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Sam Chang: Hi, I'm Sam Chang. I'm a urologist in Nashville, Tennessee, and it's always a pleasure when I get to spend some time with some superstars. And Patrick Hensley from the University of Kentucky is truly one of those superstars. I've known Patrick for several years now, ever since he was a resident at the University of Kentucky. And Go Big Blue, is all I've got to say.

So we're going to actually talk a little bit about utilizing different techniques for those patients with BCG‑unresponsive bladder cancer. And we wanted to focus on actually nadofaragene. So first of all, welcome, Patrick. And tell me the clinical scenarios that you consider patients for when you have one of these newer FDA‑approved agents.

Patrick Hensley: Yeah, thanks, Sam, so much for having me. It's a pleasure being here. I think one of the benefits to nadofaragene, specifically, is that it was, as you know, the first FDA‑approved intravesical therapy for BCG‑unresponsive disease. So at this point in time, it's a familiar drug to most of us, from an ordering and approval standpoint, dosing, and dealing with some of the side effects.

In my practice, one of the big challenges is the BCG shortage. So to get to a BCG‑unresponsive state and have access to some of these novel therapies, obviously, you need to have access to BCG. Conventionally, we've moved from BCG to gemcitabine and docetaxel because it's cheap, it's available, it's effective, it's well‑tolerated.

But in select patient scenarios, I'll move straight to nadofaragene. And I think a lot of that has to boil down to the favorable dosing schedule, the quarterly dosing. A lot of my patients—like you see in Nashville and Lexington, Kentucky—are traveling two to three hours for each intravesical instillation, and they really appreciate the kind of efficiency of the Q3‑monthly dosing schedule.

Sam Chang: No question. If you're given the choice of weekly therapies for a certain period of time and then maintenance versus every three months, this will be the treatment. I think when given choices, patients always have an attraction to that favorable schedule. So along those lines, you talked a little bit about setting up the operational efficiency or setting that up. Tell me, are there any nuances with nadofaragene that make it more difficult, less difficult, et cetera for these patients?

Patrick Hensley: Yeah, I think there are two things. One is the stability of the drug. So it's shipped frozen, it's stored frozen. When the product initially rolled out, I think you needed to use it within a very brief period of time.

Sam Chang: Few hours, that's right, right.

Patrick Hensley: If you thawed it. But now, it's stable at room temperature for 24 hours and in a refrigerator for up to a week. So those kinds of issues are a moot point now. We used to have patients travel and see us at the crack of dawn for a urinalysis to make sure they didn't have an active infection, then they would sit around for several hours into the afternoon to get their instillation while the product thawed.

From an operational standpoint, what we've been doing is just having those patients see their primary care doctor or someone locally for a urinalysis, do a quick telephone screen a day or two before their scheduled instillation to make sure that we're good to go. So the patients show up, their drug's already thawed, and we put it in their bladders. But with the initial product rollout, there was a period of waiting and waiting and waiting for those patients to get their thawed product.

Sam Chang: I think getting out the efficiency patterns that you guys have, I think it would be really, really important as you consider how you integrate something, a newer agent, into your practice and the ability to have the pre‑screen done elsewhere. That's a great idea. Not having to wait for the thaw, I think, is also very, very important, especially just as you say, many of these patients travel a long way. They have the one day that they spend in Lexington, here, let's get things taken care of. I think it's fantastic.

Are there any tricks, any tips that you have that you would recommend in terms of the initial instillation? We've noticed that patients tend to have the most difficulty with that first instillation. Then afterwards, they tend to improve in terms of side effects. Are there any tips, like I say, that you pass on to your partners or your providers as well?

Patrick Hensley: Yeah, this was a work in progress for our group. We did not pre‑administer any medications or pre‑medicate any patients for the first few doses. And it was hard for them to reach that hour dwell. So we pre‑medicate for about 48 hours with an anticholinergic, and that has worked very well. Mark Tyson here at the AUA is going to present some data on rectal Valium as a pre‑medication, and I'm excited to see that data because I think anecdotally, it helps as well. We've used it in a few patients.

