Dr. Andrea Apolo
Appearances
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So patients with variant histology often are not included in trials. So I do love the fact that they did include patients with variant histology in this study. And I treat these patients as I would regular urothelial carcinoma, unless there's a small cell component in it or a neuroendocrine, a high-grade neuroendocrine component. Then I treat them as more like a lung component.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
small cell cancer with that kind of paradigm in terms of the systemic therapies that I use. But in general, patients with variant histologies, I treat them as urothelial carcinoma until we have prospective data showing that another regimen or something different would be better for these patients.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Those are the patients that I get super nervous about because although they do respond well to platinum-based chemotherapy, they respond well to checkpoint inhibitors. They do have a higher rate of positive margins. They have a higher rate of recurrence. And I don't know how to better manage them with the therapies that we have right now without prospectively testing them.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
But I feel like those patients... do need close surveillance and may benefit from more aggressive therapy, but I don't know what that more aggressive therapy is. I do think that they need systemic therapy. So I think going straight to surgery is not the answer.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
I think they need more systemic therapy probably than other patients, but how to intensify that systemic therapy, I think we need to learn that. We don't know yet.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Yeah, sure. So the Ambassador Study, I was really excited to present the 45-month follow-up for the Ambassador Study. We had presented the 22-month follow-up at GU-ASCO, and we had a lot more data now. We're really fortunate to do a concurrent publication in the New England Journal of Medicine with the outcomes of the Ambassador Study.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So just to kind of summarize what it is, this is a phase three study randomized for patients with muscle invasive urethelial carcinoma who undergo radical surgery and they have high risk disease. And by high risk disease, This means they received neoadjuvant cisplatinibase chemotherapy and have a persistent T2 muscle invasive disease or greater.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And this includes positive margins and positive lymph nodes, which, you know, it's kind of special that we included positive margins. Or they did not receive cisplatinibase neoadjuvant therapy but have a T3 or greater muscle invasive disease or positive lymph nodes or positive margins.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So those patients were randomized and this trial was designed a while ago where there was really no treatment for these patients in the adjuvant setting, especially if they couldn't receive cisplatin and base chemotherapy, either neoadjuvant or adjuvant setting. The patients were randomized to receive pembrolizumab for one year versus observation.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
with the dual primary endpoint of disease-free survival and overall survival. So we reported the outcomes of the disease-free survival and we found a doubling of the disease-free survival with adjuvant pembrolizumab. So it went from 14.2 months with observation to 29.6 months in the patients receiving pembrolizumab. So this was really exciting.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And the results just show that adjuvant pembrolizumab is effective in this setting and should be considered an option for patients that have high-risk muscle invasive disease.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So great question. I wanted to also mention that we did look at PD-L1 status because in the nivolumab 274, checkmate 274 study, it was actually the patients that were PD-L1 high did better. And although here in the United States, it's approved for all patients, regardless of PD-L1 status, in Europe, it's really only approved for patients that are PD-L1 high, the adjuvant nivolumab.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So we did look at the marker in our study, in the ambassador study, and we found that it didn't matter if you were PD-L1 positive or negative, both groups had a benefit. So I think that's important because you're not worried that you're treating somebody that's PD-L1 negative and they're not going to have a benefit.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
It was really strange actually that in the patients that were PD-L1 negative, they had the largest benefit, although there was a benefit in both groups. So regardless, the point is that we don't need PD-L1 status to select the patients for treatment for adjuvant pembrolizumab. And in terms of which one I would use, I was using nivolumab for a while.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And then while my trial was ongoing, I was using pembrolizumab. Then while we were waiting to date, I was using nivolumab. And now I've gone back to using pembrolizumab. And the reason I like pembrolizumab, I like them both, to be honest. They're both pretty easy to use. The nivolumab, the trial was done every two weeks. But I use them monthly because that's an FDA-approved dosing.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And for Ambassador, we did it every three weeks. But I use the six weeks. Every six, right?
