Comparing IO/TKI and IO/IO First-Line Treatment Regimens in Advanced RCC

EP: 1.Lenvatinib Plus Pembrolizumab Versus Sunitinib in Patients With Advanced Renal Cell Carcinoma (aRCC)

EP: 2.Pembrolizumab Plus Axitinib Versus Sunitinib for First-Line Treatment of Advanced Clear Cell RCC

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EP: 3.Comparing IO/TKI and IO/IO First-Line Treatment Regimens in Advanced RCC

EP: 4.Selecting an Appropriate Frontline Treatment Regimen for Patients With Advanced RCC

EP: 5.Treating Patients With Metastasized RCC

EP: 6.Managing Adverse Events in Patients With Advanced RCC Receiving an IO/TKI Combination Regimen

EP: 7.Atezolizumab Plus Cabozantinib Versus Cabozantinib Monotherapy for Metastatic RCC

EP: 8.Emerging Advancements in the Treatment of Clear Cell RCC

EP: 9.Recent Data Updates in the Treatment of Non-Clear Cell RCC

EP: 10.Cabozantinib Plus Nivolumab and Ipilimumab for Advanced Non-Clear Cell RCC

EP: 11.CONTACT-03: The “Most Important” Data Readout in RCC From the 2023 ASCO Annual Meeting

Robert Motzer, MD: There are now three different trials with various TKI IOs that show this really high level of efficacy with response rate and long progression free survival and this survival benefit. And though I don't think you can necessarily make cross-study comparisons to, say, one particular IO/TKI combination is better than another, they all really complement each other in saying, "Yes, this is a very effective approach for the first line treatment of advanced RCC." Now, Dr Rini, what is your kind of take on the controversy between use of these in first-line therapies and ipilimumab-nivolumab?

Brian Rini, MD: We've been talking about IO/TKI versus IO/AO for three, four- I'm losing track of the number of years we've been debating and discussing this. And I think ipilimumab-nivolumab is a great regimen. Some initial toxicity, and plenty of patients who just simply can't tolerate ipilimumab. But if you take the patients who are able to get that therapy, the greatest calling card of that regimen is if you respond, it's very likely to be durable. And that the Kaplan–Meier of their duration of response is quite impressive and the tail is over 50%. It was 56% or something at five years, if I'm remembering the numbers. So clearly, if you respond to immune therapy, you tend to do so durably. If you respond to dual immune therapy, not surprisingly, you tend to do so really durably. And this is not on a much greater scale. It's not dissimilar from the hydroxyl 2 discussions we had 20 + years ago, it was a small subset of patients, but they benefited wildly. This is clearly a much higher subset of patients, but durable benefit is there. As you both said, IO/TKIs have a lot of advantages. Number one, they're easier to give, certainly upfront. Although the chronic TKI toxicity can be an issue. We can talk about how to manage that. A lot of tumor shrinkage. It's pretty clear when you add in a VEGF TKI to your regimen you control disease better. Primary progression rates of 5 to 10% versus 20% with ipilimumab-nivolumab. PFS out to two years with lenvatinib + pembrolizumab. Response rates up of 70%. CR rates I think lenvatinib + pembrolizumab updated at 18%. So, we're seeing a lot of tumor shrinkage, which has advantages not necessarily in all patients, although all patients want that, but in patients with bulkier symptomatic disease, I think there's clear advantages. So, I think, as you said, all these regimens complement each other. It's good to have more than one choice. I don't know that we need to argue over the best choice because I've used all of them, and in different patients, I might reach for different ones.

Robert Motzer, MD: You make really good points. And I think another one of the benefits of IO/TKI combination is it's not bottled into this risk grouping. I think it's kind of one treatment fits all because the risk groups certainly are somewhat archaic. They're based on rather crude clinical features, and they're not entirely objective. And so, I think that with the TKI IO, there's a benefit across the board. And I think that your efforts and efforts of others have been really important to see if we can kind of tone down, to see which program is better for which patient but do that more on underlying biology rather than one or two of our risk groups.