Timothy Lyon: Appreciate the opportunity. Thanks, Dan.
Daniel Joyce: I am a huge fan of your work in the non-muscle invasive bladder cancer space. Looking at specifically how the treatments we give those patients affect their life, and it's not just what they pay out of pocket, it's the impact on the time, the burden of receiving the care that we give, and it is a lot. I mean, bladder cancer, as we know, is the costliest malignancy over a patient's lifetime, and I think a lot of that comes down to a lot of the things they have to do to receive care. You've done a lot previously, looking at both the feasibility and patient acceptance of doing these intravesical therapies at home. Now you're starting to look at it in more of a trial form, in the INVITE trial. Can you tell us a little bit about what you're doing and why you're doing it?
Timothy Lyon: Absolutely, appreciate the opportunity to talk about our work. All right, so we have currently opened what we are terming the INVITE trial, and in-home trial of intravesical therapy delivered in patients' homes. The reason that we're doing this is we know that intravesical therapy for non-muscle invasive bladder cancer is very burdensome. It requires six weeks for induction therapy, maintenance therapy periodically, depending on regimen, along with periodic visits for cystoscopic surveillance and upper tract imaging. As you can see on the right side of the screen, if a patient were to perfectly follow the SWOG maintenance protocol for induction and BCG, they would need 19 visits to the urologist in the first year after diagnosis. This is occurring in an older and usually comorbid patient population, and it doesn't account for things like unexpected or unplanned visits for urinalyses for urinary tract infection, for example, or any of their other medical appointments, for things like cataracts or diabetes or any of their comorbidities.
It's really a lot that we're asking our older patients, and I think it's no surprise, then, that intravesical therapy is discontinued, maintenance intravesical therapy, I should say, is discontinued at rates much higher than would be expected based on adverse events alone. I think this idea really highlights the concept of time toxicity of cancer therapy, which is a patient-reported outcome metric that's been proposed by a medical oncologist at the University of Minnesota, where time toxicity is defined as the time a patient spends not only receiving their treatment, but also coordinating their care and driving back and forth or traveling from their home to the facility to receive their healthcare, because all of these things inhibit their ability to otherwise spend their time doing what they'd like to be doing.
You can see on this figure here from their manuscript, a hypothetical clinical trial, which I think highlights this concept fairly well. You can see, these are patients with advanced malignancy, and for option A, these groups opt for chemotherapy to prolong their life. As you can see, they have periodic visits for lab work, CT scans, actual infusions, and have an overall survival of 150 days, 90 of which they spent at their home not coming to the hospital. Now, compare that to option B, who are patients that didn't opt for the chemotherapy, and they spent most of their time at home with a short hospitalization for advanced symptoms right before they passed. These patients had a statistically significant lower overall survival, so 30 days lower, 120 versus 150 days, but actually spent more days at home, 115 compared to 90. I think it's not hard to see what type of patients that we see in our clinical practice may actually prefer option B, and that treatment path may be more in line with their treatment goals than option A.
As you mentioned, we have done some work to try to quantify this burden among bladder cancer patients. Last year we published a survey study we administered through the Bladder Cancer Advocacy Network's patient survey network for bladder cancer survivors, and we found a fairly significant burden. More than half of patients traveled more than 30 minutes one way from their house to their treating facility, so that's an hour of travel time alone, for more than half of the patients getting intravesicle therapy in the US, and a third paid more than $25 out of pocket for each visit, things like gasoline or parking fees. Over a six-week induction course, that adds up to over $150, which I think is not negligible for some of our older patients on fixed incomes.
On top of that, these questions, we also asked the question, "Would you be open to receiving intravesical therapy in your home as a potential strategy for reducing some of these burdens?" We were excited to see nearly three quarters of patients said yes, 72% reported openness to receiving in-home intravesical therapy. Based in part on these data, we have opened a phase 1B and phase two single arm clinical trial designed to assess the in-home delivery of intravesical therapy. We're currently in phase 1B with a planned accrual of 10 patients. We opened about three months ago and have accrued five so far, and this is accruing patients who are beginning induction intravesicle therapy with either BCG, gem/doce, gemcitabine, or mitomycin. We're asking them to receive the first dose of intravesical therapy in the brick and mortar clinic to make sure there's no problems with catheterization or tolerability of the agent, and then they move on to receive doses two through six in the home through a network of contracted home care providers.
Assuming no futility signals are met from the pilot experience, we'll then move on to phase two, which seeks to enroll 30 additional patients beginning both induction and maintenance therapy. The main difference being that maintenance patients, we will not require to get any doses in the clinic. They can get all their doses at home because they've already demonstrated ability to tolerate the agent. The co-primary outcomes of the trial are safety and feasibility, and feasibility we define according to the FDA's concept of adequate therapy. For induction patients, they need to get at least five of six doses of induction therapy within 12 weeks of enrollment, and for maintenance therapy, they need to get at least two of three doses within 12 weeks of enrollment, receiving all prescribed doses in the home, actually received at the home. If a patient reverts back to the clinic, that's a failure of the feasibility primary outcome.