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So it's kind of nice in the adjuvant setting to let the patients have time off coming to clinic and seeing them every six weeks in terms of dosing because that's an FDA approved dosing schedule for pembrolizumab. So I think that's a plus that you can give it every six weeks.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Yeah, this is this to me, it's like a dream come true. So we've always given patients platinum based chemotherapy for bladder cancer with really not that impressive results. But, you know, we've done a lot of trials and we really struggle to do better than platinum based chemotherapy. And now we're doing this in the metastatic setting and we're bringing it to the perioperative setting.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
I think there are more similarities and differences. And from the outcomes that we have seen, I don't really see any difference. So I use pembrolizumab. I like the dosing schedule, and I'm very comfortable with it.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So the upper tract data was not as robust as what we had seen in, you know, what we had hoped, but we had seen in lower tract patients, which are predominantly bladder, and it did include some urethra, but predominantly bladder. About 20% of the patients were upper tract, and we didn't limit the enrollment of upper tract.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And we actually didn't see a difference in terms of benefit with adjuvant pembrolizumab versus observation. And I can't explain why yet. We've done a bunch of subgroup analysis to try to tease out ureter versus renal pelvis. And the truth is these numbers are so small and the confidence intervals overlap. So it's really hard to make any conclusions from the data that we have.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
It is a different biology, but I would have thought that these patients... maybe perhaps would have had a great response. And right now, I think we have a lot to learn and we need to tease that data a little bit more and really do trials in upper track to better understand who are the patients that benefit. Now, that being said, given that the trial was not really designed to
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
select for the upper tract patients and you can't make conclusions from subgroup analysis, I give it to upper tract patients. But I tell them the data. I tell them the data and I say, do you want it? And most patients want it because they... Upper tract is scary.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
The question that I think comes up is what is the role now of adjuvant immunotherapy now that we have the Niagara data, right? So how does that fit in? I mean, if everyone's going to be getting Dervalium-AV plus Gem-Sys in the neoadjuvant setting,
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And the truth is that that's not going to be the case because there's a lot of patients that, you know, refuse cisplatinum-based chemotherapy, are not eligible for cisplatinum-based chemotherapy, are not going to get any neoadjuvant chemotherapy. About, you know, half of our patients in the ambassador study got no neoadjuvant chemotherapy.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And, you know, the predominant reason was because they weren't eligible to receive it. And then there's also a group of patients that we think are not T2. And then we do the surgery and they are. And they are really high risk, higher than T2. So I think for those patients, adjuvant checkpoint inhibitor is still an important treatment option.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So I think that's where we'll kind of fit with the Niagara data that we just saw.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
No, that's a great question. And right now what I'm doing is I do offer them cisplatinum-based chemotherapy if they did not receive it and they were eligible. But again, if they refuse it in the neoadjuvant setting, they're probably going to refuse it in the adjuvant setting.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
They have their fear of the platinum-based chemotherapy, which we try to alleviate, but a lot of patients just don't want it. But I do offer it to patients if they didn't receive it and they're eligible in the adjuvant setting, I do offer them cisplatinum-based chemotherapy. And I also offer it for upper tract patients, which, you know, we have protective data for that.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So I think it's a really exciting time where we can actually play around with the therapies that we have in terms of designing clinical trials and find the best treatment options for patients and hopefully in the future, spare their bladder and improve their overall survival, which is really the goal.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
It's such a great question. And I think there's a lot of effort right now ongoing to try to understand the role of biomarkers, specifically ctDNA, and how we can incorporate them prospectively and better select the patients that actually need therapy. So as medical oncologists, we intensify treatment a lot because we want to
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
