Treatment Landscape of Advanced Renal Cell Carcinoma

Sumanta K. Pal, MD: It's amazing. Things have changed so much over a relatively short span of time. When I started in the field over a decade ago, the conversations we were having centered on whether to use a VEGF [vascular endothelial growth factor] inhibitor; mTOR [mammalian target of rapamycin] inhibitors came along thereafter. Now the conversations have gotten a lot more sophisticated. We’re typically considering combinations of VEGF inhibitors with immune-oncology [IO] therapy up front. In the current landscape, the options include a pure checkpoint inhibitor regimen of nivolumab with ipilimumab; axitinib with pembrolizumab. A targeted therapy and immunotherapy regimen is also an option. I suspect that we'll soon have the option of using cabozantinib with nivolumab in the frontline setting too.

A lot of people may ask what the utility is in having another VEGF plus IO regimen. To that, I would say that the data for cabozantinib with nivolumab speak for themselves. I would suggest that the progression-free survival benefit that we're seeing, which is roughly 8 months to 16 months by independent review, and a progression-free survival of 19 months with the combination of cabozantinib with nivolumab represents the high watermark. The other element of the data that stands out is the fact that about 5% of patients have primary progressive disease.

This means that only 1 in 20 patients is not going to derive clinical benefit from this regimen. Again, that's a far cry from the data that we saw a decade ago when all we had was targeted therapy. I would also suggest that the real standout in this data set comes from quality of life. When you look at the data with the 40-mg dose of cabozantinib plus nivolumab, you see a trend toward improvement in quality of life through the course of the study. That's something that we're not seeing with the other targeted therapy regimens.

Transcript Edited for Clarity