Balancing Risks and Rewards in RCC: IO Combinations for Different Patient Profiles

In the first part of this roundtable series, Dr. Michael Atkins, of Georgetown Lombardi Comprehensive Cancer Center, and an expert panel of oncologists discuss and debate the latest strategies for optimizing first-line treatment for advanced kidney cancer. This discussion explores the nuances of choosing immuno-oncology regimens, considering patient characteristics like ECOG performance status and IMDC risk stratification. Key topics include treatment approaches like nivolumab-ipilimumab and IO-TKI combinations, strategies for managing patients in both academic and community settings, and tailoring treatment for favorable- and poor-risk patients.

Watch the second segment of this series: Biomarkers in RCC Treatment: The Role of Sarcomatoid Features and Emerging Technologies

_

Dr. Atkins:
Good day, I’m Dr. Atkins, deputy director of the Georgetown Lombardi Comprehensive Cancer Center in Washington, D.C. And I’m the moderator for a session on optimizing first-line treatment for advanced kidney cancer. I’m here with Dr. Park from the Norton Cancer Institute in Louisville, Kentucky. Dr. Lattanzi from Texas Oncology in Boston. Dr. Tan from Vanderbilt, here in Nashville and Dr. Albiges from Institute Gustave Roussy in Paris. So welcome and we’re going to have a lively discussion on where things stand in first-line treatment of patients with advanced kidney cancer. So for our first question I want to ask, and I’m going to start with you, Laurence, how do you tailor your choice of IO regimens based on individual characteristics such as ECOG, performance status, disease stage, or IMDC risk stratification in patients with metastatic clear cell kidney cancer? 

Dr. Albiges:
Thank you very much. Thank you for having us. So I think to keep it simple, first thing is to stress is, is it a clear cell RCC or non-clear cell? And so if we dig in for clear cell RCC, my next step, because of the approval, is to check on the IMDC risk group. Not only approval, but also to assess the prognosis of my patient. And if we fall into the largest body, which is IMDC intermediate and poor, meaning the patients have had least one poor risk feature, then the question is, should I go for an IO/IO strategy or an IO/TKI? So namely nivolumab ipilimumab or one among nivolumab cabozantinib, lenvatinib pembrolizumab or axetinib pembolizumab. 

And the way I see things is the following, does my patient has highly symptomatic disease or lesion that I consider at risk, for which I don’t want to have a risk of upfront disease progression? And in this situation, I will pick one of the IO/TKI regimen I have listed. But for the vast majority, if my patient doesn’t have lesion at risk, what I want is the long-term benefit. And here we have the longest body of data with nivolumab ipilimumab eight year follow-up that clearly support the fact that this approach is able to achieve durable response, even complete response in about 12% of the patients. We do have patients that are not responding to this strategy, but I want to give it a try so that I can achieve long-term disease control. 

Dr. Atkins:
Thank you. So Alan, are you bound? I think in France, the IMDC category restricts what you can do. Are you bound by the IMDC category and is your approach the same? 

Dr. Tan:
So the FDA indication is for intermediate and poor risk. But now that we have eight-year follow-up from CheckMate 214, we now see that the hazard ratio for overall survival, the good risk actually in my opinion looks the best out of all of them. And these patients are actually off treatment, a lot of them. So you get durable remissions and patients that are treatment-free. So in the NCCN guidelines, which is what we usually use in the United States, there are three IO/TKI regimens that are listed currently as category one. And they just recently added Ipi-Nivo as another option. Unfortunately, it still doesn’t say category one yet. I’m not sure what other evidence they need. But I’m starting to… Well actually to be honest, I had been using them in good risk because I know that even in the earlier follow-ups, there was a complete response rate of 10% at least. And so I think those responses have been durable. 

Dr. Atkins:
So Mike, how did you in the community approach this first-line treatment choice? 

Dr. Lattanzi:
Sure. So I work for a large community-based practice. We’re spread across close to 200 offices throughout the state of Texas, including both urban city practices as well as practices in small towns in Texas that you’ve probably never heard of. And there’s all kinds of challenges to practicing in those settings. Obviously, the resources vary quite a bit. The patients vary quite a bit than what I think is typically encountered in an academic or hospital-affiliated practice. Frankly, I don’t tend to see very many good-risk patients. The majority of my patients are intermediate and poor-risk. And frankly, part of my job as a community-based provider is rounding daily at the hospital. Many of my advanced RCC patients actually present to the hospital for pain crisis, gross hematuria, et cetera. And so they’re presenting in most of them with relatively advanced and aggressive disease. These are not the patients who would typically make it to a large tertiary care center. So for the most part, I try for the reasons that we’ve talked about to expose patients to Ipi-Nivo if I think that they can afford a degree of disease progression and make it onto second-line therapy where we could potentially salvage the response. But for a lot of our patients, I also encourage them to pursue an IO/TKI combination, mindful that they may not make it onto a second-line of therapy. 

Dr. Atkins:
And if you did see patients who were favorable-risk or intermediate-risk and would be the type of patients who could go on a protocol or the ones on the protocols, what choice would you make in that setting? 

Dr. Lattanzi:
So in that context, I think the data is very clear that CTLA-IV blockade is required for long-term durability or remission. And I think it’s worthwhile of consideration even in those good-risk patients. So for any patient that should be part of the conversation in terms of selecting treatments. And so because of the durability of CTLA-IV blockade, I do tend to recommend a lot of ipilimumab and nivolumab in the front-line setting irrespective of IMDC risk group. 

Dr. Atkins:
Okay. Chandler? 

Dr. Park:
Yeah, I agree with a lot of the same points. I practice in Louisville Kentucky, which is the sixteenth-largest city in the United States. But I get a lot of second opinions from community areas outside of Louisville, these rural hospitals and so they’re on islands. And so what I talk to them about is, is this person… Do they have symptoms? Are they symptomatic? If they’re symptomatic bulky disease, I do consider immune checkpoint inhibitor and TKI. Primarily because of the primary progressive disease based on the clear study, 5% CheckMate 9, ER 7%. But then how many of the patients are truly symptomatic? So I start thinking to myself, if they can pass that two-year window, you got the 99 month follow-up, these patients have that durable response. And so with that updated Dr. Nazir presented at ASCO GU this year, it’s changed my view on things, to give that patient an opportunity to have that long-term durable response with detail.