Therapeutic Options in Newly Diagnosed mRCC

Toni Choueiri, MD:I think this is going to be a very important question. Nivolumab/ipilimumab hands-down beat the TKI sunitinib with an overall survival benefit. But there are many considerations. First and foremost are the toxicities and how practitioners are going to be familiar with managing immune-related adverse events. Second, the regimen has shown the activity mostly in intermediate and poor risk. Actually, if you look at the small group of patients with good-risk disease, responses and progression-free survival seem to favor sunitinib. Third, and most important—something we tend to forget about—is that immuno-oncology drugs now are given intravenously, whereas the TKIs are oral. So, there is a patient preference here between visiting the hospital and not visiting the hospital as frequently for the infusion.

So, it’s actually an evolving story, too. What I think is going to happen, rather than a TKI versus an I-O, is that there will be, in the next few years, several combination TKIs plus I-Os and that we need to figure out how to use them. Because, fortunately or not fortunately, all these combinations from phase III well-powered trials were compared against sunitinib and are not compared against each other. So, I think this is, again, an evolving story, and, hopefully, I’ll be here in the next few years to discuss these results.

The combination of bevacizumab/interferon showed activity in the frontline setting some time ago versus interferon, which we don’t use now. That combination doesn’t have any advantage currently over what we use in frontline studies. And we do not actually use it much.

Now, temsirolimus is a drug that showed activity against cytokines in patients with poor-risk renal cell cancer. I think the schedule of temsirolimus intravenous weekly and the fact that, overall in an indirect comparison, mTOR inhibitors usually have not fared as well as VEGF TKIs dampen our enthusiasm for using temsirolimus.

Transcript edited for clarity.