IO-IO Regimens in Advanced RCC: Recent Data Updates


Expert oncologists review data updates on IO-IO regimens in the treatment of advanced RCC, including CheckMate 214, and discuss treatment selection among IO-IO and IO-TKI combinations.


Elizabeth Wulff-Burchfield, MD: In this case, our patient received nivolumab-ipilimumab because she saw 1 of you brilliant doctors here. In thinking about that, and getting us back to the CheckMate 214 data, it’s unbelievable to see how long of follow-up we have with the CheckMate 214 data. As a reminder, these patients had to have a clear cell component to their disease and received sunitinib or nivolumab-ipilimumab. One thing that’s interesting is that it’s my understanding that the patients who went on to nivolumab maintenance were those who received all 4 doses of nivolumab-ipilimumab on this trial, which is a little different. This is the parent trial for COSMIC-313. The primary outcomes were co-primary end points focusing on the intermediate- and poor-risk population looking at overall response rate and PFS [progression-free survival]. Certainly, all the other relevant end points were captured. These aren’t the primary outcome data. This is looking at overall survival.

We see that in the intent-to-treat population, which included all risk stratifications. The intermediate- and poor-risk subgroup was the population on which that primary end point was based, and we do see clear improvement. The hazard ratio is hovering around 0.7 for patients who received nivolumab-ipilimumab compared with sunitinib. In the favorable-risk subgroup, things were similar. This was from 2021, and as we see maturation of these data, we see that hazard ratio creeping down a little. There’s clearly a numerical difference in overall survival. Like all of you, I agree that nivolumab-ipilimumab is an important part of the discussion for patients across the spectrum of risk categorization.

Regarding safety, this safety profile looks really different. When you look at the TKI [tyrosine kinase inhibitor]–IO [immuno-oncology] combinations compared with sunitinib, we see these tornado plots that are pretty much symmetrical. It looks different because the nature of this mechanism is so different from a VEGF TKI. As we’ve all learned and experienced with these, the profile looks different and patients are often carrying this toxicity for shorter periods of time. Fatigue can go on [longer], but when it comes to diarrhea, rash, and nausea, we often see shorter durations of those because the way we intervene is so different compared with chronic toxicity for [patients] who are living with active cancer on active daily therapies. And we see a healthy proportion of patients who needed a dose interruption as expected.

But let’s get back to all your insights. We’ve covered this well, so I want to reserve plenty of time for future discussion points. Are there any further insights about patients for whom you’d prioritize nivolumab-ipilimumab? Dr Barata, you were talking earlier about patients with sarcomatoid [carcinoma] and rhabdoid [tumor]. It sounds as if that’s a group for whom you might prioritize nivolumab-ipilimumab as opposed to a TKI-IO regimen. Is there anything that hasn’t been touched on or that you want to expand on?

Pedro Barata, MD: Yes, although for sarcomatoid or rhabdoid, we don’t have head-to-head [data] saying nivolumab-ipilimumab is better, but a predictive marker can tell you with high level of competence that immunotherapy makes sense and is going to work. Naturally, you want to offer immunotherapy and save the TKI for later. A lot of us do that. But the IO-TKI cocktails have shown similar benefit in regard to higher activity and clinical outcomes for patients with sarcomatoid features.

Regarding this point, I want to highlight something that was mentioned earlier. My practice has changed. I was thinking about nivolumab-ipilimumab in some cases in the salvage setting where they haven’t seen a CTLA4 inhibitor in the front line. For the last 2 to 3 years, we did a number of studies going the same direction with more limited activity of an ipilimumab-based approach in the salvage and the recurrent space. I’ve been doing that in very select cases. That’s 1 message. If you want to do a CTLA4 inhibitor—in this case, ipilimumab—I tend to do it in the front line and not later.

For intermediate- and poor-risk [patients], we talked about the analogy of playing the short game or the long game. Do you have time? Another way of saying that is if nothing is going to happen, if the patient doesn’t benefit from therapy and you can salvage him with another treatment, nivolumab-ipilimumab is a good thought. If that doesn’t work, that patient will be in trouble and you might not be able to salvage and get control of the disease. You’re probably going to use an approach that will give you the maximum activity. That’s the short way of answering that question about response rate. You’ll see the tumor get smaller, and that’s what you want to see. At a minimum, we don’t want to see progression. That probably favors IO-TKI.

It’s also nuance. Some of us will look more at location of metastases plus symptoms; others, more symptoms than tumor burden. We all define things a little differently. Those are my thoughts in addition to everything that was said. The conversation around nivolumab-ipilimumab was stronger in the intermediate- and poor-risk [population] because of the way CheckMate 214 was designed compared with the good-risk [population]. Before we had IO-TKI combos, some of us were doing it even in good-risk [patients], but there wasn’t an intent-to-treat population. Therefore, nivolumab-ipilimumab is a level 1 recommendation in this group of patients.

Elizabeth Wulff-Burchfield, MD: Thank you so much. I appreciate that.

Transcript edited for clarity.

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