Dr. Bogdana Schmidt
Appearances
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
We'll be discussing highlights specifically in the bladder cancer field presented at ESMO 2024 in beautiful Barcelona. Before we get into it, I just want to point out how alive our field is right now. The meeting had over 5,000 abstracts submitted, over 600 invited speakers, but what I found fascinating was the statistics on the number of trials going on in GU right now.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Practical question again, just because I have the expert here. What about plasma cytoid, high volume plasma cytoid? Are you scanning those patients differently? Are you surveilling them any differently or about the same? Those are the patients that I always worry about. What if they're progressing on treatment? What if I'm missing a resectability window?
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Excellent. Well, thank you. Again, I think this is really interesting and promising data and certainly already has the potential to be practice changing as it is. And we'll just continue to learn more and more from it. Some of the questions that we'll be looking to learn from it will actually hit on discussing a few of the other studies.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So maybe we can move on to talking about your trial, talking about Ambassador.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
In my very young urologic oncology life, this is still incredibly impressive. There are currently 351 active trials in RCC, 188 in prostate cancer, and 929 in bladder cancer. This is unbelievable.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Absolutely. And like you said earlier, you know, we already had nivolumab approved before. So that's two positive trials in this space. We didn't really talk about Invigor, the earlier Atizo trial that didn't meet its primary endpoint, which could be related to the Atizo, could be related to where the trials were structured.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
But certainly, I think we have enough data now that adjuvant therapy in the post-cystectomy setting with nivolumab or pembrolizumab is here, right? So based on this, and obviously I know you have a little bias potentially because it's your data and you're familiar with it. So it's a good bias. If and when both drugs are approved and available in the clinic space, how will you choose between them?
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Yeah.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Is there any patient population or anything, just knowing, obviously, cross-trial comparisons are so fraught with so many problems, but is there any patient population for whom you might say, maybe nivolumab, we have slightly better data for? Or do you feel like the dosing schedule of Pembro kind of trumps things?
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Excellent. And I think you and all of our, I think, medical oncology colleagues have been using pembrolizumab for its numerous indications. So I think that the comfort level certainly is really interesting. Can you comment a little bit about upper tract disease?
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
We want something. We certainly all want something.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So now to just put a point on what you just made. So let's say you have a patient who refused cisplatin up front, not, you know, didn't get Niagara Protocol. Post-op, would you still be trying to engage in chemo or checkpoint if they're eligible but refused? Would you be trying to tackle that refusal for the second time or no?
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
From a cup now at the NIH, this may be less of a point for you guys, but let's say a patient refuses adjuvant chemo at this point. Are you able to offer them checkpoint inhibitor in lieu of it? Oh, yes, of course. Because I know that some folks will say that they can't get insurance approval for it if they're CIS eligible. But obviously, at the NIH, this is less of an issue.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And I know there are ways to get our patients what we think is in their best interest. But even with all of this immunotherapy data, When patients didn't get cisplatin up front, we're still sort of advocating for cisplatin adjuvately because that's what we have the strongest longitudinal data for. So I'm sure that space will continue to evolve. Now, you almost led me straight to the...