Key secondary outcomes are patient preference and likelihood to recommend, and we're also assessing prospectively health-related quality of life, number of home days away from the brick and mortar clinic, unscheduled calls to the urology office, and three and 12 month recurrence free survival. The overall sample size of 40 patients between phase one and two arms provides 80% power to assess the null hypothesis that at least 50% of patients in whom we intend to treat in the home can actually receive all doses in the home, assuming 72% of patients are able to complete treatment as prescribed. In conclusion, we think that intravesical therapy is quite burdensome and that in-home treatment has the potential to reduce these treatment burdens, and we're really excited to generate some data to assess this approach.
Daniel Joyce: Wow, Tim, really fantastic work. Important work.
Timothy Lyon: Thank you.
Daniel Joyce: Really thoughtful approach to doing this. I love the outcomes you're looking at, specifically the health-related quality of life. You talk about staying at home, right? That's a big thing for patients, and when you look at that time toxicity chart from the JAMA paper, you can see, well, gosh, how much is overall survival really worth, right, if you're spending it in the hospital? A really important part of that is quality of life, because you can stay at home and your life can be miserable, and you can be in the hospital and life can be good. Understanding that component of it I think is going to be really helpful. Can you talk a little bit about what the logistics are to actually do this, what kind of resources you utilize to get this done in the home?
Timothy Lyon: Yeah, great question. We've got obviously a number of partners that help achieve this. We have our home care nursing partners who are trained in catheterization, chemotherapy delivery. As you know, any anti-cancer drug requires dual verification from two different nurses that you've got the correct patient and the correct medication. To do that in the home, we have an iPad-like device and get a secure connection, the same way you do if you're doing a video visit in your practice, to do the dual verification. For some of these medications, most notably BCG, there's a pretty limited shelf life. You may or may not know that the package insert for BCG says you only have two hours at room temperature after reconstitution, which, depending on how far you're traveling, can present a challenge. The way we've overcome that particular challenge is to use a closed system transfer device where in a sterile environment, we can attach the BCG vial to the saline, but not actually let them mix, so you keep the clamp on so they're not actually reconstituted, but it is put together in a sterile circuit. Then, that gives you essentially an indefinite transport time, and it's not actually reconstituted until you get into the home and the home nurse can open the stopcocks, let them mix, so that starts the two-hour clock, and then deliver it that way.
That's one of the challenges we've had to overcome.
Daniel Joyce: Yeah, wow. It raises a really important point, too, that as we get a lot of these newer intravesical treatments, perhaps the people developing these drugs, if this really becomes the way we do care, maybe they need to start thinking about the storage and how it's administered, and making sure that's feasible for patients. It could actually drive patient decision-making too, if that drug is-
Timothy Lyon: Oh, absolutely.
Daniel Joyce: If it's got to be given right away in the clinic, or is something that could travel. Are the people that are doing this, I assume they're the same people that give it in clinic, so they're experienced with it?
Timothy Lyon: No.
Daniel Joyce: You've hired new people that are traveling to patient's homes. Is that right?
Timothy Lyon: Correct. These are contracted nurses through a home care nursing agency based in Jacksonville, Florida, our city. They're not Mayo Clinic employees. They obviously have a relationship with us and we've done some training with them, but they're not Mayo employees.
Daniel Joyce: Is that something that if you looked at, and you may or may not be able to answer this, but from a kind of healthcare systems perspective, is it adding cost for you guys or is it saving cost for you guys because you don't have to use up that clinic space to put these treatments in?
Timothy Lyon: Yeah, it's an excellent question, and I think the jury's still out on that. I think we need to accrue more patients and get some more data before we can really meaningfully assess that, but I think that's an important point, right? For this to have legs, there needs to be reimbursement, but there's several layers to the financial assessment. You can look at apples to apples. Does it cost more money for the hospital to give it in the clinic versus giving it home? Then, you also need to think about, if you free up a brick and mortar clinic space, that opens up the opportunity for other revenue generating activities that may offset it to some degree. The other thing you think about is, if you're already sending a nurse at home, can you do other things that may be billable? Maybe they need a PSA check, maybe they need their cholesterol for their primary care.
I think there's lots of different ways this could go, and depending on what level of assessment you want to look at, a lot of different ways to view the financial impact as positive or negative.
Daniel Joyce: Yeah, I couldn't agree more. It's really, really exciting stuff. I think we're starting to get creative and see ways that maybe the future of healthcare could be done differently and be more patient-centered.
Timothy Lyon: Absolutely.
Daniel Joyce: I can't thank you enough. Really appreciate your time, and I look forward to seeing the results of this trial.
Timothy Lyon: Likewise, me very much as well. Appreciate the opportunity, Dan.