Jeannie Hoffman-Censits: Sure. Well, thank you so much for highlighting this publication. My clinical practice is solely in the care of patients with locally-advanced and metastatic urothelial cancer, so as you can imagine, I use quite a lot of enfortumab and pembrolizumab for that group of patients. And our team was early adopters of the use of ctDNA in this population and in others, and one of the patterns that I saw emerge early on was kind of different tumor dynamics, or different ctDNA dynamics, depending on outcomes to enfortumab and pembrolizumab, and that's really what this publication is highlighting.
Tian Zhang: Yeah, so the circulating tumor DNA assay that you used was, I think, the Signatera assay?
Jeannie Hoffman-Censits: Yeah, yeah, yeah, so there's a lot of commercial products that are available, and our institution is using the Signatera assay for patients in the perioperative setting, as well as those who are getting immunotherapy for monitoring MRD.
Tian Zhang: Yeah. So, tell us about the performance of the test itself and what you saw as you treated these folks with EV pembrolizumab.
Jeannie Hoffman-Censits: Sure. So as you know, this is a commercially available test that we're using in clinics all the time, and in general, we try and get the test prior to patients starting frontline therapy, or around the time that they're starting frontline therapy. We've certainly noticed that patients with metastatic disease can have a higher level of baseline Natera testing numbers, and that there's kind of a different pattern of outcomes to the sequential analysis of Natera ctDNA in this population of patients. What we notice is that patients who have a complete response radiographically will have an immediate change in their Natera, going from a detectable level down to zero pretty rapidly. And in our cohort of a little over 40 patients who were treated with EVP, actually in any line setting, those that had a complete response had a pretty quick time to going from detectable to undetectable ctDNA. We also noted that in those patients whose ctDNA went from detectable down to zero, if they had sequential zero ctDNA over time in each of their subsequent draws, they were more likely to have a CR, and to have better outcomes in terms of PFS and trending towards survival as well.
Tian Zhang: That's great. What did you find for the advantages or disadvantages of using this Signatera assay? How did your patients respond to those numbers?
Jeannie Hoffman-Censits: Sure. Well, I think that patients, especially because they can have access to those numbers, and that we can get ctDNA much more quickly than we can in terms of getting imaging studies, that patients appreciate having kind of an early sense of what's going on with their disease, as well as it seems that the Natera ctDNA values, and again, depending on the cadence with which patients are getting these values done, they will preempt what you're going to see on radiographic imaging. So, we certainly see those ctDNA values in the patients with best outcomes, long-term CR, coming down to zero before imaging sometimes will change or become that CR. So, we were finding quite an interesting early signal of outcomes to EVP.
Tian Zhang: Yeah, that's great. What do you think, in the community, is this ready for prime time? Should we be sending Signatera assays on our patients starting EVP?
Jeannie Hoffman-Censits: Signatera is approved for patients both in the perioperative setting and for patients with any solid tumor on immunotherapy to measure outcomes to immunotherapy, so I think it's out there and people are using it in different ways. Our study was certainly a hypothesis-generating study, and man, look around here at GU ASCO. There's several different studies looking at different kinds of questions. But I think again, in the EVP setting, how to use and how to interpret these Natera numbers with kind of, I think, similar messaging of what that looks like. But like any clinical study, we're getting it at different times, different cadence values. But I think having a baseline ctDNA done and looking at those numbers over time will be an important tool in our toolkit, but I think there's a lot more to learn, and we look forward to seeing ctDNA incorporated much more in prospective studies and seeing what those outcomes look like. I do think it's going to be an important tool ongoing.
Tian Zhang: Great. Any further takeaways for our audience today?
Jeannie Hoffman-Censits: I think that we're certainly in a different time than we were quite a few years ago in terms of how well patients are doing with advanced urothelial cancer. I think it's a really hopeful time. And I think the more tools that we have to understand how to better drive these therapies, EVP as well as the other therapies that are coming down the line, in terms of how long to keep patients on and thinking about sequencing them, and especially those patients who may not be getting the benefit that we hope for with EVP, I think having all the tools that we can at our disposal to help those patients will be really important. So, I think there's a lot more to come with this technology.
Tian Zhang: Awesome. Well, congratulations on your publication and finishing this important study. I think for our metastatic population, it'll help us all manage and help guide our patients getting enfortumab and pembrolizumab.
Jeannie Hoffman-Censits: Right. Thank you so much.