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
to the next topic, which is how are we going to figure out how not to over-treat these patients? Because you mentioned in Niagara, right, we're having patients get dervalumab up front, then chemo, then dervalumab. Now we have ambassador and checkpoint data for just adjuvant, but we also know there are probably
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Quite a few patients that are cured by surgery alone maybe don't need adjuvant or including that neoadjuvant space. So we're all talking about other markers. Is it imaging? Is it blood? Is it urine? We had the TOMBL trial presented.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
What do you think about that if you want to talk about TOMBL or you want to talk about what you're doing in practice and how you're trying to answer that question for your patients now? Yeah.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Absolutely. And I think that goal actually is reachable. You know, when I started even just a few years ago, I used to tell patients, look, if we're still doing the same thing in bladder cancer 10 years from now, we haven't done our jobs. And even in the last few years, we've made such interesting and promising advances that I'm really hopeful we'll get there.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Now, absolutely. And just to highlight a couple of details from Tambola. So you're absolutely right. Over 52% of their patients were CT DNA positive after cystectomy, which is a lot higher than you would think, at least certainly higher than I would have guessed.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And the wonderful thing is they were doing very serial kind of monthly measurements and 75% of patients were detected in less than four months. So you're thinking about adjuvant therapy. Generally, we start within three months, right, based on the trial. So
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Using ctDNA, we would have that window to pick those patients and still have time to start them on the treatment that we would start, but potentially select out the ones that maybe didn't need it. Now, I'm looking forward to the rest of their manuscript data to see how often do you actually need to be checking.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Correct. And that was 10%. So you said, you're right, for Tombola, it was 15%. Two patients, 3%, but in the Invigor, it was up to 10% of patients. But I kind of wonder if that has to do with the sensitivity of the assays. They were doing different assays in these studies.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So I wasn't sure the best way to organize this chat. So I think maybe we should start with the most advanced, most likely to be practice changing abstract, and then spend some time on things that are interesting and thought provoking, maybe not quite prime time.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So in your perfect scenario of this perfect biomarker that I truly am optimistic it'll come. It may not be perfect right away, but we'll have something where we have nothing right now. Do you use ctDNA in your practice right now to make decisions? I do. I do.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Yeah, I think so too. I think the medical oncologists I work with who are phenomenal and I love them and trust them very much, but they have the same struggles that you're experiencing. They actually don't wanna check because they don't know what to do with that information.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And I think the prospective data at InVigor and Modern, like you mentioned, are going to give us that data and hopefully help us figure out how to interpret this so that we have less hesitation to get the data in the first place so that we sort of know what to do with it.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So this gets me into my next question, which I wanted to ask after Niagara, and then I wanted to ask after Ambassador, and I figure I just have to ask it now. So the earlier and earlier in the system that we're introducing checkpoints, right? We hope, of course, that all of that works and our patients don't progress and don't develop metastatic disease.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And that's why we do all of it, which makes perfect sense. But now that we have really great EV PEMBRO data for metastatic disease, and I know you don't have a crystal ball to tell me for sure how using checkpoint up front will impact that data. But what do you think? Are you worried that it'll make that data look worse? Or do you hope that it'll make it look better because of a priming effect?
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
But I definitely want to get your thoughts on where you think the field is heading and what you'll be looking forward to in future meetings. So with that in mind, let's jump into the Niagara trial presented to Dr. Tom Powell's.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Thank you. And like I said, this is something that we're all going to ask more and more as we basically have more of these patients, right? Right now, these are all patients that have just been on trial. And so we'll be following them closely. But as we start to make these decisions, hopefully we'll get some more real world. evidence in this space.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So we've spoken about the more advanced bladder cancer setting, the muscle invasive, kind of how to make these decisions. I do want to talk a little bit, just for the surgeons in the audience, about some of the more surgical trials, the Sunrise trials, starting with Sunrise. four, which was the muscle invasive trial with citralumab and TAR200.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And I think this one points a really great point on what we mentioned earlier with the patients who refuse cisplatin. In this set of patients, there are just 60-something percent of patients that enrolled on this trial We're cisplatinum eligible, but refusing cisplatinum.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
