Sandip Prasad, MD, on UGN-102’s potential as a non-surgical option in NMIBC

In this interview, Sandip M. Prasad, MD, discusses the study “Primary chemoablation of recurrent low-grade intermediate-risk non-muscle-invasive bladder cancer with UGN-102: A single-arm, open-label, phase 3 trial (ENVISION; NCT05243550),”¹ which was presented at the Society of Urologic Oncology 25th Annual Meeting in Dallas, Texas. Prasad is a physician at Morristown Medical Center in Atlantic Health System and Garden State Urology in New Jersey.

Sandip M. Prasad, MD

This transcript was AI generated and edited by human editors for clarity.

Could you describe the background and the design of the ENVISION trial?

ENVISION is the third study investigating a novel agent called UGN-102 (mitomycin). UGN-102 is a new paradigm in treating bladder cancer; specifically, low-grade, intermediate-risk, non–muscle invasive bladder cancer. These are low-grade tumors that generally recur frequently, that are large or multifocal. For urologists, these are the types of tumors that recur rapidly, recur frequently, put patients through a number of procedures, and generally carry a significant morbidity because of their repetitive nature. The idea of UGN-102 is to use a topical, non-surgical approach to treating bladder tumors, which is completely different than what we’ve done over time. Historically, we've always resected or fulgurated these tumors. In general, we've never had a non-surgical option to manage tumors primarily.

ENVISION was the third study investigating UGN-102 as primary treatment for low-grade, intermediate-risk, non–muscle invasive bladder cancer. The first study was OPTIMA (NCT03558503). It was a phase 2b study. The second was ATLAS (NCT04688931). It was a phase 3 randomized controlled trial between UGN-102 and [transurethral resection of the bladder tumor] (TURBT), the standard of care. ENVISION was the third study, and the one that is preceding the application for FDA approval.

ENVISION is a single-arm study; all patients received UGN-102. The medication is given intravesically, so similar to the way in which we administer most of our treatments for bladder cancer via a simple urethral catheter. Patients who had a tumor present that was recurrent—meaning they had had a tumor within the past year and that was low grade and characterized as intermediate-risk disease—were given UGN-102 via catheter once a week for 6 weeks. Then we followed up with the cystoscopy to assess for treatment response. Again, [this is] a single-arm, phase 3 study [with] 240 participants. All the participants received the study drug and then were evaluated initially for complete response following treatment. For those patients who were complete responders, they were followed for a minimum of 12 months to assess the durability of response. Remember, these patients are all patients who had previously recurred within a year; [we] follow them up for a full year and see how those patients that were complete responders did.

What were the key findings that were presented at SUO?

At the SUO we presented both the complete response rate and, for the first time, the 12-month durability of response rate. Again, every patient received the study drug once a week for 6 weeks, and these patients were assessed with cystoscopy, biopsy for cause, [and] urinary cytology. What we found was that 79.2% of patients were complete responders. So, almost 4 out of 5 patients who had no TURBT, had a tumor left in the bladder, [and were] treated with a topical instillation of UGN-102, when we look back 3 months later, had no tumor that was visible. That was the first and key finding was the 3-month complete response rate.

For those patients who were complete responders, we then followed those patients for 12 months. Patients had cystoscopies every 3 months, and then we assessed the durability of response by Kaplan-Meier analysis at 12 months. That's a standard approach for assessing durability of response for these types of studies. What we found is that [per] Kaplan-Meier estimate, for patients who achieved a complete response at 3 months, [there] was a likelihood of remaining in complete response of 82.3% at 12 months. The durability response for these patients was impressive given the fact that these patients were those who, by definition and by inclusion criteria, were recurrent within a year at [baseline]. Again, taking a highly recurrent patient population and treating them, almost 80% of patients [achieved] a complete response and then [there was] an estimated durability of response of over 80%. I think the study investigators are really pleased to find that this appeared to be a viable alternative to TURBT.

Importantly, the investigators felt that these were really efficacious numbers, both in terms of complete response rate and durability of response rate that most of us in clinical practice would [find] meaningful. The second component, of course, is safety. We looked to see what the treatment-related adverse events were in the study to make sure this was a safe and appropriate treatment to administer to patients. Overall, the rates of adverse events were very low. There were only 2 out of 240 patients that had a treatment-related adverse event. One was urinary retention; the other was urethral stenosis. These are both things that urologists frequently see and are able to manage, and both of these were actually self-resolved. So, we found that the safety profile also met what the investigators felt was appropriate.

What are the next steps for UGN-102?

UroGen, the company that sponsors UGN-102 has submitted the drug for FDA application. I imagine that that application will be assessed sometime in either Q2 or Q3 of 2025. For urologists looking for potential non-surgical alternatives for TURBT in a patient population that is fairly recurrent with low-grade disease, I hope that we'll be hearing news about the future of UGN-102 in a positive way sometime in the next 6 to 12 months.

Taking these findings together, what is the key take-home message for urologists?