provide the best overall outcomes for patients safely, of course, but give them the best chance. But we do over-treat patients. And I think that's why one of the reasons these adjuvant trials are so large is because we have to treat a lot of patients in order to see a benefit. And a lot of patients that we're treating, we're over-treating them, right? So not everybody needs it.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And then there's a small group of patients that may need even more that They may need intensification and just monotherapy, immunotherapy is not enough. So I think that's where the role of ctDNA comes in. And I love that there are prospective trials trying to answer that question right now, the Invigor 011.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
is trying to answer that question, treating with atezolizumab, using ctDNA to treat those patients. The modern study here in the US is also asking that question, using ctDNA to decide whether you intensify the treatment or whether you do you really need the treatment, and really only treating the patients that are ctDNA positive or that convert to ctDNA positive in a randomized fashion.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So I love that. And the Tembola trial did that in a non-randomized fashion using ctDNA and seeing if they can treat the patients that are ctDNA positive or convert to positive with adjuvant atezolizumab and seeing if those patients did better. And the nice thing is that they showed that One of the things that was really interesting, I thought that they showed was that high risk.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So so we categorize patients into high risk and low risk patients. Right. And yes, the high risk patients had CT DNA, but not all of them did. And then there were some patients that were not high risk, you know, by our criteria. And they about half of them still had positive CT DNA. So, you know, we think we're good using clinical baseline characteristics in terms of how to make patient how to.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
how to stratify patients into the highest risk. But we may not be capturing all the patients that are actually high risk and do need treatment in the adjuvant setting. So I really like that part of the Tembola trial and then following them and seeing they convert you know, how many of them converted with treatment, and then how did they do with the tezolizumab treatment.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So I think that this is a really important study, and more studies are going to be done that are actually randomized. So this kind of set the stage, and we have retrospective data also. So I think this kind of sets the stage for the importance of ctDNA within this perioperative study, and then what to do if you do have a positive ctDNA response. how to follow the patients, kind of what to expect.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
I mean, this is all evolving right now as we speak. So I think it's really exciting to have a biomarker to work with.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
I'm actually excited about the TAR system. The TAR 200 is with gemcitabine, but I'm excited about the whole device and the way that you can deliver it into the bladder so easily. And it delivers a slow amount of drug into the bladder. I love that. And the possibility that you can put other drugs.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
That's a little much. We decreased that. And I liked how sensitive it was, really, of the ctDNA negative patients. Only two of the patients developed metastases. Now, of course, my hope would be that it would be zero and that it would be super sensitive and it would pick that up. And we saw that also.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
In the early data presented from the InVigor 011, where they followed patients that were ctDNA negative, and they did see that some patients, although a really small percentage of patients that were ctDNA negative, did have progressive disease that was metastatic, that was not picked up.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
They were, and I think that we're only getting better. So we're only getting better. The assays are getting more sensitive. They're including methylation. They're even doing whole genome sequencing instead of whole exome sequencing now. So I think the biomarker is evolving, and we're only going to get more sensitive.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
active therapies in there so i'm really excited about it and i think we do need something that kind of manages the bladder right so we have these great systemic therapies but although most patients when they're responding to systemic therapies also respond within the bladder it'd be nice to have an additional intensification of treatment in the bladder potentially in the future to have bladder sparing approaches and this may be a way of doing it intensifying
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And sometimes I struggle when I don't see anything and the patient has already undergone all the treatments. So they've already undergone neoadjuvant chemotherapy, undergone radical surgery, undergone adjuvant checkpoint, and their NAD, and then they have this positive ctDNA. I don't know what to do at that point. Do I start more systemic therapy? How do I intensify the treatment?
