Daniel Joyce: Thank you so much. I got to say it's a real honor to be talking about this with somebody who I consider to be a real thought leader in the field in this area in particular. So thanks for having me.
Ashish Kamat: This whole notion of is it effective when it comes to efficacy rates and then is it cost-effective is something that I've been really looking at for a while, partly because I obviously grew up in India and I do work with the Indian government and other healthcare organizations where this is a huge issue. But even here in North America, Dan, I mean, when we look at the new treatments that are coming out, the new combinations, sometimes you look at the numbers and it's staggering. How are we going to sustain this in the United States? And there's a lot that we can talk about, but you've done remarkable work when it comes to looking at the BCG and BCG IO paradigms. It's CREST, POTOMAC, ALBAN. So if you would share with us and the audience your thoughts, your findings, it'd be phenomenal.
Daniel Joyce: Absolutely. I think you make a good point in that there's older data that showed that bladder cancer is the most costliest malignancy per patient lifetime. And that was like from 2011 before any of these treatments came on the scene. So now we have all of these hugely expensive treatments in BCG unresponsive. Now we're starting to move those earlier in the disease space to high-risk non-muscle-invasive bladder cancer. And so the work that we did was just to try to understand what is the real value of these newer treatments, specifically adding immune checkpoint inhibitors to BCG in that high-risk non-muscle-invasive bladder cancer space.
And it's a nice way to look at it, because when you see a positive trial like CREST, POTOMAC, you say, "Well, this is great. We should start using this." But you start looking at some of the details of that trial, which we all as clinicians do and we say, "Okay, 7% EFS benefit at three years. Okay. 30% risk of a Grade 3 or higher adverse event. Okay." Now that, as clinicians, I think has deterred a lot of us in the discussion to say, "Okay, maybe this isn't the right treatment given that toxicity profile."
But for patients, that's a harder discussion to have. And so what cost-effectiveness analysis does in that context is you can contextualize a little bit better for patients. So I can tell a patient, "Listen, the trial, if I run this through a Markov model, which we did, the trial tells us that ICI plus BCG gives you 11 days of perfect health compared to BCG alone." And then when you have that discussion with the expected out-of-pocket costs that are going to come from the adding those treatments, I think it's more tangible discussion with patients.
Now there's another piece of this from the healthcare system side of things, which most people, as you say, in America, write off and don't care about, which is one of my frustrations, in that everybody sees a title that says cost-effectiveness analysis and they're like, "Okay, I don't care. It doesn't matter for my practice." So that's why I start with the patient-centric view there. But I do think there is a reckoning coming in America with these treatments and that cost. And what we try to show is that BCG is really good. It's a high value treatment because it's effective and it's cheap. And so if you're going to go head-to-head with it in a trial from a value perspective, that drug's either got to be really good or there's only so much you can charge for it or should charge for it to make it valuable to our healthcare system.
Ashish Kamat: There's so much then there that we can unpack. I mean, gosh, we don't have two hours to talk about it. But I want to drill down a little bit on that. Because when a patient is sitting in front of me and I know all of the toxicity data, I know that 7%, 5%, 25%, 40%, but the cost is something that sometimes patients almost look upon as, "Oh, why is my doctor worried about cost?" How do you suggest that patients, advocacy groups, and others factor in data such as yours to help improve education of not just our patients, policymakers, but truly everyone that is looking at?
Daniel Joyce: Yeah, it's a really great question and one I'm very passionate about. So I'm trying to do a lot of work to bring price transparency to patients so that when they're making these treatment decisions in the clinic they at least understand what their patient responsibility is going to be from those options, which in my opinion, I think should direct their care. And I think patients would agree with that. They want to talk about costs with their physicians. There's also some interesting data we found in the prostate cancer setting where patients had a guilt associated with using some treatments that they knew were very expensive to the healthcare system despite them having very low out-of-pocket costs from that treatment. So I don't think we think about that as clinicians enough that patients who are undergoing cancer care, they understand the resources that are being poured into them to give them these gains and recurrence-free survival, overall survival.