As urologists, we're always looking for additional tools to help us with recurrence in bladder cancer. It's the critical issue, especially in low-grade patients, where tumors rarely metastasize and invade, but they frequently recur. These are not necessarily fatal tumors, but they're ones that cause significant morbidity to patients. The average age for a bladder cancer patient is 75. [For] many of our patients, the risk factor they had was smoking, and therefore many also have concomitant cardiopulmonary disease. Taking these patients to the operating room repetitively often involves risk for these patients that have baseline health issues. Many of my patients who have low-grade, intermediate-risk disease are on blood thinners, also because of their cardiac issues. For these patients, we have to take them off their blood thinners to do a TURBT, [which] puts them at risk for issues like heart attack and stroke, and then we have to re-engage blood thinners after resection, which can lead to issues like bleeding down the road, readmissions, catheters, etc. Again, although the disease is not so aggressive that it requires removing the bladder or any significant treatments, the reality of recurrent and repetitive TURBT has been shown to be harmful to patients and increases their overall mortality over time by just simple discontinuation of blood thinners. I think as urologists, we should all welcome a new tool to be able to use in patients that is non-operative.

Urologists will determine where this fits in the best. Is this a frontline treatment that may replace TURBT? Is this to use alongside TURBT in certain patients—older patients, more frail patients, patients on blood thinners, perhaps patients with multiple lesions that recur frequently, where, historically, our TURBTs haven't worked out well? Or is this something that urologists keep in their back pocket to know is available in those particular patients where they don't want to address them with TURBT? I think any additional non-surgical tool for anything we do is extremely advantageous, so I would encourage urologists to learn more about the drug. We'll wait to see if the drug is approved and if approved, I think there's a really nice opportunity to potentially change the way in which we manage bladder cancer, which is an incredibly exciting opportunity to change disease management in an essentially fundamental way.

Could you expand on how you foresee this agent changing the treatment paradigm if it were to be approved?

The traditional management for low-grade, intermediate-risk, non–muscle invasive bladder cancer is TURBT. There are some patients who have small lesions, and these can often be fulgurated, but these are typically low-risk, low-grade patients, [with] small lesions, single lesions. When we begin to talk about multifocal lesions, larger lesions, and patients who recur, we often find that fulguration is not the easiest way to address these types of patients.

We found that [there were] about 2% of patients in the study that investigators felt could be managed with fulguration. So, that was always our non-TURBT option for patients where we didn't want to take them to the operating room. We've discussed a little bit about what some of those risk factors may be: being on a blood thinner, being older, being more frail, and having issues and risks that are associated with general anesthesia. I think urologists are going to find those types of patients first. Those may have been patients where they were addressing them with fulguration even though that may not have been a really great option, but it was the best option that was available to avoid anesthesia. Now we have a completely non-surgical option, potentially, to be able to address those patients. I think that's going to be the first place that almost all urologists will begin to adopt this agent.

But I think that the other way to look at it is that we have a non-surgical option that works in over 79% of patients and is durable. The estimated durability is over 80% in patients. Those are very high numbers to me. I think there will be some urologists who will say this should basically be the first-line therapy, and we should administer UGN-102 to all patients who have bladder cancer that is low-grade and intermediate-risk. Then for those 1 out of 5 patients that are not complete responders, to then address those patients with TURBT. It's possible that as we go over time, this may completely flip the order in which we do things. Currently, it's always TURBT first, maybe wash the bladder with chemotherapy or something else afterwards to see if we can prevent recurrence. We may completely flip that on its head, where we're using these types of gel instilled chemotherapeutic options like UGN-102 first, and then use TURBT if needed in that small subset of patients that may not be complete responders.

Is there anything else you’d like to add?

We're trying our best to be able to share these novel findings with our urologic community. We're very grateful to the SUO for the opportunity to present these data in the fall. We have 2 abstracts accepted at [the Genitourinary Cancers Symposium], which will be in February. We'll be able to present those to our broader urologic community that includes our radiation oncologists and medical oncologists, as well as our urologic oncologists who attend that meeting. Then we'll be submitting additional abstracts for the [American Urological Association] to again approach our general urologic community, because these types of tumors, low-grade tumors, intermediate, recurrent, large, and multifocal tumors, are taken care of by every single urologist. This is not something that just affects a subset or a fellowship-trained component of urologic surgeons. This is something that every single urologist takes care of and manages. It's important for us to do our part to share these new and exciting data with the entire urologic community.

Reference

1. Prasad SM, Shishkov D, Mihaylov NV, et al. Primary chemoablation of recurrent low-grade intermediate-risk non-muscle-invasive bladder cancer with UGN-102: A single-arm, open-label, phase 3 trial (ENVISION). Presented at: Society of Urologic Oncology 25th Annual Meeting. December 4-6, 2024. Dallas, Texas. Abstract 121. Accessed December 10, 2024. https://suo-abstracts.secure-platform.com/a/gallery/rounds/21/details/3652