Panelists Discuss Their Algorithm for Treating Frontline RCC

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 first segment of the roundtable series, the panel discusses the approach to frontline treatment selection for patients with RCC, including IO/IO versus IO/TKI therapy considerations.

Watch the next segment in this roundtable series.

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Dr. Rini: We’re going to talk about kidney cancer. We’re going to incorporate some ASCO data. There’s several phase III trials that have either been updated or new data. Again, talk about the frontline and refractory space; I think there’s been a lot of exciting data and some potential practice-changing data. Tian, I’m going to call on you first. Let’s talk about, as you were heading into this year’s ASCO, tell me about your algorithm for treating patients.

Dr. Zhang: We know there’s multiple approved immunotherapy options in the frontline space. I start there. There’s ipilimumab/nivolumab for a pure immunotherapy approach. We know CTLA-4 inhibition has a great role upfront. For patients who are immunotherapy appropriate and looking for durable responses, I’m starting there. For early disease control and early responses, I turn toward the VEGF/IO combination. We have multiple now approved: axitinib with pembrolizumab, axitinib with avelumab, which is not often used, also lenvatinib with pembrolizumab, and then finally cabozantinib with nivolumab. As we go down those treatment algorithms, and I’m sure we’ll talk through all of those data, I’m often thinking about patient characteristics and then how quickly they need a response.

Dr. Rini: Are you, just to clarify, sort of ipilimumab/nivolumab as a default, assuming they can tolerate ipilimumab, etc.? Then if they have bulky symptomatic disease, you might lean toward an IO/TKI. Is that a fair summary?

Dr. Zhang: That’s a fair assessment, yeah.

Dr. Rini: When you give IO/TKI, what do you give?

Dr. Zhang: I actually use all of them. If I’m thinking I want to save cabozantinib for the second line or later, I’ll start with axitinib with pembrolizumab or lenvatinib with pembrolizumab. If I’m looking for really good early disease control, I might lean a little bit more toward cabozantinib/nivolumab or toward lenvatinib with pembrolizumab.

Dr. Rini: Higher response rates with lenvatinib/pembrolizumab, but more toxicity, which we’ll talk about. Okay, Pedro?

Dr. Barata: Great summary, Tian, it was perfect. As you’re walking through your way of approaching those patients, I would probably highlight, I’m assuming your answerer is referring to clear cell? For non-clear cell, we also have data supporting IO/TKI in that setting with lenvatinib/pembrolizumab and cabozantinib/nivolumab. For that reason, I do care about that. I do offer IO/TKI in general to patients with non-clear cell. Then other factors, we do start having data about specific subgroups, patients with bone metastasis, patients with liver metastasis, maybe CNS [central nervous system] disease, although we also address them locally first. For those patients I tend to use a bit more IO/TKI. Then my final point was obviously one of the things we care about is sarcomatoid rhabdoid features as well. I definitely take into consideration that and also trying to favor definitely IO if not IO/IO. Meaning I do a lot of ipilimumab/nivolumab in those patients as well.

Dr. Rini: Ipilimumab/nivolumab for sarcomatoid, right? There’s some good albeit subset retrospective data. Then were you saying that you choose based on site of metastasis?

Dr. Barata: Well, no. Because all the patients are different, I think presentation of location of metastasis matter in the way I think about it. Not necessarily symptomatic patients or visual crisis, but I do think of a patient who has a number of liver metastasis in addition to lung, lymph node, very different way that I look at a patient with a pancreatic metastasis or a few lung metastasis. If I have this urgency and I really care about how likely is the treatment, whatever I do, not to work and what data do I have to do in those cases; if I really concerned about this might be my only chance, we tend to think that liver metastasis and bone metastasis almost behave differently, I tend to go in IO/TKI that provides for that. In general, I tend to think of cabozantinib/nivolumab and lenvatinib/pembrolizumab in those cases.

Dr. Rini: What you’re referring to is that PD as best response, which is about 5% or 10% with the IO/TKIs and more toward 20% with ipilimumab/nivolumab.

Dr. Barata: Correct.

Dr. Rini: That may have consequences. Not in all patients of course. Small volume disease, not, but okay. Mike?

Dr. Atkins: Yeah, I’m not dissimilar from what both of you have presented, although maybe a little bit more biased toward giving IO/IO to most patients. Because I think most of my patients want a durable response and want to be able to stop treatment and get back to their prior lives. Pure IO regimens are the only ones so far that we can see that can actually do that. I think the data presented at ASCO suggests that that may still be the case. I take patients who have really aggressive disease and where we absolutely need a response, patients who are really symptomatic or in the hospital and if they have heavy bone metastases, I might give them cabozantinib/nivolumab. If they have bad lung disease or something like that, I might give them lenvatinib/pembrolizumab. But for the most part, I view TKIs, which are great drugs, but as drugs that are not curative. I try to delay starting those as long as possible in my patients.

Dr. Rini: Two questions for you. What percent of patients in your practice will get an IO/TKI based on those parameters?

Dr. Atkins: Probably 5% to 10%.

Dr. Rini: So a fairly low percent. Then what percent of patients walk into your clinic and you think, “This patient is just not going to tolerate ipilimumab. This is going to be too much for this patient.” Put aside rheumatoid arthritis or autoimmune or organ transplant or something like that, but just sort of their performance status and fitness level makes you worry?

Dr. Atkins: I think if they can’t tolerate ipilimumab because they’re old or you’re worried about their performance status, I think it’s going to be hard for them to tolerate IO/TKIs as well. I would rather either do an IO or ipilimumab/nivolumab with a very short leash or give single-agent anti-PD-1, which we know has activity. If you have a patient who let’s say has an autoimmune condition, history of colitis or history of arthritis where I’d be worried about giving them ipilimumab, I think it’s fine to give them single-agent anti-PD-1. I’d rather do that than an IO/TKI in that setting.

Dr. Rini: Okay, interesting. I’m probably a little bit different. I tend to be an IO/TKI guy. I give ipilimumab/nivolumab to younger healthier patients obviously that I think can tolerate ipilimumab and sarcomatoid for sure. I think any degree of sarcomatoid would buy them ipilimumab/nivolumab.