Anti-VEGF/Immunotherapy Combinations in Kidney Cancer
Insights From: Martin H. Voss, MD, Memorial Sloan Kettering Cancer Center; Thomas Hutson, DO, PharmD, FACP, Baylor University Medical Center; Texas Oncology; James J. Hsieh, MD, PhD, Washington University School of Medicine
Martin H. Voss, MD: We have several combinations testing with immunotherapy plus targeted therapeutics, such as a VEGF receptor TKI, under investigation presently. And that goes back to the fact that many of the medications we already have on the market that are nonimmunotherapeutics, by principle, are hypothesized to have some form of a modulatory effect on the microenvironment, including the immune microenvironment of tumor cells.
So, the thought here is that by giving immunotherapy together with one of the approved nonimmunotherapy medications, we can somehow manipulate the immune microenvironment to be more susceptible to checkpoint inhibition. That is being tested by many investigators and multiple industrial sponsors presently, and we are starting to see early data that are very promising.
Thomas Hutson, DO, PharmD, FACP: At ASCO 2017, we saw the results of the IMmotion150 trial, which randomized patients with metastatic RCC, a total of 300, into 1 of 3 arms: atezolizumab alone, atezolizumab/bevacizumab, or to sunitinib as the standard arm. In this trial, we saw that the combination atezolizumab/bevacizumab produced a PFS of 11.7 months, not statistically significant over the sunitinib arm. However, in the PD-L1–positive group, patients had a PFS of approximately 14.7 months, which was a primary take-home message from this trial.
This phase II study showed a benefit to the combination of atezolizumab/bevacizumab over sunitinib, particularly in patients that were PD-L1–positive. That is going to be a strategy that is going to move forward in phase III study.
James J. Hsieh, MD, PhD: The IMmotion150 trial is, I think, the trial that actually changed the way we think how to combine targeted therapy and immunotherapy. So, the trial was started by Roche about 3 years ago, and I put a few patients of mine on the trial. And this is when I witnessed firsthand the difference that I can give my patients. I have a patient who came in with a chest tube. We removed the chest tube, gave him his combination. His lung disease disappeared, but his big kidney tumor is still there. So, we take out the kidney tumor. And now 2 years later, we take all the drugs away and he has been disease-free for 1 year.
That’s actually the very first one to inform me that that combination is the way to go. So, this is where the IMmotion150 trial starts. But the IMmotion150 trial has a drawback. Avastin is very easy to combine. The problem is Avastin cannot be used for a long time, especially in kidney cancer patients because most of them develop proteinuria. And you have to take them off treatment, and they now become a patient on single-agent monotherapy. That’s why Avastin (bevacizumab)/atezolizumab was very, very good. It educated us that this is the direction we go. But whether it is the best combination, I think that is very individualized. That’s why everybody was moving toward different kinds of combinations.