RCC Panel Reacts to Long-Term Follow-Up From CheckMate 214

A roundtable discussion, moderated by Brad McGregor, MD, focused on the latest data in RCC treatment and management, including data from the American Society of Clinical Oncology Genitourinary Cancers Symposium 2024. Dr. McGregor was joined by Rana McKay, MD; Elizabeth Wulff-Burchfield, MD; and Alan Tan, MD.

In the next segment of the roundtable series, the panel shared their thoughts on the 8-year follow-up data from CheckMate 214.

Watch the next segment in this series.

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Dr. McGregor: I thought we had some really interesting data on CheckMate 214 today, so I don’t know if you want to go through what they showed.

Dr. Tan: Right, so now we have an 8-year follow-up, for CheckMate 214. There’s 1 mg/kg of ipilimumab plus the standard dose of nivolumab compared to sunitinib. We now have the hazard ratio for survival is maintaining around the same, about 0.65 range. The interesting thing that I noticed is that even though ipilimumab/nivolumab is approved only for intermediate and poor risk, and we thought that sunitinib outperformed these patients in the good-risk population, actually with longer follow-up, it’s actually starting to look pretty good, and the hazard ratio for survival with ipilimumab/nivolumab in good risk is actually 0.849, I believe, right? I think it’s a conversation that should be had. Dena Battles’ survey where patients number one desire is to be cured, to have a chance of cure, to have a chance to actually stop therapy. When patients are actually on IO/TKI therapy, it’s pretty uncommon for these patients to be off therapy and disease free for an extended period of time.

We know from KEYNOTE-426 and CheckMate 9ER and maybe CLEAR as well, that there’s no tail of the curve, at least not yet. Maybe CheckMate 9ER, we still have to look longer, but the curves are starting to come together with KEYNOTE-426, which is the longest IO/TKI combination. As someone that also treats melanoma, we desire that tail of the curve, and I think we need to build upon that and raise that tail of the curve and build upon the IO/IO backbone.

Dr. McKay: Yeah, absolutely. The number 2 most impactful kidney cancer presentation was CheckMate 214 because I think this is huge for our patients because I think these are favorable-risk patients. A lot of times they’re asymptomatic, they feel good, they have low burden of disease. I think the general mantra has been IO/TKI for these patients.

We know the impact of chronic TKI exposure on quality of life. These patients are going to be the patients that are going to be able to get a second shot at getting treated, receive multiple subsequent lines of therapy. I think this is really important. I think it’s important for guideline implications for NCCN, SITC. We’ll see how the European guidelines interpret this data. I also think it’s going to be really impactful as we design future trials in the field. Thinking about nivolumab/ipilimumab as a potential control arm for an all-comer study, including favorable-risk patients. I think these data are going to be really impactful in, in multiple ways. I think we need to get this message out in front of our local community oncologists that see these patients, share this data, and think about how the guidelines can reflect the new data.

Dr. Wulff-Burchfield: I would argue that not only, could it be presented to favorable-risk patients as an appropriate treatment option? I would argue that it probably should be now that we’re seeing this.

Dr. McKay: Completely agree.

Dr. Wulff-Burchfield: For many of these patients, this is their one opportunity to potentially seek treatment-free survival and ultimately that’s what patients want if we can provide it and thankfully their lower disease burden and lower symptom burden does protect them such that we are almost guaranteed to be able to offer them subsequent therapy. It feels like there is a change in the tone of this recommendation. I realize on guidelines is kind of a little asterisk, but like you, I’m really hoping that this changes to a little bit more definitive spot in the guidelines.

Dr. Tan: What do you guys think? Are we moving away from the IMDC?

Dr. McKay: We should be moving away from that. IMDC was not designed as a predictive marker for therapy selection. It’s prognostic. It continues to remain prognostic in the modern era of people receiving IO therapy, but it should not necessarily guide how we select patients for treatment, and I think the only reason that it is being used that way is largely because of the way CheckMate 214 was designed. The primary end point of CheckMate 214 was focused on the intermediate and poor risk. There’s been this linkage of IO/IO to that population, but I’m hoping that we can move away from that. I almost would challenge the guideline panels to not necessarily break things out by or favorable, intermediate, and poor risk because those are not predictive markers of response to treatment.

Dr. Wulff-Burchfield: It’s tough  because I feel like that’s sort of the opposite of what the messaging has been for our colleagues in the community this time. Please consider using this so that we can have a different breadth of options to offer. Now we’re sort of needing to de-implement that. That’s kind of a profound thing.

Dr. McKay: Hopefully simplify.

Dr. Wulff-Burchfield: Exactly. I think it will be really advantageous to all parties. I agree. I think that is important messaging.

Dr. McGregor: I agree. I’ve thought that based on like the 6-year follow up when we had that. I was intrigued. I am personally really excited by that tail. It’s a pretty high bar. You look at that mean duration response over 80 months. Start doing math, how many years that is, that’s over 5, it’s like crazy.

Dr. McKay: Those are deep, durable responses.

Dr. McGregor: And 40% of patients respond, so you can tell the patient, if you respond, that could go on for years. You may be cured. When I first started treating kidney cancer, when it spread out to the kidney, I’m like, listen, I can treat this, but it’s very difficult to cure. We were wrong, right? You may be curing patients.

Dr. Tan: It sounds like we’re all big fans of the data, but we also should not oversell the fact that it’s not for everyone. It does have a primary progressive disease rate of about 20%. Really making sure the audience knows that patients that are highly symptomatic, poor performance status, we don’t want to lose these patients and they don’t go on to second-line therapy too. Those patients are probably better candidates for IO/TKI.

Dr. Wulff-Burchfield: Very important. Protect them, keep them safe, make sure we can debulk their disease enough just for them to maintain or rebuild their health so they can continue on treatment.

Dr. McGregor: Yeah, 20% PD as best response. If you respond to ipilimumab, it’s great. But the chance of no response is the highest with this regimen. You want to make sure.

Dr. Tan: We know IO takes time to engage. Sometimes patients don’t have that luxury of time to engage.