DR BENDELL: This was interesting, because as I read the abstract I laughed to myself, because this has happened in my clinic more than one time. And so what this is, is looking at dosing of octreotide LAR in patients with neuroendocrine tumors, both carcinoids and PNETs. And so when you look at the FDA guidelines, the dosing is supposed to be between 10 and 40 mg every 4 weeks. And so often we see patients or people using higher doses in their patients. And so they looked at what the frequency of higher doses is, and they saw, actually, a significant percent of people within these NCCN institutions were using much higher doses of octreotide LAR than the recommended doses.

And most often it was for either symptom control or tumor progression. But I think what you’re seeing here is one, people aren’t afraid of using octreotide LAR. People aren’t afraid of going up in dosing. And people were either giving the regular doses, which are either 20 or 30 mg more often, as often as every other week, or they do 60 mg every 4 weeks. But I think what it also shows us is that kind of lack of other treatment options that people believe in for this disease.

Where they’re more likely to try to bump up on a relatively benign therapy than try to move into something else for these folks.

DR LOVE: How about this SWOG study? It seems like there are a number of trials in GI NET looking at bevacizumab. And this is one of them. What about this study and the rationale?

DR BENDELL: Right. So we’ve seen that not only PNET, where we have approval of an anti-angiogenic agent, but we’ve also seen that carcinoids seem to be very vascular tumors as well. And so looking at anti-angiogenic agents for these patients makes a lot of sense. I know folks at Charlie’s institution have done — Matt Kulke has done quite a bit of work looking at anti-angiogenic agents for carcinoid tumors. This study, unfortunately, has taken too long to accrue, and now we’re waiting for the data from it. This is the problem with neuroendocrine studies, is that the patients live so long that it takes forever to get the results of the data. But I think this is a very eagerly anticipated study, where they’re looking at octreotide plus interferon versus octreotide plus bevacizumab for these patients.

DR LOVE: So Randy, Johanna mentioned — I think it’s the CALGB study that Matt Kulke actually, I think, is the PI on, looking at bevacizumab, this with everolimus. Can you talk about that paper as well as the Phase II study looking at cape/temozolomide and bev?

DR HECHT: One thing that’s just to start out with that’s interesting, that this SWOG trial also has interferon, which I think — no one is using interferon. But that was a theoretical anti-angiogenic agent. And also, there was a little bit of data with that. So we talked briefly before that while other than the positive PROMID trial in midgut tumors, there really aren’t — the studies have been negative, unfortunately, with carcinoid, which is the vast majority of the NETs that we see.

That being said, the smaller subgroup of pancreatic neuroendocrine tumors had 2 drugs approved relatively recently: one, everolimus, the other one, sunitinib, both of which were relatively small trials but had actually very similar data with a benefit in outcome. And so the CALGB trial is interesting, and it makes sense, since everolimus is an FDA-approved drug for this indication to try to mix and match the various pathways that are affected. Presumably, sunitinib works by affecting angiogenesis, though we don’t know if that’s the only way that it works.

By combining bevacizumab, which also has activity in neuroendocrine tumors together with everolimus, and I think this is a reasonable study that — the hardest part is, is just that there’s just not as many pancreatic neuroendocrine tumors and, if you have a hard time accruing to carcinoid patients, maybe it was the interferon. It’s only a randomized Phase II. I hope that they’re able to accrue without being a pharmaceutical trial. But I hope so.

The second one is, is that we have 2 drugs that are approved, but we don’t really talk as much about cytotoxic agents. Cytotoxic agents in carcinoid, there may be a little bit of benefit, but you go back to streptozotocin, going back a long time ago, and clearly some neuroendocrine tumors would benefit from those, though it’s extremely difficult to give. But there are institutions — perhaps your institution. I don’t know if you use streptozotocin. I know MD Anderson uses it a lot with multidrug therapy. But the toxicity has been very difficult.

That being said, there are other cytotoxics that have a much better profile. And there was a Phase II trial by Strosberg of capecitabine and temozolomide, which is an alkylating agent that’s approved in CNS tumors with an extraordinarily high response rate. And not just high response rate, but, unlike the biological agents we were talking about before, but durable responses. I think median PFS was 2 years, if I remember correctly. And I have used this in my clinic and seen almost exactly that, with them falling off at about 2 years, with excellent response rates. So I think I said that it was approximately 70%. So this is an interesting trial.

So you have fairly well tolerated, that combination of cape and temozolomide. And then adding another well-tolerated drug, an anti-angiogenic drug, I think is actually a very interesting study.

Colorectal cancer

Gastric cancer

Pancreatic cancer

Hepatocellular carcinoma

Gastrointestinal neuroendocrine tumors

Gastrointestinal stromal tumors