DR BENDELL: The TRIBE trial was a randomized Phase III study that was looking at FOLFOXIRI plus bev versus FOLFIRI plus bev. And so this is building on a trial that was performed years ago of FOLFOXIRI versus FOLFIRI. So now we’re adding in a biologic. And I thought what was really interesting once the FOLFOXIRI data came out is, if you polled all of us and we said, “Who’s using FOLFOXIRI? It’s got a great response rate, getting people to resection,” and everybody agrees with the data, and then you say, “Who uses it?” And nobody raises their hand.

But I think now that we’re using FOLFIRINOX in pancreatic cancer, people are becoming a little less shy of the FOLFOXIRI regimen, which is even gentler than FOLFIRINOX.

And as one would expect, the FOLFOXIRI plus bev regimen did show an improvement in response rate, 65 versus 55%. It showed an improvement in progression-free survival, about 12 versus 10 months. And very interestingly, a little bit of a trend toward improvement in overall survival, though the data is very, very early. What was also nice about this study is that they only gave a maximum of 6 months of these intense regimens, and then patients were changed over to a 5-FU/bevacizumab maintenance therapy. So if you’re going to give patients very intensive therapy, you stop it after a certain amount of time.

DR LOVE: So you mentioned that the dosing was not as intense as in the FOLFIRINOX regimen. Were you able to tell — I mean, indirectly — in terms of toxicity?

DR BENDELL: Yes. So you could see more toxicity with the FOLFOXIRI/bev regimen than the FOLFIRI/bev. It was a little bit more neutropenia, a little bit more mucositis, diarrhea, neuropathy, as one would expect, but there certainly weren’t more febrile neutropenia events. There weren’t any more SAE events between the 2 arms. So it looks like even though there was more toxicity, it was relatively handleable. There were some more dose reductions in the FOLFOXIRI arm, as well.

DR LOVE: So maybe, again, the situation and, as we talked about, maybe it’s not that common, but certainly from a theoretical point of view, people are interested when you need a response.

DR BENDELL: Exactly.

DR LOVE: We did a poll of some investigators in the program we’re doing currently. And we saw that after ASCO, particularly because of this presentation, a number of people had shifted toward this regimen when they need a response, for example, for, again, shrinkage of hepatic mets. What was your reaction? Did it change the way you practice?

DR BENDELL: It did. It gave me more inclination, again, as you said, to, if I need a response, to use the FOLFOXIRI regimen with bev. It was also very interesting — I know we’ll talk about this patient population soon — but they showed a subset analysis of BRAF-mutated patients. Though the numbers were low, very interestingly the patients with a BRAF mutation tended to do a bit better with the FOLFOXIRI regimen compared to the FOLFIRI regimen. Again, small patient numbers, small patient population, but very intriguing data.

DR LOVE: Have you used this regimen?

DR BENDELL: Yes. Yes.

DR LOVE: And what’s your experience with the toxicity?

DR BENDELL: It’s actually been fairly well tolerated. You do have to watch out for neutropenia. I don’t tend to give prophylactic growth factors when I use this, though I do when I use FOLFIRINOX. But I think that as long as you keep an eye on those patients — you want a little bit more of a hearty patient that you’re going to give this regimen to, rather than potentially somebody with a lot of comorbidities.

DR LOVE: So anyone have a different view of this in terms of — it sounds like you feel this is tolerable and maybe you’re going to think about it more when you need a response. Charlie, you agree?

DR FUCHS: I think it is tolerable. The only caveat is: Often the reason we want to get a very good response is to get them to resection of a liver met. And it’s important to realize within the trial, they didn’t show that patients randomized to the regimen had a higher rate of liver resections. So they didn’t achieve that endpoint. Admittedly, they may not have had enough patients to test that hypothesis. But they didn’t prove it. So if you’re betting on this regimen getting your patient to a liver resection, the trial didn’t show it.

Colorectal cancer

Gastric cancer

Pancreatic cancer

Hepatocellular carcinoma

Gastrointestinal neuroendocrine tumors

Gastrointestinal stromal tumors