Frontline RCC Treatment Selection: IO/IO Versus IO/TKI

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 first segment of the roundtable series, the panel weigh the treatment considerations of IO/IO versus IO/TKI.

Watch the next segment in this series.

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Dr. McKay: Thank you all for joining us today. We are here with GU Oncology now, and we are just finishing up day 3 of ASCO GU 2024, our 20th-year anniversary. It is a big year for us with lots of exciting data presented in kidney day, spanning from adjuvant to advanced disease.

So, I am really glad to have you all here with us. Let us just dive right in before we get into the data. Let us talk about frontline. Where are we at right now? What is your practice? How do you approach the different options we have, from IO/IO, IO/TKI, to the various VEGF options and observation?

Dr. Beckermann: I would love to hear what Dr. Tannir has to say, but I think the continued data updates, such as Checkmate 9ER with its 55-month median follow-up data and CheckMate 214 with 8-year survival data, are crucial. They are the only data showing improvement over time in those good-risk, favorable-risk patients.

When I am thinking about the patient and aiming for a cure, I consider factors like the IMDC criteria and long-term survival. However, we must remember there is an individual patient sitting in front of us. For those with high visceral disease, the upfront decision remains a challenge. I tend to focus on whether I can rescue them with a TKI if they progress, aiming for a durable cure and treatment-free survival. There is still a population of patients with aggressive biology, where I may opt for a combination of angiogenesis targeting and IO to prolong their survival, although the upfront ORR is higher. I was particularly pleased to see the data from Checkmate 214.

Dr. McKay: Dr. Hammers, what is your current approach? How do you select patients for IO/TKI or IO/IO?

Dr. Hammers: I agree with Dr. Beckermann. The primary goal is cure, and we are fortunate in RCC to have immunotherapies with significant responses. My preferred regimen for best long-term outcomes remains dual immune checkpoint inhibition with nivolumab/ipilimumab. The main question I ask is whether a VEGF TKI is necessary, especially for patients with symptomatic large disease burdens where progressive disease could lead to a poor outcome. In such cases, I may opt for a PD-1/TKI regimen. However, the majority of my patients are candidates for nivo/ipi. Additionally, we must consider the heterogeneity of responses and potential consolidation therapies like SBRT or surgical resection. After nivo/ipi, if necessary, I proceed with VEGF TKIs or similar therapies for palliative care.

Dr. McKay: How do you integrate IMDC criteria into your decision-making?

Dr. Hammers: I do not prioritize IMDC criteria much with immunotherapy. Dr. Tannir has shown us that for favorable-risk patients, this might be the preferred regimen for long-term outcomes. We need to rethink our approach for these patients.

Dr. McKay: Dr. Tannir, what is your approach to frontline treatment?

Dr. Tannir: I echo the sentiments of Drs. Beckermann and Hammers. For patients with high tumor burden and symptomatic disease, I may opt for a TKI initially for quick debulking. However, I have seen impressive tumor shrinkage with lenvatinib/pembrolizumab, making it my preferred regimen for rapid response. Despite being an immunophile, I usually start with nivo/ipi for the majority of patients, as my aim is to cure them. For those who cannot tolerate induction therapy or progress, I explore other options until we find a durable solution. The latest data from Checkmate 214 is changing our perspective on favorable-risk patients, showing promising outcomes with nivo/ipi.

Dr. McKay: I agree with all my colleagues here that favorable-risk patients often have low burden disease and can afford further treatment if necessary. It is encouraging to see this evolving data.