Review of the Data of Frontline Treatment for Non-Clear Cell Kidney Cancer

A roundtable discussion, moderated by Monty Pal, MD, of the City of Hope, focused on updates in renal cell carcinoma (RCC), including treatment in both the frontline and adjuvant settings. Dr. Pal was joined by a panel that included Daniel George, MD; Brad McGregor, MD; and Cristina Suárez Rodríguez, MD.

In the next segment of the roundtable series, the panel shares how they treat frontline papillary kidney cancer.

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Dr. Pal: In the last couple minutes here, we’re actually going to chat about a topic that I know is near and dear to all of us, which is non-clear cell kidney cancer. In the interest of time, I’m going to hone in on papillary renal cell, which is probably where we have the most data. Cristina, a patient comes into your clinic and has intermediate/poor-risk disease, but the pathology, as opposed to clear cell, which is really what we focused on to date, is papillary, in this case, metastatic papillary kidney cancer. What’s your typical frontline approach there?

Dr. Suarez: In an ideal world, I would like to use a combination. I think nivolumab/cabozantinib and lenvatinib/pembrolizumab have the better data for these patients. I don’t know if we are going to use in the future the mediastinal, because we have the CALYPSO results. We have some trials ongoing that will maybe give some answers. But today, not taking into account mediastinal, I would use nivolumab/cabozantinib and lenvatinib/pembrolizumab if I could.

Dr. Pal: Makes sense. What about you, Brad?

Dr. McGregor: Papillary is such a diverse group. You have the classical papillary, then you have what used to be called type 2, which is a very heterogeneous group with a very different process. I think about them a little bit differently, to be honest. We’re fortunate we have clinical trials, and we have a trial with cabozantinib/nivolumab/ipilimumab that we actually just accrued 48 patients to. We’re hoping to get results actually quite soon, which has been a great option, and it’s ongoing with a little bit of a lower dose of cabozantinib.

I do think about it a little bit differently. For classical papillary, I agree cabozantinib/nivolumab and lenvatinib/pembrolizumab. For papillary 2, it’s exciting with the cabozantinib/atezolizumab situation. But then if you have maybe like an FH-deficient RCC, I think there’s some really nice data that maybe nivolumab/ipilimumab can do something there.

As we think about the histologies, we used to think it’s just non-clear cell, or it’s just papillary, but really histology-directed therapy is where we want to go, and some of these trials are ongoing. I think we find signals in this type or this type, and hopefully we can take that to next level and really think about how we approach this.

Dr. Pal: I’m glad you mentioned that. I’m really excited about that cabozantinib versus cabozantinib/atezolizumab. It builds on some of our prior data with cabozantinib in the frontline setting. Cristina and I are actually launching a study, which is called 304. The trial is actually going to explore sunitinib as a control arm versus XL092 plus nivolumab. I think it’ll be an interesting option for patients across 3 different histologies: unclassified, translocation, and papillary. Many folks have said, why is sunitinib the control arm? It’s because when you look at the guidelines right now, NCCN [National Comprehensive Cancer Network] and EAU [European Association of Urology], despite all our efforts to modulate them and incorporate some of these cool new options, they still read sunitinib as a preferred optional alongside cabozantinib.

Dr. Suarez: In many countries you’re not allowed to use anything else, at least in my country.

Dr. George: I think this is really the point. These are rare cancers. We need these patients on clinical trials. We’ve got to be able to lean on our larger communities to say, when you have somebody that has an unusual histology, even if they’re older, even if they don’t have great performance status or other issues, refer them in.

It’s our job to get them in quickly and get them on these studies because this is really how we’re going to advance the field and find out what are the best treatments, so we’re not stuck with treatments that are 15 or 20 years old, still treating the same way. I’m really glad you guys are doing that study, and I’m hoping as much as possible these papillary patients can find their way into clinical trials because we do consider this a rare disease.

Dr. Pal: You put it so beautifully, Dan. I do think that there’s some challenges in terms of how we manage these patients—the single-arm tyrosine kinase inhibitor (TKI)/immuno-oncology (IO) data looks great, but it’s single-arm data. We really do need the randomized studies to really confirm benefits. It sounds like we’re all on the same page there, which is terrific.

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Continue on to watch the next roundtable segment.