What Matters Most: Shared Decision-Making and Treatment Endpoints in RCC

In the third segment of this panel discussion, Dr. Michael Atkins leads a conversation on the key treatment endpoints that matter most for both doctors and patients when deciding between IO-IO and IO-TKI therapies for advanced kidney cancer. The discussion, featuring Dr. Chandler Park, Dr. Mike Lattanzi, Dr. Alan Tan, and Dr. Laurence Albiges, explores the balance between managing side effects, achieving durable remission, and addressing patient priorities such as overall survival and treatment-free outcomes. They dive into topics like the role of biomarkers, intermittent therapy strategies, and the challenges of treatment in different healthcare systems.

Watch part four of this series: Subcutaneous vs IV Nivolumab: A New Frontier in RCC Treatment Delivery

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Dr. Atkins:
So switching over from this selection of first-line therapy, I want to talk a little bit about what endpoints do you most care about and do your patients most care about as you’re thinking about giving treatment? And we’ll start with you, Chandler again. 

Dr. Park:
Yeah, our patients… We live in a society where we do a lot of walking and talking with the patients and we have combined shared decision-making and so I think this is a very critical piece where we talk to the patients. And when we talk about broadly the IO/IO strategy versus the IO/TKI, I think to myself about the side effects of IO/IO. Maybe a little bit more upfront toxicity, but then once they pass three or four cycles, you start watching the hypothyroidism, look for adrenal insufficiency. But then once they get to the monotherapy of nivo it is cruise control to me, it seems like the patients are doing really well. But on the other hand, with the IO/TKI, it just builds over time, whether it be hypertension, whether it be diarrhea, the LFTs. And so I start talking to the patient and say, “Okay, these are the side effects of IO/IO. We might have to get an endocrinologist on board. These are the side effects of the IO/TKI. We might have to take treatment holidays, we’re going to have to check the blood pressure, we have to monitor the diarrhea.” And then we sit down and talk and say, “Okay, which of these means the most to you?” So for me as an oncologist, overall survival means a lot, is the gold standard, response rate means a lot, and also primary progressive disease. So those are the main things that I look at. 

Dr. Lattanzi:
Yeah, I mean my typical patient, even the ones who know that they’re metastatic deep down they want cure, they want the cancer gone, they want a shot at durability. And in those cases where I think it’s feasible, I think it’s most reasonable to offer them a chance that durability with ipilimumab. Sometimes we don’t have a choice, like you mentioned, patient who’s highly symptomatic on oxygen, pleural effusions, in a wheelchair, where we really just need to start TKI therapy. Certainly in the hospital sometimes we’ll just start TKI therapy because we have easy access to the TKIs urgently. But for patients who can afford to wait for a response, the patients really want that chance of durability. 

Dr. Atkins:
And Alan, what’s your experience in stopping IO/TKI therapy versus stopping IO/IO? 

Dr. Tan:
Yeah. To be honest, IO/TKI… I think you said it best when you walked into your amigos last year, patients feel like they’re on TKI jail. I think one of your patients described it that way. So essentially if you’re an IOTK regimen, it’s very rare for them to actually come off and be disease-free indefinitely. I agree with Chandler that there is a chance based on the STAR trial and the TIDA trial that we can do intermittent breaks even up to 90 days. We’re trying to develop a trial of Vanderbilt II to look at an intermittent approach using radiographic and also CT DNA clearance to do that. But opposed to IO/IO, we have eight year follow-up. And if a patient wants to know what’s my best chance of living the longest and actually being treatment-free, Ipi-Nivo has now shown that about a third of patients can have a durable remission with that combination. 

And let me just say one more thing. There was a KC Cure survey that I think David Braun presented at one of the major conferences led by Dena Battles. And it was a survey to many patients throughout the country, “What’s your number one goal in your cure in frontline systemic therapy?” And it’s the chance to have a cure and to actually be off treatment. They’re willing to take more risk as far as toxicity. So CTLA-4 of course has more IRAEs, although not as much as we have in melanoma, but because it’s a lower dose ipi. But you may have some of those higher risk endocrinopathies, neuropathies, et cetera. But if that’s for a long-term growth of actually being off therapy and maybe even zero-state cure. I’m not sure if all of us agree that these patients eight years out that are off treatment are cured, I certainly think so. 

Dr. Atkins:
So Laurence, you’re restricted in France to give… You can’t give IO/IO to favorable risk patients, but how do you justify giving IO/TKIs when the hazard ratio is flat one for all of the IO/TKI overall survival and it’s hard to stop therapy? 

Dr. Albiges:
Thank you for the hard question. So my check is the following. It’s basically hitting hard. So I do explain to the patient that we are providing a dual approach with two mechanism of action that actually covers both the biology that you were describing, the angiogenic-driven biology, but also the potential T-cell infiltrate biology. And that what I’m looking for is basically in-use as much tumor shrinkage as possible, which will be a load by the combination therapy with the latitude of reducing the TKI because of daily toxicity we discussed and perform drug holiday. And this is clearly a situation where I am offering drug holiday. From a patient perspective, the drug holiday they are keen on having is the one with the TKI. 

But one could also say, “Oh, there is a potential to discontinue the immune checkpoint inhibitor.” We have academic trials trying to ask this question in great responders, can we stop at one year or can we dose reduce or spread a bit more the infusion of the immune checkpoint? So this is investigational of course. But my point is that we know the combination provide longer progression for survival, meaning the time to the need of the change of systemic treatment. There is a likelihood of achieving complete response. And that is important for the patient, although in good risk, usually they’re not highly symptomatic and they have a small metastatic burden. But I think ultimately that will help to… Although for some de-escalation. So that’s the reason why I’m sticking to combination therapy in IMDC good risk.