DR BEKAII-SAAB: Aflibercept, unlike bevacizumab, is not a monoclonal antibody. It actually is a VEGF Trap.
It acts to trap VEGF and binds to it, preventing it to bind to its receptor. Conceptually, it probably works about the same. You would expect a very similar anti-angiogenic benefit or effect. The toxicity profile is a bit different than bevacizumab.
There’s a higher likelihood of toxicity with aflibercept than with bevacizumab and noticeable toxicities, including increasing the risk of chemotherapy-induced toxicities. So, conceptually, it should work very similarly, but some of the pharmacodynamic effects actually end up being different.
DR LOVE: So it seems from what I could see in some of the diagrams, Alan, that were shown at ASCO, that it actually affects a different spectrum of VEGF isomers in bev.
DR VENOOK: It does, and it may also affect some other factors that are pertinent for tumor growth — PDGF, for example. I think it’s hard to distinguish from the other. The results actually look in parallel when you look at studies when they’re combined, although, as Tony said, there’s more toxicity in general, apparently, with aflibercept.
But again, distinguishing it from bevacizumab, I think, is not clear.
DR GOLDBERG: So Neil, I had 1 heartening and 1 disheartening thought about aflibercept. The heartening thought is that if you look at the TML study, we’re going to see that for bevacizumab added to second-line therapy, the response rate in second line was only 5%. But the response rate in the VELOUR study with aflibercept plus FOLFIRI was closer to 20%.
So that, to me, is heartening data.
The disheartening data is that almost about 30% of patients went off the VELOUR study, either because their doctors took them off or the patient asked to go off the study. And overall survival, that suggests to me that the toxicity profiles, when you stack bevacizumab up against aflibercept, will be in favor of bevacizumab.