Webinar | Understanding A New Treatment Option for Advanced Bladder Cancer

August 28, 2025

EV + pembrolizumab is changing the way doctors treat advanced bladder cancer. In this webinar, Dr. Vadim S. Koshkin, MD, Genitourinary Oncologist at the University of California San Francisco, will explain how EV + pembrolizumab works, who it may benefit, and what patients can expect. You’ll also hear directly from a patient who has received this therapy, sharing their real-world experiences and insights.

Year: 2025

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Full Transcript of Webinar | Understanding A New Treatment Option for Advanced Bladder Cancer

Patricia Rios:

I want to welcome you once again to the Bladder Cancer Advocacy Network Patient Insight Webinar Series. My name is Patricia Rios, and I am your host for today’s program on understanding a new treatment option for advanced bladder cancer.

A combination treatment that includes EV plus pembrolizumab is changing the way advanced bladder cancer is treated today. This powerful combination is designed to help the body target and fight cancer cells more effectively. By doing so, it is offering new hope to patients and families.

To help us understand what is EV plus pembrolizumab, how it works, who it may benefit, and what patients can expect, we have invited Dr. Vadim Koshkin, genitourinary oncologist at the University of California San Francisco, where he co-leads the bladder cancer clinical program.

Dr. Koshkin received his medical degree from the University of Chicago Pritzker School of Medicine and completed his oncology fellowship at the Cleveland Clinic. His research interest at UCSF focuses on clinical trials, targeted agents, and biomarkers in bladder cancer. Clinically, he focuses on taking care of patients with advanced bladder cancer.

Joining Dr. Koshkin is his patient Robert Ashton, who will share his real-world experiences and insights with this therapy. Mr. Ashton resides in the San Francisco Bay Area, but is originally from Nashville, Tennessee. He has over 30 years of experience in healthcare and is currently consulting part-time to pharmaceutical biotech companies. Mr. Ashton sees each day as an opportunity to learn more about living with bladder cancer and in his free time, he enjoys traveling, cooking, hiking, music, and spending time with family and friends.

We’ll get to hear more from Robert after Dr. Koshkin’s presentation. But without further ado, I’m going to hand over the screen now to Dr. Koshkin for today’s webinar on understanding a new treatment option for advanced bladder cancer.

Dr. Vadim Koshkin:

Thank you, Patricia, for the very nice introduction. I really appreciate the … Well, BCAN putting on this event and the opportunity to really you know, share what I think is really very important data and very important information about this new treatment regimen that we have for, for patients with advanced bladder cancer.

Of course, in addition to me speaking about this today, one of my patients, Mr. Ashton, will join us as well and discuss the patient perspective here, which I think is, is really especially, especially critical.

Dr. Vadim Koshkin:

So the treatment we’re talking about, of course, is enfortumab vedotin and pembrolizumab. We will focus on what is this treatment and how does it work in bladder cancer. Of course this treatment combination consists of two very different drugs, right, and they’re drugs that work quite differently as well. So one is enfortumab vedotin, which I’ll discuss first.

Dr. Vadim Koshkin:

So this is a type of drug called an antibody drug conjugate, which is a new and a very different class of drugs than what we’ve had historically for bladder cancer and historically for cancers. It is really only over the last several years that we’ve seen these drugs sort of gradually become introduced into clinical practice across many different cancers. And in bladder cancer, this drug in particular was approved initially in about 2019.

Now there are several of these drugs approved across the oncology landscape, so not just in bladder cancer but for the treatment of other tumors, and they’ve been really, I would say, nothing short of revolutionary in, treating patients with cancer and in oncology. Then bladder cancer in particular, this drug, I would say, has been absolutely transformative as well.

So what is new and different about these drugs? Well, we conventionally used to give you know, chemotherapy by just infusing the chemotherapy drug into the patient’s vein, and then where it goes all over the body, and affects, of course, cancer cells, hopefully, and hopefully destroys them, but it can affect other normal cells and normal organs as well. That accounts for a lot of the toxicity, a lot of the side effects associated with chemotherapy and, as a result, can limit both the how much a patient can tolerate a given treatment and also really how effective it can be.

Well, these drugs, antibody drug conjugates, allow for a targeted delivery of chemotherapy specifically to the cancer cell. So these are complex drugs. They consist of at least three major components, as shown in the screen here. So an antibody, which is a protein that targets another protein. It usually is specific for another protein on the surface of cancer cells in the way that a key is specific to a lock. So it fits directly in and fits only you know for that lock.

And so, this drug consists of an antibody that targets nectin-4, a protein that’s expressed in urothelial cancer cells, and it is linked via a linker molecule to a chemotherapy drug. In this case it’s a chemotherapy drug called MMAE. There are different types of chemotherapy drugs that work differently, but this particular chemotherapy drug, when it enters the cancer cell, it affects the ability of the cell to divide and eventually leads to its demise. That’s how it is able to you know destroy cancer cells and destroy tumors.

Again, attaching this chemotherapy to the antibody that fits specifically to a marker on the surface of the cancer cell is what’s really kinda transformative here, allows us to deliver you know chemotherapy specifically to the tumor in a more targeted way, and allows, at least in theory, for a much more effective treatment.

Now, of course, you know, in real life, and certainly in the human body, things don’t work quite as cleanly. Oftentimes this chemotherapy drug can still fall off the molecule and cause side effects elsewhere in the body. But in the majority of cases, it is delivered to the area where we want it to go.

Dr. Vadim Koshkin:

The other drug that’s part of this combination is pembrolizumab or also known as Keytruda. This is a very different type of medication, so it’s an immunotherapy drug approved for bladder cancer, but also for many other types of cancers. The late President Carter actually was treated with this for melanoma, a very different type of cancer, and you know lived for 10 years in a situation that you know previously was highly lethal. And so, this is a drug that’s effective for a number of cancers, but is also specifically approved in the treatment of bladder or urothelial cancers.

