Where We Were and Where We Are in NMIBC Trials and Therapies

In the third part of this roundtable, Gordon Brown, DO, Tim Richardson, MD, Bryan Mehlhaff, MD, Chris Pieczonka, MD, and Gene Cone, MD, explore advancements in treating high-risk, non-muscle invasive bladder cancer (NMIBC), focusing on the BCG-refractory population. They discuss the evolution from early therapies like valrubicin to more recent options, including pembrolizumab, nadofaragene firadenovec, oportuzumab monatox, and the TAR-200 device, which offers extended intravesical gemcitabine delivery. The panel examines improved complete response rates, manageable toxicity profiles, and strategies for mitigating lower urinary tract symptoms. Emphasizing patient education and practical management approaches, the discussion highlights how these innovations enhance treatment outcomes while maintaining quality of care.

Watch part four of this roundtable series: SunRISe-1 Data: Benefits of the Pretzel Device and Gemcitabine Monotherapy

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Dr. Brown:
So let’s switch gears a little bit and talk about some of the trial results that we’ve seen in patients with high-risk, non-muscle invasive disease. We’ll focus primarily on the BCG refractory spectrum, but we’ll kind of walk through where we were to where we are, right? Valrubicin, it’s just, as a kind of disclaimer, right, we shouldn’t really cross trial compare, but we all cross trial compare. And we’ll dig down into the weeds a little bit as to why that’s probably not always valid. Design’s an issue. How do we define CR, all those kinds of things, whether it’s biopsy driven or cytology scan driven, et cetera. We can walk through that as we go along. But where we were, right, back in the day, we had Valrubicin, right? We had maybe a 9% or less CR rate, then we had Pembroke come onto the scene, right? That gave us a 12-month CR somewhere in the 19% rate roughly.

Then we saw the approval of Instillogen, right, with maybe 25% roughly back of napkin math, CR rate at 12 months. And then we saw Activa, which is looking in the mid-forties in terms of that 12 month CR. And now we have most recently reported ESMO in 2024, which I actually didn’t attend. But kind of looking at the data, we have the SunRISe-1 trial reporting out, right? And here we have a TAR-200 device, which is really looking at really some compelling results. So why don’t you walk us through first what the TAR device is, Chris, why don’t you talk about that a little bit?

Dr. Pieczonka:
So I think that if I was explaining what the TAR device is to the patient, number one is I say, it’s not immunotherapy. So I think patients understand the concept of doing something on the inside of their bladder. And I use the term pretzel. So what this is this is a drug delivery device that has medicine delivered into the bladder over a couple week period of time, and then it’s fished out and then you put a new one back in. And explain to them the side effects are typically more related to the bladder itself rather than sort of systemic type of side effects. So that has been a pretty easy sell. We’ve had the fortune of being able to participate in several of the studies. In terms of patients understanding the concept of what that means for their overall sort of cancer care.

And I think what Gene was saying is that I think that they understand that you can put fairly obnoxious medicines into the bladder and not have that systemic crossover. That’s an important thing because I know that they’ve done studies that show that you’re not getting the medicine in the TAR-200 device into the bloodstream. So that’s an important factor for the patients to realize that it’s not systemic therapy.

Dr. Mehlhaff:
Maybe just the additional, I think patients would understand that you come in, we put medicine in your bladder, we ask you not to urinate for one or two hours, and then we do it again at some interval. Now this is more of a continuous therapy and I think patients would understand that, yeah, that sounds like a good idea.

Dr. Pieczonka:
Yeah.

Dr. Brown:
Yeah. I think you bring up two good points. One, I describe it as a pretzel too, and why? Because it looks like a pretzel, right?

Dr. Richardson:
It looks like a pretzel.

Dr. Brown:
So I’m a urologist, I’m not a rocket scientist. So I describe it as it looks, and I think that’s easily consumable both by my colleagues as well as by my patients, one. Two, you’re speaking a little bit to mechanism there, right, Bryan, in terms of exposure to the urothelium of a therapeutic. And does that… Well, one, we have to be concerned on AE profile in that context, right? Because it is gemcitabine, right? And two, does that speak maybe to some of the results that we may see with this? What are your thoughts, Gene?

Dr. Cone:
Yeah, I think that the extended duration of the release has to be playing a major role in the results and the fact that the complete response rates that we’re seeing are so much better than intravascular chemotherapy has demonstrated in the past, at least in single-agent intravascular chemotherapy. So, it has to be something related to the duration of action.

Dr. Brown:
Yeah. And that at least I guess conceptually would be that you’re storing this in there for a three-week period of time, then it’s getting exchanged out for at least on trial that was up for 24 weeks. And then whereas with traditional intravascular therapies, you’re voiding them out within two hours. So the exposure to of a desired therapeutic mechanistically is going to be much more prolonged. And toxicity-wise, toxicity profiles seem pretty reasonable. Right? We’ll walk through the results in a second, but have you guys had any issues on trial with management of toxicity in this patient population and have you developed any strategies? Are these toxicities that we as urologists can manage?

Dr. Richardson:
I think our toxicity, it’s been manageable, number one, it’s definitely more than BCG.

Dr. Richardson:
Maybe more than Gem/Doce, probably because it’s constant dwell time, constant contact, which is a good thing from an efficacious standpoint, but it’s all manageable. It’s mostly overactive bladder, urgency frequency, some dysuria. I’ve only had one patient in all the trials that we had a problem with, and honestly, it was mostly psychological-related. It wasn’t necessarily bladder-related.

Dr. Cone:
Do any of you guys prescribe antispasmodics prophylactically for your trial patients?

Dr. Richardson:
I know a lot of people that do. We haven’t started doing it prophylactically. We’ve educated the patient that let us know if you start having problems with this, and we can start it, but it’s reasonable. Yeah.

Dr. Cone:
Our experiences was that we started out doing that because we were concerned for some of the earlier Sunrise trials, and now we’ve kind of gotten away from it because most patients, that doesn’t really seem like they need it.

Dr. Richardson:
Okay.

Dr. Pieczonka:
Well, I think what Tim said is something that’s interesting about the potential psychological sort of effect on that, because I think that it appears to me that people get, quote-unquote, used to the side effects. And is that because it’s better or is it because we’ve educated them better after a couple cycles and then pulling the trigger on something sort of benign from an OAD standpoint, it’d be pretty easy to. But we have the same experience. I haven’t had anything that was not manageable in terms of local side effects, dysuria, et cetera, that we couldn’t handle within clinic. And these people are not calling at night. There’s not emergency room visits for this. So I think that the adverse events that are seen are phone calls that are able to dealt with during the course of the business day, patients coming in and being seen without having to go to the ER.

Dr. Brown:
So strategies like maybe a beta-3 agonist, things like maybe some pyridium, maybe an anticholinergic depending on whatever fits that practice patterns, having some strategy at hand to mitigate it sounds like lower urinary tract symptoms, which are part and parcel of intravascular therapies. Things that as urologists we’re extremely comfortable managing.