Panelists Share What Is Most Exciting in Frontline Kidney Cancer

A roundtable discussion, moderated by Brian Rini, MD, of the Vanderbilt-Ingram Cancer Center, focused on treatment considerations for frontline and refractory renal cell carcinoma, including a discussion of new data presented at ASCO 2023. Dr. Rini was joined by a panel that included Tian Zhang, MD; Pedro Barata, MD; and Michael Atkins, MD.

In the next segment of the roundtable series, the panel discusses what is most exciting to them in the frontline RCC field, including a review of the OPTIC and PDIGREE trials.

Watch the next segment in this roundtable series.

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Dr. Rini: What are you most excited about in frontline kidney cancer? Where do you think the field should go? What are you most excited about? Mike, we’ll start with you.

Dr. Atkins: There’s another poster that was presented at ASCO from Sabina Signoretti, MD, that looks at some biomarkers in the Hoosier trial that looks at both the CD8 T cells and whether they’re only partially exhausted and have PD-1 on their surface or have LAG-3 or TIM-3 on their surface. Which makes them completely exhausted and also potentially looks at PD-1 on Tregs, which may actually, when exposed to therapy, might make the Tregs more suppressive.

I think looking at those types of things as potential biomarkers, one for response and one for resistance and then putting them together, I think we have to realize there’s a balance going on in the tumor microenvironment. Some things favoring a response, some things inhibiting a response. I think we need to look at and understand that, and potentially figure out adding things to anti-PD-1 and maybe anti-PD-1, anti-CTLA-4 that can eliminate some of those immunosuppressive factors in the tumor microenvironment while we’re activating T cells. I’m looking at CTLA-4 antibodies that might be Treg depleting, looking at potentially blocking other checkpoints as we’ve talked about and as we’ve done in melanoma such as blocking LAG-3 as ways of moving things forward.

Dr. Rini: Other immune manipulations basically in the frontline setting. Pedro?

Dr. Barata: Thank you Tian, for bringing it up. Your trial OPTIC is one of the exciting things. We’re happy to have it in Cleveland as well. For those less familiar, you’re basically doing a molecular signature upfront and you are assigning an immunotherapy (IO)-based approach: IO/IO or IO/tyrosine kinase inhibitor (TKI) based on that signature front. It’s so important for a lot of reasons; number one, scientifically perhaps it will be used in the future if pans out or at least will need to be confirmed. But also it brings genomics to the kidney cancer world, the same way we’re doing in other tumors because it will help us to all figure out how we can use genomics with time that is actually feasible because we cannot be sitting waiting 3 months for genetic or signature score, for instance, for us to decide what to do.

From that perspective, that trial puts the right pressure in the different institutions to get the field to actually start adopting molecular profiling as part of the information that we need upfront, in addition to clinical characteristics, lab characteristics, for us to better select patients. That’s one. The other one is the microbiome. We’ve seen emerging data that impacted the gut microbiome. It does have implications in the activity or seems to have implications in the activity of immune therapies, including immune checkpoint inhibitors. You have data in lung, in kidney cancer, and actually we just saw 1 proof of concept, a study first with ipilimumab/nivolumab from Monty Pal, MD, and the City of Hope group and with ipilimumab/nivolumab and probiotic CBM 588, which is Clostridium butyricum if you will. Now we kind of see the same thing at ASCO, similar results in the same line within IO/TKI.

The results are very provocative; they need further confirmation. But I do believe we’re getting this new era of learning how we can actually assess the gut microbiome. It’s not easy. How do we actually deal with stool samples in addition to blood samples and urine samples, etc., and tissue samples. We’re actually learning a lot about it. I do believe the field is moving as a whole. It’s moving and maybe if we figured it out the way to optimize the activity of immune manipulations, I think that the potential is huge that can go beyond kidney cancer.

Dr. Rini: Biomarkers and also immune manipulation, in this case microbiome. Tian, what are you excited about?

Dr. Zhang: I can’t let a first-line discussion go without talking about PDIGREE. Full disclosure, I’m biased as a study chair, but PDIGREE is a sequencing trial of sorts. So ipilimumab/nivolumab upfront and then randomized to nivolumab or nivolumab/cabozantinib, really building on CheckMate-214. We have been enrolling for 4 years in the cooperative groups and we are nearing the finish line, but not quite there yet. But I think once PDIGREE reads out, we’ll have more sequencing data. We’ll have more treatment discontinuation data as well about complete responders at 1 year. How do they do? The deep partial responders who go on to get consolidated surgery or radiation. But I think it answers a lot of questions about sequencing and how patients do over time and to the point that patients are living longer, they’re getting subsequent therapies. I think thinking about sequencing optimally is important for these folks.

Dr. Rini: Yeah, and I think PDIGREE is a good example where you put the trial out there and you do it and people say, “Oh, it’s a great trial. It’s a terrible trial, it’s a great trial.” I’m sure you’ve experienced this. But at the end of the day, it’s going to answer a lot of questions. I agree with you.