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Ashish Kamat: A warm welcome to all of you from the UroToday studios. I'm Ashish Kamat, Urologic Oncologist at MD Anderson Cancer Center. We are live here at ASCO GU 2025. It's my pleasure to be joined by Dr. Maria Jiang from Toronto. Welcome, Maria.

Di Maria Jiang: Thank you so much for having me. It's a great honor to be here.

Ashish Kamat: So you have a really interesting session at the podium, which is on ADCs in bladder cancer. And of course, ADCs are all the rage, not just because of the advances in metastatic disease, but also because of muscle invasive and non-muscle invasive disease. So share with us your insights a little bit on what you think the field is right now and where it's headed.

Di Maria Jiang: Yeah. Thank you. And it's a great honor to be able to discuss ADCs and bladder cancer. And it's an exciting session. And we have several speakers who are going to talk about different segments. But I hope to start with a broad overview.

ADCs obviously has triggered this sort of golden era in the treatment of bladder cancer. And it really has transformed our treatment landscape. I think it is going to be a very exciting time, especially as ADCs move into earlier stage disease like you mentioned, and probably will even have a broader impact in those settings where we likely will see more patients getting cured and hopefully enable more patients to have bladder-sparing approaches as well, which is still somewhat underutilized in muscle invasive bladder cancer. We see trials that are moving in the non-muscle invasive disease setting. So we'll highlight a little bit about that. And yeah, it's an exciting time.

Ashish Kamat: So obviously with all the advances that have occurred with EV pembro in the metastatic setting, I mean, clearly practice-changing and dramatic improvements, what is your sense as to where first-line therapy is headed, not just in North America, but for our international listeners?

Di Maria Jiang: Yeah. I mean, I think it really depends on access. And in North America and in Europe and in other countries, we have access to EV post-pembro. So I don't think we have figured out a subgroup of patients that don't respond to EV pembro as well as our traditional standard platinum chemotherapy.

So in a broad sense, in one fell swoop, EV pembro has really replaced platinum chemo. Certainly in other countries where EV pembro is not available, I think those patients are still being treated with platinum-based chemo and perhaps with maintenance immunotherapy afterwards. And a lot of those countries also don't have access to ADCs monotherapy afterwards. And I think a lot of efforts are still needed to advocate for equitable access globally to ensure those patients have proper treatment and the best treatments available.

Ashish Kamat: Great. Now moving into muscle invasive and neoadjuvant setting. We're obviously eagerly awaiting the results of the trials. What's your sense as to where that aspect is headed?

Di Maria Jiang: Yeah, thank you for this question. I'm really excited about muscle invasive bladder cancer. There's going to be an oral abstract session looking at the combination of disitamab vedotin plus toripalimab, which is a PD-1 inhibitor, in patients with HER2-positive muscle invasive bladder cancer. And this is using disitamab vedotin plus toripalimab in the perioperative setting for patients who are planned for radical cystectomy. And their reported PCR rate in the session from the abstract is 63%. And among patients with IHC 3+ tumors, it's actually greater than 80%, which is a very high bar.

We, of course, have seen single-agent EV in the neoadjuvant setting, PCR rates about 36%, and we recently saw in ESMO Asia with neoadjuvant sacituzumab govitecan with a little bit lower response rate. And I think a lot of these studies have the caveat of using PCR, which can vary in terms of their definition. So some studies are using PCR definition in the ITT patient population, while other studies are reporting only patients who undergo cystectomy. And of course, we know not everybody makes it to cystectomy. And some patients have a clinical response, and they refuse cystectomy, especially in the SG study.

But barring those sort of limitations with PCR, I think ADCs plus their combinations really have a significant potential to replace neoadjuvant chemo. And if that's the case, we're going to be able to eliminate cisplatin eligibility criteria, enable more patients to get systemic therapy, potentially getting more patients cured. And then we really need to think about bladder-sparing approaches a lot more now that our systemic therapy is getting better.

Ashish Kamat: Yeah, I'm glad you brought that up. And that's a very good point. I mean, we obviously take Pat-CR, and then we try to correlate with clinical complete response. And obviously, with our clinical staging the way it is today, we've refined that over the years, but we clearly have a long way to go before we can tell the patient that a CR is the same as a Pat-CR. And again, you brought up a good point that they're defined differently.

