Study Shows Desire for Bladder-Sparing Treatments in High-Risk NMIBC

Joseph M. Jacob, MD

According to preliminary results from a study looking at reasons for refusal of or ineligibility for radical cystectomy among patients with Bacillus Calmette-Guérin (BCG)–unresponsive high-risk non-muscle invasive bladder cancer (NMIBC) who were enrolled in the TAR-200 (JNJ-63723283) monotherapy cohort of the SunRISe-1 study (NCT04640623), the most common reason for refusal was a preference for bladder preservation (52%), followed by concern about quality –of life (37%).¹

TAR-200 is a novel investigational targeted releasing system to deliver sustained local release of gemcitabine into the bladder. In December 2023, the FDA granted TAR-200 a breakthrough therapy designation for the treatment of patients with BCG-unresponsive high-risk NMIBC who are ineligible for radical cystectomy.²

Joseph M. Jacob, MD, looked at reasons for refusal or ineligibility for radical cystectomy among those with NMIBC enrolled in the TAR-200 monotherapy cohort of SunRISe-1. A total of 52 patients were treated and overall, 51 (94%) refused radical cystectomy.¹

According to Jacob, urological oncologist, Department of Urology, Upstate Medical University, Syracuse, New York, findings from this study supports further exploration of TAR-200 as a treatment option for this specific group of patients.

“The big takeaway would be that patients [who are] healthy and who would otherwise be fit for cystectomy are really choosing to try to seek out salvage approaches mainly for bladder preservation reasons and for quality-of-life reasons. I think that there is a strong need, a strong desire from patients for these treatments to be available and for us to develop these effective treatments,” explained Jacob, in an interview with Targeted Oncology^TM.

In the interview, Jacob discussed how bladder preservation is the top reason for refusal of radical cystectomy in the TAR-200 monotherapy cohort of the SunRISe-1 study.

Bladder Cancer, Urinary Bladder Image: © reineg - stock.adobe.com

Targeted Oncology: Can you discuss the rationale behind evaluating TAR-200 in the SunRISe-1 study?

Jacob: The SunRISe-1 study is investigating a novel drug delivery system in BCG-unresponsive patients. There is a strict FDA definition of [patients who are] BCG-unresponsive, and usually these are heavily pretreated patients. A lot of these patients have received good amounts of doses of BCG, and they are now determined to be unresponsive to BCG and so they need salvage options. In this particular space, there are not a lot of great options or there have not been in the past. It has been studied in the last few years. It is an exciting time.

In this particular SunRISe-1 study, it is a salvage therapy, and it is in the BCG-unresponsive patients. Now, what they are doing is they have a novel drug delivery system called the TAR-200. [It is] a silicone intravesical device that is placed with a catheter by a urologist or urology team. It is a slow sustained release of a constant dose of gemcitabine, which is a chemotherapy that many urologists are used to putting in the bladder. The difference is, instead of the gemcitabine being in the bladder for at most 1 to 2 hours, we think that this is giving a constant, effective intravesical dose of gemcitabine for at least about 7 days. It is a different way of treating these patients. We think that there is something important in the amount of time the tumor is exposed to intravesical chemotherapy. These patients are randomized, and we are only going to be talking about 1 of the arms, but the 1 arm that we will be discussing is the patients that received monotherapy with just the intravesical TAR-200 device.

Can you describe the typical patient that you encountered in this arm of the study?

These are patients that have received a good amount of BCG. They are heavily pretreated patients. Now, they are what we call BCG-unresponsive, which means that in these particular patients, we think that if we continue to give them BCG, it will probably be more harmful for them. These patients will probably progress on BCG. What we try to do is give them salvage therapies because we know that the more BCG we give these patients, the more chance that they can progress to more advanced disease. These are patients that are not going to benefit from BCG.

Classically, the standard of care has been offering radical cystectomy, which is a pretty big life change for the patient. It is a relatively morbid procedure. These patients that are enrolled in this trial are patients that are not wanting that option. They are mostly patients that are refusing cystectomy for various quality-of-life reasons. Very rarely, there is a patient that cannot tolerate a radical cystectomy, but most of these patients are patients that would rather try a salvage approach vs undergoing radical cystectomy.

