Drs. Brian Rini and Monty Pal Debate Frontline RCC Treatment Options

By Brian Rini, MD, FASCO, Monty Pal, MD - Last Updated: March 14, 2023

In a debate series between Brian Rini, MD, and Monty Pal, MD, they discuss frontline RCC treatment options and whether an individualized versus one-size-fits-all approach is best.

Dr. Rini: We’re going to talk today about several different areas of kidney cancer. We’re going to start with a debate around frontline treatments and an individualized approach versus a one-size-fits-all approach. Then we’ll go into some other topics, including clinical trials and adjuvant therapy.

I’m going to open by talking about frontline therapy and kidney cancer. As everybody knows, there are 4 immune-based doublets that are standard of care that have all shown improved survival: ipilimumab/nivolumab, and then the 3 immuno-oncology(IO)/tyrosine kinase inhibitor (TKI) doublets. I would argue that each of them has unique strengths and weaknesses. If you look at the IO/TKI regimens, they have quite obviously different TKIs and different dosing strategies. Lenvatinib had a very high dose, cabozantinib had a somewhat middle dose of 40 mg, and axitinib had a middle dose of 5 mg BID [twice daily] with titration.

I think in terms of the TKI part of that, using those regimens allows you to differentially dose the TKI. For instance, I tend to use lenvatinib/pembrolizumab but understand that 20 mg of lenvatinib is a lot for patients who tend to use axitinib/pembrolizumab in a more frail population. Ipilimumab/nivolumab has its strengths. The tail of the curve I think is probably a strength, and certainly in sarcomatoid. There’s really good data for sarcomatoid histology being a nice biomarker for ipilimumab/nivolumab response with complete response rates that were almost 25% in that analysis of CheckMate-214. I think there are differences among the regimens, and I think there is some role for individualizing therapy.

Dr. Pal: That’s a really interesting take on it, Brian. I often think of the practical circumstance that patients in the community face. Most oncologists are seeing maybe 2 to 3 patients with kidney cancer a year. Looking to some of the nuances of the data I think is a little bit challenging. I’ve heard folks say, I’ll go with lenvatinib/pembrolizumab if I want to get a higher response rate, and I’ll go with ipilimumab/nivolumab if I feel like I have more time with the patient. I can think of very few instances, except those cases where you’ve got lots of chronologic scans, where you can really predict the tempo of the disease. I find that to be quite challenging.

When I think about the response rate argument, for instance for lenvatinib/pembrolizumab, I often think about the differences in the demography in that study. More patients with good-risk disease, for instance, fewer patients who had had cytoreductive nephrectomy compared to regimens like cabozantinib/nivolumab. I tend to be a little bit more dogmatic. I tend to start most of my patients on cabozantinib/nivolumab upfront, using the general arguments of the response rate being on par with other TKI/IO regimens and reasonable tolerability. That quality of life data seems to stick out a little bit to me amongst the other TKI/IO regimens.

Dr. Rini: I think your point about limited number of kidney cancer patients is a good one. I will say, if we look at other malignancies, there’s plenty of other malignancies where there’s regimens to choose from, and oncologists may use different regimens for different circumstances. Since I don’t see those other malignancies, I can’t really cite examples, but I don’t think we should underestimate a community oncologist’s ability to differentiate among the regimens. I don’t think it has to be super complex. If they are sarcomatoid and can tolerate ipilimumab/nivolumab, then that’s a good regimen. If they’re not, or if you’re using an IO/TKI and you think they can tolerate a higher lenvatinib dose, then I think those data are more robust, notwithstanding comparisons across trials. I will agree that understanding a given regimen and being able to give it thoughtfully in terms of dosing of TKI and when to hold is important as well. Obviously, you have to be able to deliver the therapy to deliver the benefits.

Dr. Pal: I think you highlighted there 2 important circumstances, or certainly 1 where it’s a given that the patient should have some consideration of nivolumab/ipilimumab, and that’s in the patient with sarcomatoid disease, especially those dominant sarcomatoid tumors. I think those are ones where nivolumab/ipilimumab is a must. I can also think of patients who, for instance, really need to head to the OR right away for cytoreductive nephrectomy. At my institution, sometimes you’re waiting 4 to 6 weeks to get that surgery done. Nivolumab/ipilimumab is a great place to start just so you know that patient is on a systemic regimen and can get bridged through surgery without having the complications around TKIs. Sometimes I’ll vote in favor of that.

But other than that, I think that our good friend Tom [Powles, MD] always makes this point that there’s more similarities than differences amongst many of these regimens that we have for advanced renal cell carcinoma. I think that it’s just a difference in philosophy rather than looking at the individual patient in front of you and thinking, how does this large data set apply? I think that it’s that juxtaposition of the large data sets against one another that I’m probably leaning on a little bit more.

Dr. Rini: I think that’s fair, so good summary of the frontline nuances and differences in approach.

To hear more from Drs. Rini and Pal on frontline RCC treatment options, watch their roundtable discussions.

Watch part 2 of this debate.