CheckMate 214: Long-Term Survival Implications, Treatment Ramifications for Favorable-Risk Patients

Saby George, MD, FACP, Roswell Park Comprehensive Cancer Center, continues with a discussion on the survival implications as well as treatment ramifications resulting from the CheckMate 214 long-term data presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium 2024.

View Dr. George’s previous comments on the CheckMate 67T study.

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What are your overall thoughts on the CheckMate 214 8-year survival data? Is there any new information to be gained, or is it confirmatory of what we already knew?

Dr. George: Overall, it confirms the long-term benefits of this regimen, which I have been involved with since the trial’s inception. It is noteworthy that this is the first time such extensive long-term data has been reported for frontline combination treatment in kidney cancer. At the 8.5-year follow-up, we have discovered a couple of important insights.

As you know, ipilimumab and nivolumab, approved in 2018 based on CheckMate 214, are primarily used for intermediate and poor-risk patients with kidney cancer. The favorable-risk group, as defined by IMDC, is not typically included because the trial was enriched for intermediate and poor-risk patients. Additionally, short-term data favored sunitinib in terms of progression-free survival. However, the long-term results reveal that overall survival actually favors ipilimumab and nivolumab, as presented by the CheckMate 214 team.

So, while sunitinib showed better progression-free survival initially, ipilimumab and nivolumab demonstrate superior overall survival in the long run. This may prompt consideration of ipilimumab and nivolumab for the favorable-risk group, pending guideline adjustments or FDA approval. It underscores the value of this regimen.

In any trial, short-term endpoints like response rate or progression-free survival are common, but overall survival remains the gold standard. It is often seen in immunotherapy trials that short-term endpoints may not align with long-term outcomes. This discrepancy, as demonstrated here, highlights the importance of prioritizing overall survival, which patients typically value more.

How does nivolumab/ipilimumab compare to other frontline options for patients with favorable-risk disease?

Dr. George: I have been involved with all the trials leading to approval. Considering one factor, the durability of response, even though the response rate is lower with nivo/ipi than with other options, the durability of response is superior with nivo/ipi based on the available data. The PFS and OS curves plateau in this trial, indicating prolonged benefit.

Another reason for this prolonged durability is the treatment-free interval. A couple of years ago, we published data from this trial mentioning the treatment-free interval. Patients who experienced toxicity and discontinued treatment due to immune-mediated adverse events often did not require a second treatment because of the durability of their response and lack of progression. This further highlights the long-lasting benefit of this regimen, suggesting potential reconsideration of treatment recommendations based on this extensive long-term data.