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Do I restart checkpoint inhibitor? I mean, I think there's a lot of unanswered questions. The marker is available for us here in the US. And I think we need to learn how to use that tool a little bit better than what we know now. But I think it'll come.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And that would be the right thing to do, but it's hard for me not to check because I know that it's an available tool. And of course I want as much data as possible to make an informed decision for patients. But in some scenarios, we don't have the right answers to what to do with that result.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
I don't know the answer to that, but I do tell you that initially I was, when a patient got checkpoint and they develop metastatic disease, I was moving on to EV alone, but The more I thought about it and the more I discussed it with patients, I think that there's a synergy with EV plus Pembro and I think that it's reasonable to try to intensify the treatment that they're receiving.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So even if they progressed on checkpoint, continuing checkpoint and giving the infortimavidotin with pembrolizumab in the metastatic setting. So I am doing that. I don't think it's wrong just to give EV by itself, but I don't know what the right
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And whether we continue the checkpoint inhibitor or not, there is data in kidney cancer where there is no benefit to continuing a checkpoint inhibitor once a patient has progressed on it. But most of it has been done in the metastatic setting, although the most recent data with Tivolumab was done a little bit earlier.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
It did have some patients that had received adjuvant therapy, but a small number. And they did not see a benefit to continuing checkpoints. So I think this is an unanswered question. All cancers behave differently, have a different biology. We know that bladder cancer is not kidney cancer. So I think we need to answer this question prospectively.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And for now, if the patient can tolerate it, I do continue the checkpoint if they develop metastatic disease with and for Tamavidotin.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Yeah, so I was so excited to see the results of this study, especially after last year, we saw the really exciting results of EV plus PEMBRO in the metastatic setting. And then we saw the Checkmate 901 data, where when nivolumab was added to GEMSYS, it did better than just GEMSYS alone. And that just kind of set the stage for the perioperative trials that are
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Yeah, I'm actually excited about the TAR system. The TAR 200 is with gemcitabine. But I'm excited about the whole device and the way that you can deliver it into the bladder so easily. And it delivers a slow amount of drug into the bladder. I love that. And the possibility that you can put other active therapies in there. So I'm really excited about it. And I think we do need...
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
something that kind of manages the bladder, right? So we have these great systemic therapies, but although most patients when they're responding to systemic therapies also respond within the bladder, it'd be nice to have an additional intensification of treatment in the bladder potentially in the future to have bladder sparing approaches.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And this may be a way of doing it, intensifying treatment with these tar systems and then leaving the bladder intact potentially.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Yeah, and I'm glad that it was randomized because, you know, someone can argue, well, they received a systemic treatment with a checkpoint. But they did have a monotherapy checkpoint arm, and the pathologic response rate was much lower. That's right. Sorry, I could have said that, but it was 23%, so half. So it's nice to see that putting the TAR200 in the bladder intensified that.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
the treatment effect with almost doubling of the pathologic complete response rate. So I think I'm very excited about this data. And I think that it could be something we could potentially use in the future, along with all these systemic therapies that we are now developing in the perioperative setting.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
ongoing right now, and Niagara was the first one to report its outcome. And, you know, once I saw that the Checkmate 901 study was positive, that adding nivolumab actually did improve outcomes to platinum-based chemotherapy, but to cisplatinum-based chemotherapy, it didn't have as strong effect with carboplatinum. So that was...
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Yeah, and I don't understand part of the trial. I was very excited by the results. I think that it's great that there was such a great 12-month complete response rate. I think this is the best one that we have seen.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
But I don't understand why the combination didn't do as well as them or the monotherapy was the one that did the best, right? So that I wasn't sure if there was some antagonism or it was just the patients. These are really small numbers, right? I mean, the combination- I think it was like 50 patients versus 85 patients in the combination arm. So these are small numbers.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
But, you know, why is it that the monotherapy did so well in terms of the CR rate? I think it's the endpoint that is being measured. You know, if you're measuring a local endpoint. and you're giving a local therapy, the local therapy is going to shine. But why didn't it shine when it was in combination with the checkpoint?
