Patient Selection for Aflibercept in Advanced CRC

Transcript:Mark A. Socinski, MD: Speaking of GI tumors, one drug we haven’t talked a lot about is aflibercept. Could you give us the perspective from the GI world about the role this agent plays?

Manish A. Shah, MD: So, aflibercept is also known as VEGF-trap. It’s a combination antibody of VEGFR-1 and VEGFR-2. It’s a very novel ideal, and a great scientific discovery that you can sort of combine two receptors to create a drug to try to inhibit the pathway that these receptors would belong to. And it has activity, as was mentioned in the VELOUR study, in the second-line setting. It does improve chemotherapy versus chemotherapy alone in colon cancer. I think that one of the challenges with the drug is the increased toxicity. It not only inhibits VEGFA and VEGFB activity but also placental growth factor, and there are data that suggest that that actually may augment the diarrhea that’s seen with aflibercept. The challenge with that drug is that although it is an antiangiogenic agent, it isn’t similar to ramucirumab or bevacizumab in the fact that the toxicity spectrum is probably more so. And when you add it with chemotherapy, it magnifies the problem. So, I think for those reasons, it probably isn’t most commonly used as an antiangiogenic drug in colon cancer.

Mark A. Socinski, MD: I was going to say, you have a plethora of antiangiogenic agents in colon cancer. In the case of aflibercept, does that toxicity disadvantage—with an active drug—does it make you want to use it earlier in the course of therapy because you can use these others later when toxicity may be more of an issue, or is that really not even a thought process?

Johanna Bendell, MD: It was looked at in the first-line setting in a randomized phase II study. So, it was FOLFOX plus aflibercept versus FOLFOX alone, and that study didn’t really show us a benefit to using aflibercept there. Especially because when you think about colon cancer, the first-line patients are going to be on that regimen for 10 months to a year. And so we’ve started to modify these regimens for colon cancer patients more to ameliorate toxicity than to do the toxicity upfront when they’re still healthier. That’s the trend that’s been happening in colon cancer.

I think what happened with aflibercept is that when you have three different agents now that all show similar efficacy, the question becomes, what’s the toxicity and what’s the wallet toxicity? Certainly we’re in New York, and there was a lot of discussion about cost and cost control. And I think—and this is just my own take at market usage—what I see in patients coming in is that in the second-line setting, people tend to just stick with the bevacizumab because it’s what they’ve done, it’s been around the longest.

Occasionally you’ll see a ramucirumab patient or an aflibercept patient. For aflibercept, there’s one niche population where it seems to be used a little bit more—and I think reasonably so—which is in a patient with a KRAS-mutated colorectal who has very rapid progression in the first line, and you want to give them something in the second-line. Folks have used aflibercept there to say, well, do they need something a little bit more anti-angiogenesis? Now nobody’s proven that but that’s probably the niche population where you’ll see that used.

Mark A. Socinski, MD: Does there seem to be more activity in that population or hard to tell?

Johanna Bendell, MD: Not necessarily. I think this is more of a, ‘let’s try to use something different,’ and that population’s never been studied specifically.

Mark A. Socinski, MD: And of course in lung cancer, aflibercept had a negative trial and really never got any traction.

Roy S. Herbst, MD, PhD: Not at all. We’re very excited about the fact that we can measure, but not much at all, unfortunately.

Transcript Edited for Clarity