My personal belief is that we should alleviate that burden from them. I don't think that's their responsibility to feel that. I think we, as clinicians, need to feel that burden. And so when patients want to talk about costs, in my mind, they want to talk about it, how it's going to affect their life, which is a toxicity of that treatment. Financial toxicity is something we, as clinicians, need to start getting comfortable discussing with our patients. But from the healthcare system's perspective, I think we for too long as clinicians have buried our head in the sand and said, "That's not my problem. If Medicare wants to reimburse this, I'm going to go ahead and use it in my clinic." Well, I think we got to be a little bit more responsible and start thinking about the healthcare system as a whole. Because eventually if we don't start taking the reins, I think somebody else will and we'll have less control in that conversation. So I think the time is now to really start thinking about these things from a healthcare system's perspective as we're using these treatments in our practice.
Ashish Kamat: So it's interesting what you said earlier about the patients and the guilt that they feel. Because here, right before the AUA, we launched a bladder patient burden survey at the National Press Club. And one of the things we heard from patients is the guilt that they feel talking to their physician about things that truly matter to them. And one of the things that they also felt was that the doctors may not be actually spending enough time talking to them about the nuances of the treatment, including, and it could be cost and other things.
But I also want to get back to something and I'm probing here a little bit, so feel free to not answer if you don't want to. When we talk in academia, we all are like, yes, cost, cost, cost. For example, BCG-responsive space, Gem/Doce, cost-effective, very efficacious. When I talk to my colleagues out in the community and they're excellent clinicians, but they have to worry about their private equity or whatever practice is running it that tells them, "Hey, choose the most expensive drug because the company makes more money." And when I'm talking about pharma, I'm talking about the private equity for the practices. How are you in what you're doing trying to address that?
Daniel Joyce: This is going to sound a little bit controversial, but I think you can play both of those worlds. So I'd encourage you to look in your practice of your reimbursement for the current BCG unresponsive drugs and we're talking about a different space here. But I think you'll find that, Adstiladrin, Anktiva, all these different treatments, they're going to be reimbursed a little bit differently and then your margin's going to be a little bit differently for those. Now we have no head-to-head data comparing any of those to know which one's superior to the next. And so is there a place for the monetary support of your institution to play a role in how you sequence those if you're going to sequence those treatments? I don't know, maybe. The ethics of that are a little less outrageous than in treatments where we know one's better than the other and we're going to choose the more expensive one.
I also think, from a clinician's standpoint, the number one goal should be on the patient and what is going to affect the patient. So I think if we have a hierarchy of how we're going to give treatments and consider costs, the patient comes first in everything. And so you're going to try to choose the one that is the best for treatment of their cancer, but within the confines of what they can afford and what is easily accessible for them and what they're going to be compliant with and adherent to. That doesn't necessarily mean that beyond that, you can't actually think about these treatments in the way that they are financially benefiting your practice. And like you say, I think that's happening whether we like to believe it or not. And when you have clinical equipoise between treatments, then maybe there is some role for that. So I'm not as pessimistic about that outlook as maybe I should be. But I think in this space where we don't have better data to guide management, I think it can be a piece of the decision making.
Ashish Kamat: I think that's a critical point. And in closing, I just want to say, I think kudos to all the investigators and patients participating in these large studies that give us the data that then you can analyze for cost-effectiveness. It doesn't take away from the fact that these studies were done, that they have shown that there is more efficacy. But I think factor in the cost to the patient, the financial toxicity to the system is absolutely critical.
Daniel Joyce: I could not agree more and it's an area we really need buy-in from patients and from clinicians researching it. So these Markov models that we use for cost-effectiveness, they're always viewed through a healthcare system's perspective. But it would be very easy to take that same framework and put it in the context of the patient. But right now, the data we have aren't good enough because we're not studying it well enough. So what are the out-of-pocket costs of the treatments? We need good data to show us what the trade-offs are there. What are the indirect costs of these treatments? How does doing monthly Gem/Doce maintenance compare to three treatments of BCG on that schedule? How much are they driving? What can they expect from that? All of these things can factor into this model in a way that could be packaged for a patient to really, really understand what are the trade-offs of these treatments individualized to them and that's where we need to go.
Ashish Kamat: Absolutely. Thank you so much for taking the time.
Daniel Joyce: It's my pleasure. Thanks for having me.