Are there any key factors considered when making a decision about radical cystectomy? Were there any specific health conditions or comorbidities that played a significant role?

These are pretty healthy patients. Most of these patients could tolerate radical cystectomy, so it does not seem like there is a strong health- or medical-related issue that is pushing these patients. These patients are making decisions for quality-of-life reasons. From what we know so far, at least in this monotherapy arm, most of these patients are interested in bladder preservation. Their primary focus is preserving the bladder. Then, the second most common thing would be various other quality-of-life factors such as not wanting to deal with major surgery, but the majority of these patients are interested in organ preservation and bladder preservation.

How did the availability of TAR-200 monotherapy as an alternative to cystectomy impact patient willingness to participate in the study?

These patients are pretty motivated to do anything besides lose their bladder. So, if we tell them that there is another option out there, they are willing to listen. When [we] tell them the preliminary data, they get excited that it seems to be pretty effective in this patient population. The other thing that is pretty important is that it seems that urologists across the world are comfortable enough to offer salvage approaches. They are always counseling patients, and the way [we] counsel patients affects how patients make their decisions. It seems like patients are motivated to preserve their bladder and it seems like urologists are also motivated to use this sort of treatment approach. I think most urologists are comfortable, in this setting, to offer salvage approaches vs a radical cystectomy.

Are there any potential quality-of-life changes after cystectomy that influenced patient decision making?

Various factors, anything from recovery after a major surgery. There are 3 different options that patients have as far as what to do with their urinary diversion. I tell patients that they have to do something with the urine; the urine has to go somewhere. Some patients are trying to avoid an ostomy appliance, some kind of external appliance did not sit well with patients. Or even if patients get a neobladder, they have to deal with some sort of incontinence or temporary incontinence, and then these patients would have to catheterize themselves, so it is a huge life change as they do not urinate the same. Regardless of what [is done], patients are going to have to learn a different way of dealing with urine.

Overall, what are the key takeaways from this study?

The big takeaway would be that patients [who are] healthy and who would otherwise be fit for cystectomy are really choosing to try to seek out salvage approaches mainly for bladder preservation reasons and for quality-of-life reasons. I think that there is a strong need, a strong desire from patients for these treatments to be available and for us to develop these effective treatments.

Fortunately, what we are seeing so far is that the results are excellent, much better than we thought they were going to be. Almost 80% of patients are having a complete response at this point. This is preliminary data, but so far, most patients are successfully preserving their bladder. That is great. The key takeaway is, if we can give them another alternative salvage approach, I think patients are 100% on board with us.

What are the next steps for this research?

We have to see how [the data] plays out. We still need to gather more time, more data points. So far, we are dealing with a small group of patients. The study has accrued well, and it is almost done accruing, so we will have that data soon. Then, we just have to wait and make sure. Just as important as complete response rate, we want to know that this is also a durable treatment, meaning that patients, when they respond, tend to respond for a long period of time. We want to know how these patients are doing at 1 year, at 18 months, at 24 months, and so that is the next step. It is to show patients that this not only is an effective treatment, but it can be a long-term solution as well.

REFERENCES:

Jacob JM, F Guerrero-Ramos, E Xylinas, et al. Reasons for refusal of or ineligibility for radical cystectomy (RC) in patients (Pts) with bacillus Calmette-Guérin (BCG)–unresponsive high-risk non–muscle- nvasive bladder cancer (HR NMIBC) from the SunRISe-1 study. J Clin Oncol. 2023;42(4):701. doi:10.1200/JCO.2024.42.4_suppl.701

Johnson & Johnson’s investigational TAR-200 granted U.S. FDA breakthrough therapy designation for the treatment of high-risk non-muscle-invasive bladder cancer. News release. Johnson & Johnson. December 4, 2023. Accessed March 26, 2024. https://tinyurl.com/ydebn542