I think speaking to investigator excitement potentially and wanting to get patients on trial, but also speaking to the fact that patients don't want cisplatinum. They want something newer, better, hopefully less toxic. And now that we have these newer agents, newer devices, delivery mechanisms, I think this is interesting to figure out how are we going to incorporate that into the paradigm.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Yeah, so just to quickly introduce Sunrise for kind of the concept. So this was the muscle invasive patients who were chemo ineligible or refusing, who got TAR200 plus citrelumab versus citrelumab monotherapy. And this was in that five to three randomization that maybe we can talk about a little bit. Those patients then went on to get radical cystectomy.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And because this was phase two, we were looking at pathologic complete response patients. as the primary endpoint in these patients. And it was really, you know, I think, striking. CR in that combo arm, TAR200 plus citralumab, was 42%, which is sort of what we saw in the neoadjuvant chemo trials. Nothing went above 30%, right? So there's some neoadjuvant immunotherapy trials, but
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
PathCR 42% with complete response. I think it's promising, very promising.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Absolutely. And then just getting to Sunrise One, which was obviously in the non-muscle invasive space, they also showed incredibly promising results, 83% with just TAR 200 alone, which I think is really great. I'm personally, as a surgeon, a big believer in TAR. intravesical treatments for intravesical-only non-muscle invasive disease.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
But looking at, there have been a couple combination trials now, right? So the Sunrise 1, looking initially with a citrelumab plus tar, and then you have data with creatostimogene in combination with PEMBRO. I think that, and then, of course, we had the PEMBRO data alone, which To me, that doesn't seem to be the primary direction that people are going.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And I think as a surgeon, we all want intravascular treatments for localized disease, one, because that's something we're comfortable with. But two, I think it more comes to the fact that we're comfortable managing those side effects, right? We know what to expect. We know kind of the worst case scenario for the patient.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And we know it's not going to necessarily be a hospital stay or, you know, stress dose steroids or anything kind of adverse immune. So as we develop more of these interesting mechanisms or delivery mechanisms, I think that we'll be able to offer our patients some new, better treatments than what we've had for them since the 70s.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
55%, which is, you're absolutely right. The durability is where it counts, right? That 83% number, that response at any point, that's great. We're all excited. But if at three months it looks great and at six months it's all back, then that wouldn't really help the patient. That just cost him a lot of money.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And you're right. We may see different data in longer-term follow-up. And once the noise, kind of the numbers of the patients that drop off, we might get a clearer signal with that. These are all still in the abstract phase. So we might learn more in that. But I still think it's exciting and promising. And so to get to exciting and promising, we've talked about periop immunotherapy.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
We've talked about biomarkers. We've talked about better intravesical intensification treatments. You've certainly mentioned, obviously, the big lofty goal of trying to decrease the number of bladders that we remove and making sure our patients live longer that way. What do you think is going to happen in the next six months to a year?
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
What do you think we're going to be talking about at the next ESMO or at the next GU-ASCO? Kind of what's in the pipeline that you're looking to hear about?
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Absolutely. Well, I think it's definitely an exciting time to be in the bladder cancer space, which is a wonderful thing for our patients and certainly an interesting thing for us. A lot to keep up with, but it's definitely promising. Well, I want to thank you for a wonderful discussion. This was so great.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
I think it's so nice to be able to hear the intricacies of these data and also figure out how it is that you're applying them in your practice already in real time. I look forward to... more conversations and hopefully more progress in the field.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Thank you so much. Thanks for having me.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So let's talk a little bit about the details of Niagara. So like you said, it's neoadjuvant cisplatin-based chemo with perioptervalumab addition. So these are patients who got dervalumab before and after.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
One of the things that I thought was interesting here, and I want to see what you think about that, as you mentioned on it about cisplatin versus carboplatin, is patients were able to receive cisplatin with a creatinine clearance of down to 40%. Is that your typical practice? Are you seeing patients going to split dose at 40, or do you generally cut off patients at 50?
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
One other thing I wanted to highlight for this trial, and maybe we'll come back to that as well, is the patient population here. So we looked at patients that were T2 to T4, N0 and N1. So there were some node positive patients here. And of course, in the comparator arm, patients were randomized to get just GEMSYS and radical cystectomy, didn't get any adjuvant treatment.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Looking at this trial, if you were designing it today, what would you have included or tried to do differently? Knowing, obviously, this trial was enrolling when I was a fellow, so five years ago, so I know we didn't have a ton of the data that we have now.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
But given the groupings, given the decisions that were made in the standard of care arms, if you were redesigning it, how would you do it differently now?