Sam Chang: Absolutely. He plucked that idea from when he was a fellow with us. It is actually a game‑changer. It has been difficult to get at different times, but I think I've looked forward to seeing his data, because I think it will be very, very helpful for many patients.

All right, let's get into the clinical scenario of—you've had a patient, two different scenarios. You've had a patient after that first instillation that you evaluate. How do you evaluate that patient first? Do you always biopsy them? Do you do a cystoscopy? How do you evaluate the disease?

Patrick Hensley: Yeah, I think, understanding that you're in the BCG‑unresponsive space, you may have—Adstiladrin still may be the first, or second, or third‑line treatment in that disease space. So at that point, we're committed to bladder preservation as much as it is feasible and safe. So I'm not looking to abandon a therapy early. And as in the clinical trial, it's very rigorous. Patients were not allowed to be reintroduced.

I think in clinical practice in the real world, I have several patients with a persistent positive cytology, for instance, in a negative bladder, negative upper tracts, I'm OK giving them another dose or two of Adstiladrin and monitoring for disease progression. And there's also been some recent real‑world data presented at GU ASCO by, again, Mark Tyson's group in the Mayo data. It's an efficacious drug, and in the real world, I think it beats out some of even the clinical‑trial efficacy endpoints.

Sam Chang: I totally agree in terms of that at least another repeated course or instillation, just as you say, especially with the immunotherapeutic drugs—every other one that we've seen, we see additional possible efficacy not only with time but with an additional dose.

Let's take the next scenario in a little different way. You've had a patient who's had a complete response. They've received all four treatments, the yearly—they're doing well, they're tolerating it. What do you do at that point? Do you stop? Do you scale back? To be honest, we varied. So I was wondering what your practice is.

Patrick Hensley: I think it comes down to patient risk tolerance and whether or not we can continue to get the drug approved. I've had no trouble with approvals. And most of my patients who have achieved a clinical CR after a year or so of treatments want to stay on the drug. We don't have any data to inform whether or not we should continue.

And it makes logical sense that, again, in a very high‑risk patient, you're committed at this point to bladder preservation; they're in a disease‑free state. It makes sense to continue some sort of maintenance schedule of the drug beyond a year, and that's what we've been doing. But some patients have elected to stop, and we just surveil them closely as well.

Sam Chang: Yeah, I think it's unclear. Many of the patients being from not far from Lexington—if it ain't broke, don't fix it, and all those—it's one of those things where if they're tolerating it well, the carriers provide coverage, they've seen a benefit. Many of them obviously have had different types of therapies and want to avoid cystectomy.

And I think, obviously, the responsibility is on us, as care providers, to try to ensure as much as possible that these patients, we can try to continue to spare their bladder. But if we've reached that point, you're exactly right in terms of, well, let's do our best to give the treatments the best possibility of working. And then, OK, there are other options. And then there are other things. And so obviously, patients with significant side effects, issues with payment, et cetera, that may alter ultimately what patients get. But I think your point in terms of continuing therapy that shows efficacy only makes sense.

So as we wrap it up, where do you see the next possible steps of nadofaragene in terms of other patient populations, in terms of prevention disease? Tell me what you think may be next on the horizon.

Patrick Hensley: Yeah, I'm excited to see—as most intravesical drugs are moving into the treatment‑naive space and the intermediate lower‑risk disease spaces. Again, with the favorable dosing schedule, I think it's very palatable for a patient to be offered an option for especially intermediate‑risk, kind of multifocal low‑grade papillary disease treatment with nadofaragene. Because we know those patients are at a very low risk of progression. A lot of them are very inconvenienced by the traditional induction 6+3 or 6‑induction‑plus‑monthly‑maintenance chemotherapy.

Sam Chang: And maybe the inconsistency of having that BCG available.

Patrick Hensley: That's exactly right. So I'm excited to see how the drug rolls into the treatment‑naive and kind of intermediate‑risk disease spaces for sure.

Sam Chang: That's fantastic. So, Patrick, thanks so much for spending some time with us, and I look forward to continuing collaborations with you.

Patrick Hensley: My pleasure, Sam. Thanks.