Promising Anti-VEGF Combinations for NSCLC

Transcript:Marina Garassino, MD: There are at least 2 important strategies of combining antiangiogenics with other drugs, excluding chemotherapy. The first one, I think, is in EGFR-mutated patients because in this case, we achieved great results with the combination of erlotinib and bevacizumab, and we are waiting for the final results. But there are also ongoing trials with erlotinib and ramucirumab in the same setting, in a trial called RELAY. And there is another area, in my opinion, that is worth investigating, and this is combining antiangiogenics with immunotherapy. There are several hypotheses and rational ideas on combining them. One is that antiangiogenics can increase the permeability of the vessels, and this can allow the T cells to reach the tumor. The other possibility is that the antiangiogenics can enhance the expression of the antigens on the dendritic cells, and so allow more activity of immunotherapy. So, I think that those in this field will have a lot of work to do because it is possible that the 2 strategies are synergistic.

Roy S. Herbst, MD, PhD: The field of antiangiogenic agents is sort of slow right now. I don’t see too many new agents coming forward. At one time, this was all the rage: targeting the blood vessels and preventing tumor growth. I think their greatest utility now of bevacizumab, ramucirumab, and other agents is going to be how they modify the microenvironment; how it affects immune function and infiltration of T cells, the so-called TIL (tumor infiltrating lymphocytes); and how it affects the flow of blood into the tumor, the migration of macrophages, and other important constituents of the immune response. So, that’s where I would see things going. I don’t see these agents moving into the frontline unless they’re in the frontline with immunotherapy.

Enriqueta Felip, MD, PhD: There is a rationale to combine antiangiogenic agents plus immunotherapy. There are some studies suggesting that targeted agents may induce some immune effect in cancer. And there are other preclinical studies showing synergy between antiangiogenic drugs and immune checkpoint inhibitors, mainly anti-PD-1 and anti-PD-L1 strategies. And we have ongoing studies. There are phase I trials analyzing the combination of ramucirumab plus pembrolizumab, and there is also another phase I trial analyzing the combination of atezolizumab plus bevacizumab.

So, in lung cancer, there is a clear rationale to combine an antiangiogenic drug plus an anti—PD-1 or anti–PD-L1 compound. There are some studies showing synergy between the 2 strategies. And we also have the studies showing that targeted agents induced immune effects in cancer cells. There are ongoing studies. We will see the results of a combination of ramucirumab plus pembrolizumab and also the combination of atezolizumab plus bevacizumab.

Transcript Edited for Clarity