib improved PFS (11.4 vs 5.5 months) over placebo. OS was looked at by a HR for death, since these patients live such a long period of time with their disease, rather than analyzing the more traditional (but much less practical) median survival. Indeed, the HR for death while on sunitinib was 0.41. RECIST response rate also favored sunitinib. Pretty much a homerun in terms of study outcomes!

The second study, by Yao and colleagues, looked at everolimus, which is an mTOR inhibitor, vs. placebo for PNET in what was known as the RADIANT-3 study. Open-label cross-over was allowed per protocol. Again, PFS was improved with everolimus, though OS was not different, perhaps representing a crossover effect. All subgroups seemed to benefit from everolimus, as well. So, now the question becomes, "which drug to choose first?" I am also left wondering what do to for my non-pancreatic low-grade neuroendocrine tumor patients, as well.