Ashish Kamat: A warm welcome to all of you to the UroToday studios. I'm Ashish Kamat, Professor of Urologic Oncology at M.D. Anderson Cancer Center in Houston, Texas, and we are live at AUA 2025 here in Vegas. It's a pleasure to welcome Professor Josh Meeks to the studio. Welcome, Josh.

Joshua J. Meeks: Thanks, Ashish. Great to be here.

Ashish Kamat: So you're doing a lot of stuff here at the AUA. One of the things you're doing is actually the NIAGARA study—the updated results from the NIAGARA. So share with us your findings and the survival data.

Joshua J. Meeks: Yeah. So I think the key thing about what we're presenting here is really the disease-free survival data. And how we contrast that with the previously published ITT population is that those were all patients. And, really, any event that could occur in patients that got one cycle—whether that be pre-surgery, where it was patients who couldn't receive all the doses or decided not to have surgery, if they had progression, or they died—those were all considered events.

What we're presenting here is disease-free survival, and those are the pure cystectomy populations. So it's 88% of those in the durvalumab arm and 83% in the comparator arm. So they just had a cystectomy, and the DFS events are those that happen after surgery. So it starts from time zero, at the time of the operation. And, again, it's cancer progression, recurrence, or death.

And so really what we see, first of all, is looking at those who had a cystectomy—so the pathologic response data, 42% in patients that had a radical cystectomy in the durvalumab arm compared to 33% with gemcitabine and cisplatin. The hazard ratio is 1.86. So, again, that is very consistent with a 10% improvement that we saw in the ITT.

But I think a lot of people saw that path response data in the New England Journal paper and said, well, that's not as strong as we would anticipate. But, again, that's the entire ITT population. When you just look at those who had a cystectomy, it was 42%.

Now, the DFS data is also very intriguing as well. So, again, it's a 31% reduction in either recurrence or death after surgery with the addition of durvalumab. So that's a very striking difference.

And in an exploratory analysis, if you look at pCR and non-pCR patients, even if you had a pCR and you had a radical cystectomy, there was a very significant improvement in DFS inpatients when they were on durvalumab after surgery. And that's kind of a sea change, right?

So we tend to think about patients that if you have a path response, then we can just watch you. But really, we're showing a benefit—even in those who had a pCR—to be on durvalumab. And again, that's eight cycles of durvalumab after surgery.

Ashish Kamat: Yeah, I think those are some critical points that you put in there, so let's unpack some of it a little bit. One of them was the criticism that a lot of people put on the pCR rates, saying that it's inferior and it's not as good as what we have standard of care. So how can you use this as a comparison? So it's good to look at these actual patients that got the therapy. Obviously, for a trial, ITT is the way to report it, but it's great to see this data.

Now, with this data in hand, do you think that this paradigm, the NIAGARA paradigm, let's call it, will supplant the use of dose-dense MVAC, for example, in academic centers?

Joshua J. Meeks: I think the challenge really comes from trying to compare across trials. So when you compare like VESPER to NIAGARA, there are some differences.

So, first of all, with NIAGARA, 60% of the patients were T3 or greater, so that was a much higher stage than what was in VESPER. And again, in VESPER, the path response rate was only those patients who had a radical cystectomy, whereas that's what we're presenting here today. So that 42% is really the same. And, again, it's a higher-stage population.

I think the other benefit is GC-durva. If you look at the side-effect profile and the tolerability, it's much better tolerated for most patients. That's why in the US very few people actually give dose-dense MVAC because of the tolerability. Whereas, if you look at the NIAGARA regimen, again, perioperative durva is very well-tolerated.

Ashish Kamat: Yeah. No, absolutely. I mean—but that's a criticism that a lot of people will levy in the academic centers. And, full disclosure, at MD Anderson we use a lot of dose-dense MVAC, and the NIAGARA protocol hasn't caught on because the data had not been presented. So this data that you presented is very valuable.

The other thing is the toxicity profile. So expand on that a little bit. In patients who got durva after cystectomy, what was the time to onset of durva, and what was the time course of the toxicity events?

Joshua J. Meeks: Yeah. So the toxicity really was not different in patients after surgery—really pretty minimal. So the time—the average timeframe was around eight weeks. Less than 2% were longer than 120 days, and realize that much of this was actually going on during the pandemic. So when you looked at time from randomization to surgery, time from surgery to adjuvant therapy, really, it wasn't really affected, as well as surgical complications.

I think the other part that really is going to come out from this is that we—in NIAGARA, we included around 20% of patients that had reduced renal function—so a GFR of 40 to 60. And those are folks that many medical oncologists are not really considering for perioperative therapy.

Again, in this case, it was capped at 20% in NIAGARA. And, in this case, most of those patients got split-dose cisplatin. So, again, we look at the path response rate, and that was also significantly greater in patients who had durvalumab. I want to say it was in the neighborhood of around 36%.

So that data looks very good. The event-free survival also is just as good as the ITT. So in patients with reduced GFR, it means they can get therapy, and they do really well.

Ashish Kamat: And kudos to the folks that designed the trial and to you. Because having those patients with reduced GFR on an actual study like this is something that gives us the data and the confidence that we can actually use this. Because otherwise in the clinic, we're looking to use it, but you don't actually have the data to discuss it with the patient.

Joshua J. Meeks: And the safety profile is also very good. So, again, you worry about can you get those patients through therapy? And now that 40 to 60—that becomes a new bar that people can consider. So it really is good for our patients.

Ashish Kamat: Now, I forget the number of variant histologic subtypes that were in there, what they were capped at. Could you shed some light on that subgroup of patients?

Joshua J. Meeks: Yeah, I'd have to go back and look. I want to say the variants were allowed. As far as the individual ones, the study wasn't really meant to look at that. In the subgroups, there did tend to be a trend toward improvement across that. But as far as individual variants, those weren't centrally reviewed.

Ashish Kamat: OK, great. So, in summary for our audience, your key takeaway from the data.

Joshua J. Meeks: Yeah. So, again, disease-free survival—31% improvement in recurrence, progression, or death after cystectomy; improvement across pCR and non-pCR subgroups; and, again, the path response rate in patients who had a cystectomy of 42%. I think those are the big points that drive this home. And, again, that's why NIAGARA was approved by the FDA and is a category 1 recommendation now by the NCCN.

Ashish Kamat: Absolutely. Well, thanks so much, Josh.

Joshua J. Meeks: Thank you.