Petros Grivas: Ashish, my friend, always a pleasure to discuss with you both in person. We were together last week in Brazil. Now, we're virtually. I'm very excited for bladder cancer data across conferences. As you mentioned, Ashish, AUA is coming up, I'm very excited, of course, for different datasets. And I will say, after seeing the data with EV pembrolizumab in the perioperative setting, Ashish, KEYNOTE-905 from ESMO and KEYNOTE-B15 on ASCO GU, I think there is significant attention to Pembro, EV in the localized perioperative muscle-invasive bladder cancer setting.
So I look at the AUA schedule, and I saw a number of presentations. For example, one open question, and I want your opinion, Ashish. I love your mindset and how you approach this. We have the question about patients who have oligometastatic disease. Let's say patients who get enfortumab plus pembrolizumab for metastatic disease, but maybe regional pelvic lymph nodes, maybe retroperitoneal lymph nodes. So these, they fall into the metastatic disease, not localized disease setting, and they fall under the EV-302 trial data with impressive overall survival and PFS benefit.
Now, if a patient has an extremely deep response, let's say complete response with EV pembrolizumab in that context, the question that sometimes comes up is, is there a role for consolidation, surgery or radiation of these, let's say, preexisting oligometastatic scenario? And we're always worried about other microscopic distal mets somewhere else.
But I think this question is open. And I saw in the AUA schedule, we have a session about EV and Pembro, Moving Earlier. That's the name of the session. And there is a discussion about consolidative surgery after induction of EV, Pembro, which I think will be interesting to see that. Have you seen that in practices, patients with oligo mets, great deep response, complete response? Does the question of consolidation come up?
Ashish Kamat: Petros, it absolutely always does. And you and I have put our heads together here in Houston at IBCG, and in Milan at [inaudible 00:02:56] and at all these different places. And really looking forward... I don't want to steal the thunder of what's going to be presented at AUA, but you're going to see, and I think that's a very important session.
The other one that we're going to tackle during that similar session is a crossfire, and an important question that patients ask, "Do I need to have my bladder taken out now that I have systemic disease?"
So one aspect is you have oligometastatic disease, should you consolidate either surgery or radiation? The other one is, should you consolidate at all or can you just observe these patients? So that's another thing that I think our audience really should be looking at.
If you had to look at the list, Petros, of all the presentations that are occurring or going to occur at AUA, do you think there are going to be any surprises, anything that you are expecting or may not have been expecting? I know it's hard to ask that question because you haven't seen it, but do you think there might be any surprises coming for the audience based on what you know of the field?
Petros Grivas: Great question, Ashish. It's hard to tell, to your point. I'm just looking at the program here. Another thing that I think will be interesting to me, and maybe a surprise is another discussion about the impact of prior checkpoint inhibitor in patients who are receiving EV, Pembro. So, the question is the checkpoint inhibitor is challenged question. And we had a manuscript published recently with Dr. Karine Tawagi and Dr. Ali Khaki and other colleagues looking at a survey, let's say, across oncologists in the country, in the US, asking them about the rechallenge with a checkpoint inhibitor. And many of them were not enthusiastic about rechallenging.
Having said that, it depends on multiple factors. For example, the timing of the last dose of checkpoint inhibitor and the time of recurrence. What was that treatment-free, progression-free interval? Prior toxicity or tolerability with checkpoint inhibition may be relevant in decision-making. I think it will be interesting to see that discussion at AUA.
And for context, I want to highlight the newly launched phase-3 trial that Monika Joshi at Penn State and MAIA are co-sharing. It's called, ECOG-ACRIN 8231. It's a phase-3 trial with pembrolizumab plus sacituzumab govitecan with growth factor support as primary prophylaxis versus conventional chemotherapy, platinum gemcitabine or taxane immunotherapy, depending on what prior therapy these patients had received. So, these are patients who have prior immunotherapy. So, we're asking the checkpoint inhibitor rechallenge question. Just launched, we have a few patients enrolled, and we'll see. Sacit, Pembro with growth factor primary prophylaxis versus chemotherapy. So, that session, I think it's interesting in that context.
I think the other interesting factor is a ctDNA discussion. And I know ctDNA is a major biomarker we're using in practice. We had discussions together with IBCG, and colleagues in Milan, Italy. So, the session is called, ctDNA as a Decision Tool. I think it's a very high-yield topic. Hot topic, I would definitely do not want to miss. The question is about the prognostic of ctDNA. I think it's pretty clear, but I think the nuances are still being discussed.
