CheckMate 9ER: What Is the Impact for RCC?

A roundtable discussion, moderated by Rana McKay, MD, discussed the latest updates in frontline treatment for renal cell carcinoma, including how data from the American Society of Clinical Oncology Genitourinary Cancers Symposium 2024 alters the treatment paradigm. Dr. McKay was joined by Nizar Tannir, MD; Hans Hammers, MD; and Katy Beckermann, MD.

In the fifth segment of the roundtable series, the panel highlighted the CheckMate 9ER study and implications for clinical practice.

Watch the next segment in this series.

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Dr. McKay: There has been a lot of talk on CheckMate 214, presenting really exciting data. We also received updates from CheckMate 9ER, which investigated nivolumab and cabozantinib. Once again, we continue to observe a benefit over time. The survival curves remain separated, though not increasing, maintaining about a 10 percent delta between them. Any thoughts on CheckMate 9ER?

Dr. Beckermann: I must say I was impressed by the positive aspects, particularly the CR rates. It is always heartening to see a focus on potential cures. I recall a 16% CR rate, perhaps even a bit higher overall. So, it is encouraging to see some patients achieving a complete response. As you mentioned, the combination of immunotherapy and TKIs continues to demonstrate promising initial responses, as observed in CLEAR and KEYNOTE-426. However, there might be some concerns about the tail of the survival curve potentially flattening out.

Dr. Hammers: It is like a race to the bottom. I find it fascinating. It is not often we see such a prolonged tail. Kudos to the companies presenting this data. Pfizer showcased the axi/pembro data at the last ASCO, and it seems they all share a similar trajectory, albeit with varying plateaus. Nevertheless, none seem to match the extent of durability demonstrated in CheckMate 214. Hence, in my opinion, the combination of dual checkpoints seems to be the most promising approach for achieving long-term outcomes.

We have an ongoing trial within the kidney cancer consortium exploring triple therapy, leveraging this dual checkpoint backbone. If we can indeed induce durable responses exceeding 50%, it could significantly impact the duration of response, potentially even altering progression-free survival outcomes. So, there seems to be a clear regulatory pathway here.

Dr. Tannir: Regarding the duration of response, Dr. Hammers, it stands at 82.8 months.

Dr. Hammers: How does that compare to the usual PD-1/TKI regimen, typically around 20 months?

Dr. Tannir: It is 26 months, but with a shorter follow-up. The proponents of IO/TKI may argue for a longer follow-up period, but I doubt it would substantially alter the data. Currently, IO/TKI shows a median duration of response of around 2 years. In contrast, here we are seeing a quadruple increase in duration compared to sunitinib, almost double that of nivo/ipi even in favorable risk patients.

Dr. McKay: I appreciate the point you raised about the equivalence in duration of response between IO/TKI in favorable-risk patients and TKI alone. Considering TKIs do not lead to cures, this is indeed promising. It is reassuring to have such options available.

Dr. Tannir: Absolutely, but we must not rest on our laurels. There is ongoing research, including trials combining nivo/ipi with adenosine receptor inhibitors. We are also anticipating more trials in this area. Many investigators are building upon these findings, and we are heading towards triple therapy.

Furthermore, there is a phase 3 trial with 1,650 patients comparing triplet therapy to doublet therapy in the first-line setting. The future looks bright, and I hope our discussion instills hope in patients, emphasizing the ongoing research efforts aimed at breaking the barriers to cure.