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Ricky Dylan Frazer: My name is Ricky Frazer. I'm a consultant medical oncologist at Velindre Cancer Center in Cardiff in the UK. And over the next few minutes, I want to explore our paper to tivozanib monotherapy in the frontline setting for patients with metastatic renal cell carcinoma, and favorable prognosis which is published in current oncology reports. Now, as of 2025, we know that there are three main options across the risk groups in the frontline setting, this is immunotherapy and immunotherapy combinations, otherwise known as IO-IO, immunotherapy plus TKI combinations otherwise known as IO-TKI or single agent TKI.

There are many factors that influence decision making, and we explore this in the paper, this includes the IMDC score, but also the outcome endpoints and potential side effects or toxicities. When we think about the favorable risk group, we know that IO-TKI in combination does improve PFS and response rate compared to TKI monotherapy, and therefore for some patients, it's absolutely right that they should be given IO-TKI. In the intermediate and poor risk group, we know that both IO-IO and IO-TKI combinations have demonstrated improved survival.

But despite many IO-TKI frontline trials versus single agent in the favorable risk, this improves survival has not been replicated. And therefore we think TKI monotherapy remains a valid option, particularly in these favorable risk patients. In this article, we focus specifically on tivozanib, we know that the favorable risk patients tend to be more angiogenic, and so biologically, there's a good rationale for favoring a TKI in this group of patients.

We know that age and comorbidity remains important, and there are a group of patients who want to minimize hospital attendances, both for review and for treatment. And we also know that with immunotherapy, there are both life threatening toxicities and permanent toxicities that can happen, and some patients wish to avoid this risk altogether. Single agent TKI unfavorable risk is supported by international guidance, such as ESMO, EAU, and the NCCN.

And if we look at the drop off rates in some of the real world data, in particular in the UK renal oncology collaborative or UK ROC publications, we can see that the drop off rate between first line and second line is less in favorable risk group compared to the pawn intermediates, and therefore more favorable risk patients can receive IO in the second line if they are favorable risk. Now, if we're comparing the different TKIs in terms of efficacy, the trial data that we've got available, and indeed the real world data would suggest that efficacy is comparable, and this is demonstrated in table 1 of the manuscript.

If we focus on the phase III TIVO 1 data, PFS was 11.9 months. And in a subgroup analysis focusing on the favorable risk group, the hazard ratio between tivozanib and the comparator arm sorafenib, was an impressive 0.39. We explore in the paper a recent meta analysis of the TKIs, which show this comparable efficacy, but shows that tivozanib has the most favorable safety profile. And in this paper, we review real world data from a number of countries that support this view.

As tivozanib only targets the different VEGF receptors VEGFR-1, 2, and 3, and doesn't target things like FLT3 or platelet derived growth factor receptor, and indeed met, it has less off target effects such as diarrhea, fatigue, and hand and foot. And therefore, to conclude, we believe that there's a proportion of favorable risk patients with single agent TKI should remain the standard of care. And based on efficacy and safety and indeed international guidance alongside real world data, it supports the use of tivozanib in this patient group. I hope you enjoyed the read.