Comparing Cost, Tangibility, MOAs, and Numbers: Apples and Oranges

In the fifth part of this roundtable series, the panelists — though admitting it is like comparing apples and oranges — compare the patient logistics as well as different targeted mechanisms of action of different therapies.

This panel includes 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:
I think a really good point, as you brought up, the term personalized care in terms of actually disease characteristics. I think that’ll also come in account in terms of therapeutic interventions, cost, the scheduling of what type of interventions are required, follow-up that’s required, obviously side effects. Just as you said, it’s very difficult to compare because the studies themselves were not identical. They tried to get a very similar, in terms of disease cohort, so you’re not supposed to compare them apples to apples, oranges to oranges.

But of course, that’s what we do. As a simple urologist, I just like to look at simple numbers, so if you break down at the one-year mark, the complete response, you have roughly about 20% with systemic therapy with pembrolizumab; 25, 26% with nadofaragene, with ADSTILADRIN. It bumps up to probably 38, 40% at one year with ANKTIVA, the N-803, and then you get a bump up to probably rough, back-of-the-envelope calculations to probably about 60% plus at one year with TAR-200.

Now, that’s only been … That data hasn’t been published. That was what presented at ESMO, so you do see this kind of, again, not fair comparison, but if you lay it out, different delivery mechanisms, different agents, different types of mechanisms of action, you do see at least, just as you said, Tam, there seems to be less of a drop-off in terms of the response. That might be due to the continuous delivery. You’ve got exposure to the chemotherapy agent, the gemcitabine, basically continuously as you change the pretzel out every three weeks.

Let’s talk a little bit about side effects, and then I want to talk a little bit about kind of intravesical therapy, placement of devices, giving the medicine itself.

Looking at the side effects, the systemic side effects with cetrelimab are not different from any other immunotherapy. Is that right?

Maria Teresa Bourlon, MD, MS:
Yeah, it doesn’t seem it’s not different, and the response rates are not different either.

Dr. Chang:
Yeah, you see basically consistency of, yeah, there’s a little signal, there are a few side effects, nothing that seems to stir the pot too much. When you look at the side effects with the intravesical pretzel agent, Tam, was there anything that stuck out?

Guatam Jayram, MD:
No. Urologists are fairly comfortable with managing intravesical toxicity. I would say that the pretzel can have slightly a different tox profile than say BCG or nadofaragene because there is something that retains in the bladder. It’s rare, but in addition to the lower urinary tract symptoms that we know about, there are some patients, and it’s a small group, but there are some patients that I would say have almost like a stent discomfort type of pain because of the retained agent and retained body into the bladder. That tends to be rare. You can generally [inaudible 00:03:45].

Dr. Chang:
Are there any strategies that you or your group employ in terms of some of those side effects?

Dr. Jayram:
Yeah. Again, remember in the trial, I think it was 6% of patients had to discontinue pretzel only. Again, small numbers, but 6% is still something. Anticholinergic, antispasmodics, topical pain treatments like peridium, alpha blockers for men, those treatments generally help. I think also what you have to realize or remember about this group is this is a heavily pre-treated group of patients. 12 to 15 prior BCG installations. Their bladders are beat up, they’re inflamed. These patients have sensitive bladders, and so that makes it a little bit more challenging. Make sure you’re ruling out infection. Antispasmodics, alpha blockers has helped us.

I think it does need to be said that there are going to be a small percentage of patients that say, I don’t like this right now, and we’ve actually utilized a technique, I don’t know if you even call it, of intermittent, just removal of the pretzel. Just give them some time to wash it out. Then we’ve had several patients that we’ve reinserted it in, and they’ve actually been better.

I think you’re going to start seeing some of these strategies emerge. Some patients never say a word about it, they don’t even know it’s in there. Again, similar to our experience with patients with stents. I think we’re going to start to identify some strategies to help some of these other patients keep it in. It is something that needs to be discussed with the patients. I think the burden of this disease is significant. You talk about catheter installations, and patients coming into the office, and UTIs and all the stuff that they deal with. My oncology nurse has a little drawing that she gives to patients who get various therapies on what their touch points look like over the next 12 months, whether it come in for the installation, come in for the system.

Dr. Chang:
Share that with me. I’ve never seen that. Come on, hiding the goods.

Dr. Jayram:
I credit her. She’s terrific. I think it’s important because it’s really a quality of life thing, and for a lot of patients that are coming from a hundred miles away. Are you going to have to come every such, and so with the pretzel, I think it’s going to be similar. You’re going to have to draw that out and say, you’re going to have to come every three weeks. We’re going to do a cysto here. that is going to be a part of this whole discussion as well. How often are the patients … You’ve mentioned some other agents that have different dosing strategies. That, I think, is important, but overall, we have been involved with quite a few patients on trial across the TAR spectrum. It’s unusual for a patient to have really bad local side effects, but it does happen.