For the patients, though, it matters whether he or she individually has a Pat-CR. So I think that's where the whole ITT versus radical cystectomy patients alone makes a big difference. But the numbers are startling. When you have 60%, 70%, 80% Pat-CR rates. It behooves the question, did this patient need to lose their bladder. And we know that in the absence of treatment, at least with cisplatinum, the tumor comes back. But we don't know that with ADCs yet.

And that brings me now to, I guess, not the last part of our talk, but the last disease stage, which is non-muscle invasive disease. As we know, we have intravesical EV being used for BCG-unresponsive disease. What's your sense there as far as mechanism of action, patient population in the non-muscle invasive space?

Di Maria Jiang: Yeah, we really look forward to seeing this data. There's an area of unmet need there for patients with high-risk or very high-risk non-muscle invasive bladder cancer. I think the key questions here will also be what is going to be the optimal treatment duration for these patients, balancing the efficacy but also the toxicity of these treatments. The other question will be, how do we manage relapses if some of those patients do end up relapsing. But after moving ADCs earlier in the disease stage, how are we going to manage those recurrences after ADCs?

Right now, we don't have as much data. But certainly, in the non-muscle invasive setting, there are a number of options, and ADCs—especially like you mentioned, intravesical ADCs—is really promising.

Ashish Kamat: Yeah. Now you brought up the Pat-CR rate with HER2-positive, with 80% there. And if you have the [INAUDIBLE] micropapillary obviously is HER2-enriched. So I think we might be moving towards personalized ADCs. What's your thought there?

Di Maria Jiang: Yeah. And there are also other studies that are looking at non-urothelial histologies. And those early studies are coming. There are also ADC studies looking at upper tract disease. But I think ideally, if we had the resources, I think we should be doing not just histology, but multiplexed biomarker sequencing.

We have HER2 ADCs, we have nectin-4 targeting ADCs. SG approval has been recently withdrawn, but there are also other studies ongoing and other Trop-2 ADCs. But at different steps of the disease process, it would be great to understand what happens to target expression and what is the level of heterogeneity in the disease, and how do we think about sequencing some of these agents. And we do want to use our best treatments up front. But we need more data in understanding disease biology.

Ashish Kamat: That brings me to an important question that we often get asked by people. It's like, OK, if we have EV pembro for the metastatic setting, and we're in the non-muscle invasive setting with the Niagara data—let's assume the EV pembro data comes back positive. Would you say let's save EV pembro for if and when a patient becomes metastatic? Or in the sequencing paradigm, you're like, let's give the best treatment right up front?

Di Maria Jiang: Yeah, this is a great question. And different people may have different thoughts. My personal bias is that we really should be aiming to cure patients with our best systemic therapy up front. If there is an ability to cure patients, I would advocate for using those treatments earlier on rather than waiting for patients to relapse and hoping that EV pembro—although it's going to have a high response rate—it still remains unclear how many of those patients can we actually cure.

And this is going to be updated in the rapid oral abstract session tomorrow by Dr. Powles. But we know about 30% of patients have CRs, and those are durable responses. But we still don't know if those patients are going to end up getting cured. But we have an opportunity, if patients are in an earlier disease setting where we're able to get rid of micrometastatic disease and maybe consolidate it with some local therapy, hoping that those patients will not have their cancer come back.

Ashish Kamat: Right. Maria, I've really enjoyed our discussion. Any closing thoughts for our audience?

Di Maria Jiang: I just want to encourage clinicians to adopt the use of ADCs if it's available. I know there's still regions where this is a new treatment for physicians and patients, and there are toxicities that we need to identify early and manage appropriately. And I think if you are starting to use ADCs, sometimes there is a little bit of unfamiliarity. Certainly getting connected with a multidisciplinary team and other physicians who have been experiencing using this is a great start. And really trying to bring this option to our patients in a real-world setting will be really critical to really improve patient outcomes.

Ashish Kamat: Yeah, great points. And thank you once again for taking the time.

Di Maria Jiang: Thank you for having me.