DR KULKE: There are 2 big categories you need to think about with neuroendocrine tumors. In the past, we had really lumped all of these patients together whether they had carcinoid or pancreatic neuroendocrine tumors. So one really big point that has become very, very clear is that these are 2 different diseases, and drugs probably work somewhat differently between the 2. So that’s one really important point to distinguish and one that’s relatively easy to make.
The somewhat more complex one, and I think an area that’s still in evolution, is the histologic classification of these tumors. And there are probably 4 or 5 different histologic classifications that are out there. They’re very confusing.
In a very general way, I think you can categorize these patients into 2 main groups: there are those who have the more indolent, well-differentiated tumors and then those who have the very aggressive, poorly differentiated tumors.
DR LOVE: Emily, any thoughts in terms of pancreatic neuroendocrine tumors in terms of how you think through the sequence of systemic therapy?
DR BERGSLAND: I think it’s really on a case-by-case basis, depending on the extent of disease and the symptoms that a patient might have. Certainly, for people with functional tumors octreotide is often used just to help control the hormone-mediated symptoms. Chemotherapy, I think, still has a role. I think we’ve struggled to define the ideal chemotherapy, but I think in somebody with bulky disease that’s symptomatic or rapidly growing there’s a role for chemotherapy, and then certainly now we have 2 new approved targeted agents, everolimus and sunitinib, that both delay progression.
At this point, we don’t have enough information to really know in which order they should be used. And so I think they’re both viewed as viable options and the choice of the drug depends a lot on the patients’ comorbidities, whether they have uncontrolled diabetes, for example, in which case everolimus may be a less ideal choice, or if they have uncontrolled hypertension sunitinib might be a less ideal choice.
DR LOVE: So Rich, what are your thoughts on this? And in terms of the issue of chemotherapy, what kind of chemotherapy?
DR GOLDBERG: I do use chemotherapy, certainly in the high-grade tumors right away and generally treat them like a small cell with either a taxane or etoposide and a platinum. On the other end of the spectrum, I agree with Emily that chemotherapy should play a role in some point in many of these patients’ management.
FOLFOX is predictable and relatively well tolerated and does seem to be active in neuroendocrine tumors. It’s certainly easier to use than the old regimens from my mentor, Chuck Mortell, with streptozocin and dacarbazine. So I think it’s more or less replacing those. Irinotecan is also active in some cases. So that’s what I tend to use.
DR LOVE: So Matt, can you dissect out for us a little bit more about everolimus and sunitinib in pancreatic NET and carcinoid?
DR KULKE: So we have 2 randomized studies in pancreatic NET that are really quite definitive. Both of these agents are clearly active in pancreatic neuroendocrine tumors and both, as we know, were approved. So it’s fantastic that we have those options.
In carcinoid it is a little bit trickier. And I think in many ways in the RADIANT-2 study we’re really learning how to do studies in this disease. Large studies hadn’t been previously done, and there were some issues. One is the issue of how to define progression, and the other is the imbalance in prognostic factors, one of which was the chromogranin A. So I think in carcinoid these studies probably still need to be done. There is a RADIANT-4 study ongoing right now. That will look at everolimus, again in carcinoid, and hopefully also some ongoing studies, one being led by Dr Bergsland, looking at tyrosine kinase inhibitors in carcinoid.