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So I don't know if this is just a little bit of noise from the... I think they were very similar in terms of the 12-month CR rate, but I would have thought that it would have been a little bit better with the combination, and it wasn't. The TAR-200 did just as well as monotherapy in terms of the 12-month CR.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So I'm excited about the antibody drug conjugates in combination with checkpoint inhibitor trials. There's three large trials, and this is, of course, because of the amazing 302 data where we saw doubling of the overall survival in patients in the first-line treatment with metastatic bladder cancer.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And there are several trials that are ongoing right now asking that question in the perioperative setting. And similar to what we saw with the cisplatinum plus checkpoint inhibitor trials, they have a neoadjuvant component and an adjuvant component.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So there's the EV304 study for patients that are cisplatinum eligible where they get EV plus PEMBRO and in the neoadjuvant setting, and then they get it in the adjuvant setting, and then there's the control arm study. that just get neoadjuvant cisplatinum-based chemotherapy and nothing in the adjuvant setting. And then we saw a little bit of data from the Volga study at ESMO.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
important because we give cis-platinum-based chemotherapy for patients with muscle-invasive disease in the perioperative setting, neoadjuvant and adjuvant. So that's why I was really excited to hear the results of the Niagara. And of course, we had the press release that it was positive. So really excited to see the results of that trial.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And this was basically the safety run-in with the triplet EV, DERVA, TREMI in the neoadjuvant setting and then in the adjuvant setting. And they were really looking at clearance of ctDNA. And they found that There's a pathologic complete response rate, and there's also downstaging of the tumor, and there's clearance of the ctDNA. So that may be a good biomarker for efficacy. So more to come.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
It was really small. It was like 17 patients in the lead-in. But I think exciting in that, you know, the trial is... going forward. And there's multiple arms to that study. So they only showed the safety of the triplet. There's also a doublet with EV plus Dervalumab and then Dervalumab as adjuvant. And then the weird part is that the control arm is no therapy.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
But in all fairness, that's kind of what we did with our patients if they were not cisplatinum eligible. We didn't give them cisplatinum-based therapy because they can't receive it. We don't give them carboplatinum. And then we observed them in the adjuvant setting. So that's the control arm for the Volga study.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And then there's another trial also for patients that are cisplatinum ineligible, the EV303 study. And that one is EV plus PEMBRO again in the neoadjuvant setting and then in the adjuvant setting. And this is the great thing about EV plus PEMBRO is that it doesn't matter whether you are cisplatinum eligible or not. You can get this treatment. So they're, again, sandwiching it.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And they also have a monotherapy PEMBRO arm. And then they have a no therapy arm where they get no therapy in the neoadjuvant and no therapy in the adjuvant setting. So I'm excited about these trials.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
I think that, you know, if we see this fantastic activity that we saw in the metastatic setting, now in the perioperative setting with no concerns about surgical outcomes, then I think this will be the new standard of care. So those are the trials that I am really waiting to hear about. the results of over the next few years.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
This was great. You asked such great questions that are really important and that we're dealing with on a daily basis. And how do we now take this data that we just saw at ESMO and apply it to our clinic? And I think we're still figuring that out. So it's fun to have these conversations. And I think the conversations will be evolving. So more to come.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
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BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So great question. And that was one of the things that I really liked about this trial was that it was very practical and real world. And that's what I do in the real world is I go down to 40 and I split the dose. If I can make a patient cis-platinum eligible, I do. And whatever I can do to help the patient become platinum eligible is very important to me, cis-platinum eligible specifically.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So I will split the dose of cis-platinum and it's more tolerable. And that's what they did in this trial. And I really like that.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So great question. I think the standard of care has been the standard of care for a while until we had the approval of nivolumab in the adjuvant setting. And that just happened. It wasn't that long ago. 2021 was when that occurred. And I think that what I would have done differently had I known the activity of nivolumab and the activity of pembrolizumab.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
The ambassador study that I presented at ESMO and I presented the updated 45-month follow-up data. I would have done an adaptive design where if the patients had a pathologic complete response, then maybe we don't need the adjuvant approach. But the truth is we don't really know that, right? Because if we think about this as systemic disease, then maybe they do actually have
