What Does the Pipeline of Data Traveling From Large Meetings to the Community Setting Look Like?

In the third episode of this roundtable session, Drs. Chang, Qin, Jayram, and Bourlon chart out the route that data makes down the pipeline from clinical trials/academic-setting practices to community-setting practices. They discuss the TAR-200 intravesical device in trial and how the pretzel device can shape the treatment landscape moving forward in both clinical landscapes.

Panelists in this NMIBC series include Sam Chang, MD, MBA; Vanderbilt University Medical Center; Qian Janie Qin, MD, UT Southwestern Medical Center; Gautam Jayram, MD, Urology Associates of Nashville; and María Teresa Bourlon, MD, MS, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán.

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Sam Chang, MD, MBA:
We learn a lot about new data from large meetings. And the large meetings always fight for important findings. We’ve got, from a urologist standpoint, AUA, from the medical oncologist standpoint, ASCO, ASCO GU. Most recently we’ve had ESMO in Europe. It’s a nice chance to go overseas, get a little, probably a little food, a little wine. But most importantly to learn about what’s the latest in terms of the data that comes out. And obviously different studies mature at different time points. And so for us, for myself and for urologists in the US, we don’t often get the information from these trials that occur outside or more medically oncology derived. So most recently at ESMO there was data regarding, we’ve talked about the pretzel, which is part of this TAR-200. And there are looking at actually different types of patients specifically for BCG unresponsive disease.

So I personally wasn’t at ESMO, but I was wondering if any of you all want to talk a little bit about the data, looking at SunRISe-1, which is actually a treatment of those patients that were BCG unresponsive. And there were actually four different cohorts, but they focused on three. One cohort was actually the TAR-200, which is a unique delivery device. The urologists are simple. We call it the pretzel. And how do we remember it? Because it looks like a pretzel. So as a result, we know that’s a special delivery agent that has, impregnated in it, gemcitabine. Another cohort was actually a systemic therapy, cetrelimab, which is actually along the lines of a PDA, a PD-1 inhibitor. Maybe PD-1 or PD-L1, obviously, I don’t remember, but it’s an immunotherapy. And then the combination of those two. Cohort four was the papillary disease, which wasn’t reported. So who wants to start and tell us a little bit about SunRISe-1 and what was presented?

Maria Teresa Bourlon, MD, MS:
I’m happy to go ahead. I think the importance of SunRISe-1 is it’s giving us the TAR-200, which is an intravesical delivery system for gemcitabine. It changes every three weeks until week 24, which is something we need to contrast with other intravesical therapies that might be given at a longer window of time. So that’s something important. It also provides us, cetrelimab, PD-1 inhibitor, which we might contrast the data that we have with pembrolizumab. But I think it’s very interesting that they did this mix of the cetrelimab with the TAR-200 gemcitabine intravesically. And now it’s astonishing to see that the response rates were not increased with the combination therapy. And the single use of the TAR-200 device was the one who had the highest complete response and the highest complete response at 12 months. So I think that’s something that’s really important. Know cetrelimab had roughly-

Dr. Chang:
We don’t want to put you out of business, but it was intriguing that when we saw that data, looking at it, Tom, from a urologist standpoint, there are big practices, like your practice, that are very comfortable. I wouldn’t say very comfortable, but do treat patients with systemic immunotherapy, understand the side effects, understand the importance of monitoring. But the uptake isn’t as great or universal. And I’m sure that’s also the case worldwide regarding immunotherapy by the urologist as opposed to the medical oncologist. So it is interesting, and I think from a urologist standpoint, the idea that, okay, perhaps we don’t need the systemic therapy and we can treat these patients, at least initially, with an intravesical therapy, is appealing. What do you think about that?

Gautam Jayram, MD:
Yeah, it is really interesting. A couple things stand out to me. Number one, this notion, more is not always better.

Guiding Patients Through Treatment
Unless it comes to ice cream.

Dr. Jayram:
Yeah. Or deep-dish pizza.

Dr. Chang:
Pizza. I’ve had dinner with you and I know you feel very similar about all those things. Absolutely. Okay.

Dr. Jayram:
But really it’s true is we are in this way in oncology of, okay, well let’s stack up all the treatments and see how they respond. And sometimes that really is the best thing, especially for patients who are younger and can tolerate toxicity. But this was really important because, as you said, the uptake, especially in urology of systemic therapy for BCGN-responsive disease has been very low. And there are about 20% of urology practices around the country, large groups who have a lot of infrastructure, who are doing a lot of infusional therapies for prostate and whatnot, have taken this up. And myself and a couple others have been on the front lines of developing guidelines and pathways and helping big urology groups do this. Even then it has not been what you would think. And again, it’s what has been already discussed. It’s not just that the side effects are challenging, but the efficacy is not really what we would hope it would be at a year.

And so that, I think, both of those factors are important. So I think SunRISe-1 was important because really, really high CR rate, and we’ve seen all of these trials read out, and they’re very different trials, so you can’t compare across the board. But we still haven’t seen a CR rate in the 80s. And I would argue that it really goes to mechanism of action and the fact that there is a continuous reception of the treatment by the bladder as opposed to this intermittent treatment that we usually see from these intravesical therapies that are poorly sustained and get voided out. We have continuous stimulation of the bladder by a chemotherapy agent. And it’s really important. And remember, in this trial there was no re-induction. And a lot of other trials in this space, if you are not a complete responder at three months, you’re getting the treatment again.

And then you’re generating what’s called an anytime CR rate, which is a little bit tricky to compare because a lot of the earlier trials just used three months CR. If you didn’t respond, you didn’t respond. So this trial did not use re-induction. The vast majority of the responses were seen at three months, very, very high percentage. And then those continued to respond for a long time. So I think that was really important. And I think it does cast a little bit of doubt on systemic therapy alone, or even the incremental value of adding a systemic agent, because there have been other trials that have read out in this space with combination where you have maybe a five or an 8% increase in your CR with the PD-1 agent, but then you have a significant amount of discontinuation and you have a significant higher side effect profile. And I don’t think, within the urology community, I don’t think that’s going to be worth… The juice is not going to be worth the squeeze.

Dr. Chang:
Yeah, no, I think a good point that the combination arm in the trial had clearly, in terms of adverse event rate, you’re talking in the mid-20s as opposed to single digits. With single arm in either the cetrelimab arm by itself or with the TAR-200 by itself. So the combination seemed to be a little bit more difficult to tolerate, more side effects.