Tian Zhang, MD: Dr Bilen, can you tell us what factors you take into consideration and how do you distinguish between the combinations when you’re choosing frontline therapy for patients with advanced clear cell RCC [renal cell carcinoma]?

Mehmet A. Bilen, MD: Thank you very much. I think this is a very, very, very important question. Like when we see someone with newly diagnosed renal cell carcinoma and we are about to start treatment, and I am sure all of us going through those discussions since we have at least 4 very effective regimen in our toolbox. I think those clinic visits tend to be longer and longer each year because we need to cover all these important data and then make a final decision. If I can summarize and simplify, I think the first thing in our mind, is this a patient we want to use IO/IO [immuno-oncology], which is nivo + ipi [nivolumab plus ipilimumab], or IO [immuno-oncology]/VEGF [vascular endothelial growth factor]? We have 3 different options that we highlighted earlier. I think manufacturers are affecting our decision since we don’t have any validated biomarkers and predictive biomarker. Hope in the near future, we have a clear validated predictive biomarker, and our job is going to be much easier. But at this point, 2022, I think we still going to go with the clinical features. I think first thing is the patient’s overall situation, which I think is the frailty-like status. Is not only age but I think several factors can affect the frailty. I think this is very important, especially for VEGF/TKI [tyrosine kinase inhibitor]. If someone is very frail, they tend to have more difficulty for VEGF/TKI. I think other factors are such as cardiac issues. If someone has significant heart failure, arrhythmia, poorly controlled hypertension, then [they] might not be a good candidate for VEGF/TKI. If someone has a new blood clot or active bleeding, again, we may not want to use a VEGF-based combination. I think IO/IO might be a better way. If someone has a recent surgery or going to have surgery in the near future that we worry about the wound healing, then we may choose IO/IO versus IO/VEGF. Again, multiple clinical things can affect our final decision versus if someone has what I call smoldering autoimmune disease that we know is not absolute contraindication, but we also don’t want to flare-up. This might be a sort of mild rheumatoid arthritis or other things that we still can use single-agent IO, but we worry about the IO doublet. I think at that point we may choose IO/VEGF than IO/IO combination. Concerning IMDC [International Metastatic RCC Database Consortium] risk group, again, there is a lot of debate, but still based on the FDA [Food and Drug Administration] approval or NCCN [National Comprehensive Cancer Network] recommendation, we need to factor in the IMDC risk group. I think this might be important for insurance approval also. We know that IO/VEGF combinations are approved all risk group, including favorable, intermediate poor risk versus nivolumab/ipilimumab is only approved for intermediate and poor risk. I think at the end of the day, this is the only risk group that we use in our clinical practice. In addition to that, histology is important. Based on CheckMate 214, sarcomatoid patients have very good outcome for nivo [nivolumab]/ipi [ipilimumab]. If someone with sarcomatoid histology, I prefer that combination. Also, site of metastasis can play a role. If someone with multiple mets [metastases], including liver and bone, that we have 1 chance, 1 opportunity, and want to use our regimen that give us the rapid and deep response, I think the IO/VEGF combination seems to give us a better response rate. This is something I use at that time. Again, hopefully in the near future, we are going to have a validated biomarker and that will guide us more like objective.

Tian Zhang, MD: I think we’re all looking forward to that point where we can use potentially molecular biomarkers and markers beyond the clinical risk stratification to help select treatments for the right patient.

This transcript has been edited for clarity.