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
need a little bit more therapy in the adjuvant setting, even if they achieved a pathologic complete response. But I would have designed it more adaptively. And if the patients didn't respond, I don't think I would have continued adjuvant dervalumab because would there be I don't think there would be a good rationale to continue a therapy that didn't work in the neoadjuvant setting.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Now, that's not the way it was designed. Everybody got neoadjuvant in the treatment arm and everybody got adjuvant in the treatment arm. And in the control arm, nobody got adjuvant. But I think that it was a fair design without making it multi-arms. That would have been another way of doing it, but it's already a thousand patients.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So this would have made it a lot larger where we don't give adjuvant in a different arm. And it's not an adaptive design. It's just a different arm where patients do get adjuvant and then another arm where patients don't get adjuvant. So I think a lot to learn from this trial and we yet don't have
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
treatment with these tar systems and then leaving the bladder intact.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
The granularity of the data is if they did response, let's say they had a pathologic complete response, how did those patients do with adjuvant therapy versus if they didn't? How did they do with adjuvant therapy? How did they do in terms of event-free survival, which was the primary endpoint? So I think all these questions will be answered as the data is reported a little bit more and it matures.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
We've been using it as a surrogate for what's going on in the rest of the body. If you're downstaging, if you're responding in the bladder, which is something that we can observe and stage, although you can argue not as well as we think we can, at least that kind of gives us an idea of what's going on. And
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
And that's I think this study will actually help us to understand the role of pathologic complete response. And there's so many definitions of what actually is a complete response, a complete pathologic response. Do you count the carcinoma in situ? Do you count the low grade TAs? How rigid are you? Or is it just any non-muscle invasive diseases counted as a pathologic response?
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
I think that there's the definitions have been really variable. So it's been a hard endpoint to use. But I think we'll learn a lot from this trial.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
I think that'll be really important because that will be our ultimate goal. So those patients that failed because they didn't get a cystectomy, if it was by choice, then it's not really a failure. I think those patients should be followed. And I don't know if they got adjuvant therapy. I think it was mixed. Some of them did get adjuvant therapy, even though they did not undergo a cystectomy.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
But that may be the way that we treat patients. We treat them systemically with therapy and hopefully not remove their bladder. So in a way that failure is actually a success for patients.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Yeah, no, I completely agree. We need to learn from those patients. Yeah.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Well, just that I think time will tell in terms of the rest of the outcomes of that trial and their other trials. Also, that we're awaiting their data that include platinum-based, cisplatinum-based chemotherapy in combination with with a checkpoint inhibitor, including the Energize study with nivolumab. And we also have the Keynote 866 study with pembrolizumab.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So there are additional trials that had this similar approach where they gave neoadjuvant cisplatinase-based chemotherapy with a checkpoint, and then there was an adjuvant component. So I think reading, I think the outcome of those trials will be super important. But for now, I mean, I think that we have to consider this a new standard of care. I mean, patients did so well.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
They had an improvement in event-free survival, but they also had an improvement in overall survival. And that's so important for our patients because We've struggled to show an overall survival benefit in the perioperative setting. So we can be really critical about this trial, the way that they over-treated patients, but there was an overall survival benefit.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So I think, you know, we should consider including Dervalumab now in the neoadjuvant setting and in the adjuvant setting.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
I think we're learning. I think that's a great concern to have. In this study so far, they did not report any issues with surgical outcomes or even post-surgical outcomes.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
Yeah, and I think we need to understand that when the patients are getting combination therapy, the urologist and the medical oncologist need to stay really close in communications with labs because immune-related adverse events can occur at any time and often occur a little bit later. So could they occur postoperatively immediately? Of course they could.
BackTable Urology
Ep. 193 Bladder Cancer Innovations: ESMO 2024 Highlights with Dr. Andrea Apolo
So we don't have yet the details and the granularity of those kind of adverse events that occurred in this study, but I think that they will occur and it's important for the urologist and the medical oncologist to stay closely connected in this perioperative setting.