Ulka Vaishampayan, MD: For patients who are not eligible for frontline I/O [immuno-oncology] therapy, what factors into your decision for choosing a VEGF TKI [tyrosine kinase inhibitor]? It’s typically about 25% of our patients, I think.

Rana R. McKay, MD: There are a lot of factors that come into play when selecting frontline therapy for any given patient, and in particular, when selecting a VEGF inhibitor as opposed to an I/O-I/O or I/O-VEGF combination. The most commonly utilized criteria for selection right now are the IMDC [International Metastatic RCC Database Consortium] criteria. The data support the role of VEGF inhibition in those who have favorable-risk disease. And data that were presented by David McDermott, MD, based on a study looking at atezolizumab and bevacizumab in patients with metastatic RCC [renal cell carcinoma] demonstrate that patient population—favorable-risk patients—tends to have a signature of angiogenesis.

I think other things that come into play are actually sites of metastases, particularly for patients who have bone metastases. The frontline study of CABOSUN that was conducted by Toni Choueiri, MD, demonstrated a superiority of cabozantinib over sunitinib. Now, that was predominantly done in intermediate- and poor-risk patients, but the bone-predominant patients seem to really derive benefit from the cabozantinib. And so that can be considered based on site of disease.

Additionally, I think patient factors come into play. Do they have contraindications for I/O therapy? Are they on steroids to treat some underlying medical condition? Do they have an underlying autoimmune disease? We still don’t know the role of I/O therapies from any prospective data in the context of people who have psoriasis or other immune conditions that may be well managed, where they’re not on systemic steroids or other anti-immune agents. I think those are the predominate factors that come into play.

We spoke a little during our Twitter chat on biomarkers and what the appropriate biomarker is. There isn’t a biomarker at the present time to help with selection of a VEGF inhibitor in the frontline space. I think another thing to consider is histology. That plays into effect. If you have a papillary tumor, for example, or papillary RCC, maybe you’re going to want to use a MET inhibitor—cabozantinib—in that individual. Or maybe the lack of sarcomatoid differentiation may…those patients tend to do better with I/O therapy. That could potentially be informative in regard to patient selection. But I think this is still evolving. Barring the IMDC, we haven’t specifically conducted prospective studies carving out based on a biomarker or selecting out a unique patient population.

Ulka Vaishampayan, MD: The data for cabozantinib are in intermediate- and poor-risk disease, but the FDA approval is across the board. In favorable-risk patients, are you guys considering this agent in the frontline setting?

Rana R. McKay, MD: The discussion around favorable risk is the longest discussion that you have with your patient. It’s those favorable-risk patients who are really going to do well with just about anything you treat them with. Tian had talked about the various treatment options—from observation all the way to doublet therapy—that you could introduce. You could potentially make the case that if somebody has oligometastatic bone metastases, they may benefit from being on cabozantinib. It’s not enough that you’re going to radiate all the spots, but you can put them on the VEGF TKI. So I think you can make a case for a specific patient.

Transcript Edited for Clarity