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Yes, which we'll get to in a minute.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
I agree. And I do want to get back to your point. I think that's a really important point of path CR as an outcome here, because that is tricky, right? We know that even from old trials, SWOG trial, Nordic, et cetera, that when we were looking at neoadjuvant chemo in this setting, there is a PT0 rate from TUR alone, meaning no neoadjuvant treatment whatsoever, in the 12% to 15% range.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And neoadjuvant chemo gets you 25% to 38%. There is that variability of did you get a good TUR? Was it in a location where you could have truly resected all of it? And those factors are really hard to account for. But I think to me, when I think about these things, I think that the distant metastatic potential is what I worry about the most. Right. That's why we're giving the neoadjuvant chemo.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
It's for the micrometastatic disease. It's to combat that. And so here the adjuvant stuff becomes really important because. PT zero, I don't know how meaningful of an endpoint it is long term. Right.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Hello, everyone, and welcome back to the Backtable podcast, your source for all things urology. You can find all previous episodes of our podcast on Apple Podcasts, Spotify, and at backtable.com. My name is Bogdana Schmidt, and it is my pleasure to introduce Dr. Andrea Apollo.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And I think to that point, so there were in this trial, correct me if I'm wrong, about 60 something patients, 63 patients who ended up not getting a cystectomy. So figuring out the data on those patients, I think also will be informative. What do you think about that and how that factors into how we interpret the data altogether? Yeah.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
If those patients remain disease-free, right? That's the important caveat because from retrospective data, we know that patients who were T0 after neoadjuvant therapy, who didn't go on to cystectomy, have a recurrence rate of up to 50%, right, if you follow them one to two years. And so obviously that's without adjuvant treatment.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
But I think that's where a lot of the future will come in is how can we treat this patient? How can we pursue Protect the bladder, certainly. I mean, if we get to a point in bladder cancer that I don't have to take out bladders, I won't cry. But I want my patients to do well.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And I think figuring out which patients are going to be able to do well with their bladders intact and how do we get them there, that'll really change the game. I mean, certainly that's what we all want. That's what I would want.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So anything else that you wanted to highlight on this? Because I think there's still quite a bit to talk about with Niagara.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
She's a tenured senior investigator, medical oncologist, and acting deputy chief of the Geomalignancies Branch and head of the Bladder Cancer Center at the NIH. She's led numerous GU clinical trials, including one we'll be discussing today. Dr. Apollo, welcome to the Backtable podcast. Thank you so much for having me. I really appreciate it. I'm really looking forward to this conversation.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Now, I agree with you. I think it's hard to ignore the data, and truly an overall survival benefit is incredibly meaningful, and it's what we've been wanting for these patients for a long time. A couple of practical questions I have in this space for you. So, obviously, there's still some nuance, but as this gets more broadly adapted,
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
adopted, what do you think we as surgeons need to be looking out for taking care of these patients perioperatively? I say this because that duralumab they're getting before, right, oftentimes managed by the medical oncology team. But in the acute post-op setting, we Generally, hopefully, you know, our patients do great, go home on day four and everything's smooth as butter.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
But knowing that they have gotten a perioperative checkpoint, do we need to be looking for other things post-op or in the acute periop period and not ignoring it, not thinking, oh, this is just nothing?
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
There were a couple patients who were pushed out for surgery, though. So they delayed time cystectomy. I don't know how that'll happen in the real world.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Yeah, I absolutely agree. I think to me, that's my main takeaway is if something doesn't look absolutely routine, my first phone calls to my medical oncologist and say, could this be immune related? What do I need to send? What other studies do you want me to get? And be thoughtful about that. With the amount of patients with variant histologies on this trial, it was up to 20%.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Are you seeing this as a positive, meaning you would extend this, basically this treatment paradigm to those patients up front, or do you want more data for that specific patient population?