For example, if you give neoadjuvant treatment and you have ctDNA not cleared or potential going up, do you go for cystectomy? That was the initial plan. I think there is a topic, session discussing that particular question. And of course, what about other biomarkers beyond plasma ctDNA? How about urine DNA? I know you and me are watching that field, very promising data, but urine DNA need more data there. It's probably not ready for prime time. I will be interested to see that as well. And of course, how the dynamics, the kinetics of ctDNA look over time. I think that will be very interesting.
Another quick comment is, again, hard to predict surprises, but I know we have this debate forever between trimodal therapy versus radical cystectomy, and there have been multiple datasets, meta-analysis. We never had the chance of doing a randomized phase-3 trial comparing these two strategies. I know there is a meta-analysis at AUA. We'll see what that shows.
And again, the discussion about bladder preservation, it's a AUA, the audience and the participants are mainly French and colleagues in urology. So, the surprise would be if there is wider, let's say, discussion or acceptance of bladder preservation, which is, I think, an ongoing discussion. And the big question is the right patient in the right time. Who are the patients who can preserve the bladder and in which modality? And I always say bladder preservation, if it happens, it involves urology. Urologist is a big part of that strategy.
So, looking forward to the data, I think it will be an exciting meeting, and there will be a lot of discussion about other biomarkers. I know there is discussion about intravesical therapies. And of course, one of my favorite topics, histology subtypes, variant histologies in bladder cancer, a lot of discussion about different variants. Sarcomatoid, for example, there is some data suggesting resistance. We need prospective trials. And I think looking at these variant histologies in prospective trials will be very important. So, any data in that context will be helpful.
And again, of course, optimizing the duration of therapy, perioperative therapy, EV, Pembro, neoadjuvant, adjuvant, how long do you give? Do you follow the trial design? For now, yes, and you adjust patient toxicity. But can we refine our treatment duration? That's one of the ongoing themes and looking forward to data at AUA.
Ashish Kamat: Yeah, no, I think you summarized it really well, because a lot of the groundbreaking data presentations, of course, in the muscle-invasive and metastatic setting, leaving aside a non-invasive, the metastatic and muscle-invasive setting locally advanced occurs, of course, at general oncology meetings, ESMO, ASCO, GU ASCO. And at the AUA, I'm really looking forward to all the sessions. And Dave Penson's done a great job, and the whole committee, of actually teasing out these things just as you mentioned and these buckets, these sort of themes that are occurring that will help the urologist, and not just urologists, but uro-oncologists, urologists, medical oncologists that are in the community taking care of these patients, to distill down and understand some of these nuances in a very practical way.
And this is going to be at the plenary sessions, the podiums, the posters. And I'm sure, I don't know for a fact, but I'm pretty sure almost can guarantee Uro Today is going to have excellent coverage of all these things. So really looking forward to that. And of course, as you know, as part of the IBCG, we're going to have our bladder cancer forum and we're going to tackle some of these debates there, too. So, really, I appreciate you taking the time and going through the program, Petros, and highlighting everything. I just hope that people have enough time to run from different rooms because there's so much going to be going on.
Petros Grivas: Absolutely. I agree with you 100%. So, much going on. And I always am excited when I go to AUA, ASCO, ASCO GU, and other meetings to try to be in every room and sometimes there are conflicting schedules. But I think attending those sessions and also looking at the content, the slides later, I know there's a lot going on in the field. And you and me both know and discuss that it's completely different disease now compared to 10, 15 years ago. And this is because of the amazing ongoing research that is going on and also the applicability, the application of research to our patients.
And with International Bladder Cancer Group and the great work you are leading there, we try to expand the scope and the application of this amazing research across different countries and different worlds and the work you are leading, for example, with guidelines in different countries. It's exciting because the research we're seeing at AUA is fantastic. And then implementation science, as we call it, how to make that applicable and diverse across the globe. And that's an important next step. And I'm excited for that all happening, my friend, and all the collaborations together.
Ashish Kamat: Well, very kind words, but Petros couldn't do this without you. You're an integral part of the entire effort of the IBCG, and you and I are global citizens. And again, thank you for taking the time.
Petros Grivas: Thank you so much, and thanks to Uro Today as always.