It works very differently not by attacking the cancer cell directly, but by activating the immune system, revving it up in a way, to then attack the cancer. That, we think, allows for often more durable responses to treatment, because in a way it trains your immune system. It conditions it to recognize tumors better and to really go after them more aggressively.

Dr. Vadim Koshkin:

What’s really, I would say, transformative about this combination of these two drugs, which, again, work very, very differently, is that they have true synergy. What I mean by synergy is that the combination of their individual components, or the combination of these two drugs, is greater than the sum of their individual components. So each drug makes the other one work better and, as a result, we have a very effective new therapy for advanced bladder cancer.

Dr. Vadim Koshkin:

So, who is this treatment actually intended for? It’s important to you know, really specifically highlight who is this treatment right for at this time. So this is a treatment for patients who have advanced bladder or urothelial cancer.

Bladder and urothelial cancer are words we often use interchangeably, but they’re actually a little different. Urothelial just refers to the type of cell that lines both the bladder but also the rest of the genitourinary system, so including the ureter, so the tubes that lead to from the bladder to the kidneys, and even the entrance to the kidney is lined by these cells. So these cells, when they become abnormal and cancerous, can lead to urothelial cancer arising anywhere, not just the bladder but anywhere in genitourinary tract.

This combination is appropriate for actually patients with tumors arising anywhere in the GU tract. However, patients have to have metastatic disease, at least at this point, to receive this treatment to actually benefit from this treatment. That may change actually just in the very near future, and we’ll talk about that in a little bit, a bit later in my talk.

But to tolerate this treatment, it’s also important to keep in mind the patients have to have a good functional status. What I mean by that is this is a treatment that can have, of course, side effects. You have to be in reasonably good shape to be able to withstand that. That’s why that’s a very critical consideration for any you know, doctor who, of course, treats patients with this disease.

Then, of course, if a patient already has some of the side effects that can be worsened by some of these drugs, and we’ll discuss what these side effects are a little bit later, then we’re also pretty cautious about administering this treatment.

Dr. Vadim Koshkin:

Before moving further, I also want to discuss the importance actually of precision medicine in cancer in general and in bladder cancer in particular. What I want to highlight is that you know, the entity, we call it cancer certainly, or even the entity we call bladder cancer, encompasses a whole wide variety of tumors, and each tumor is, in particular, pretty different from the next. Each tumor has a unique pattern of mutations that’s almost like a fingerprint that may make it more or less vulnerable to certain treatment.

And so, with certain tumors, they have, for instance, expression of certain proteins like HER2, which makes them vulnerable to certain medications, which means we could you know effectively treat them with those drugs. Other tumors have mutations like in a protein called FGFR3 shown here, which, again, make it vulnerable to another type of drug.

But really across the board, many of the urothelial or bladder tumors have expression of this protein called nectin-4. That is the target of enfortumab vedotin, and that’s what in particular makes this such a useful combination. We don’t actually even have to test the tumors for expression actually of this protein to start this combination treatment because most urothelial or bladder cancers we know will express nectin-4.

Dr. Vadim Koshkin:

So why is this combination considered such an important option for advanced bladder cancer? Well, as I just mentioned, nectin-4 is very commonly present on the surface of bladder cancer cells, and it is a great target for enfortumab vedotin. Enfortumab vedotin works very well specifically in this situation.

Patients treated with this combination have significantly better results and outcomes than historically we’ve seen with prior treatments for bladder cancer, in particular with, for instance, chemotherapy. The prior standard of care in bladder cancer before the advent of this combination was chemotherapy with a drug called cisplatin or carboplatin, and that was the standard of care for several decades, for about 20 to 30 years, until this trial of enfortumab vedotin and pembrolizumab was able to demonstrate the superiority of this combination to chemotherapy.

Now that this combination has been approved, at least in the United States, for some patients, it’s been approved for over two years now, really since April of 2023, and across the broader spectrum of patients with urothelial cancer, it has had a full FDA approval since December of 2023. So now for almost a, well, soon it’ll be two years, we’ve had a lot of experience also with this combination in a real-world setting, so outside of clinical trials, which, of course, is a very different, you know, group of patients than those patients who are in clinical trials. But we’ve seen the same impressive outcomes, and this really suggests that this is a very, very effective treatment.

Dr. Vadim Koshkin:

Here’s what I mean by this. We see actually much higher responses with enfortumab vedotin and pembrolizumab in comparison to platinum-based chemotherapy. What I mean by responses here is a reduction in tumor size or tumor volume that we see on scans after starting treatment relative to before treatment.

In oncology, there are specific definitions of what a response means, but suffice it to say, it means a significant reduction in tumor size. With enfortumab vedotin and pembrolizumab combination, we see this significant reduction in more than two thirds of patients treated. In another probably 20 to 25%, we also see stable disease, meaning the tumor shrinks a little bit, but maybe not significantly, but at least it doesn’t continue growing. Only a minority of patients who start this combination of enfortumab vedotin and pembrolizumab, actually less than 10% of patients, does the tumor continue to grow even as they’re being treated and, as a result, we have to switch to something else.

So these are numbers that are much better and superior to what we’ve seen historically with platinum-based chemotherapy. We saw responses of about under 50% and probably disease control rate or basically clinical benefit, meaning response, and stable disease probably in the 60 to 70% range. So we see much higher responses with enfortumab vedotin and pembrolizumab versus chemotherapy that was used previously.

The overall survival is more than double with this combination also relative to chemotherapy. As I mentioned, more than 90% of patients with enfortumab vedotin-pembrolizumab have response or stable disease after they start treatment. Among those who have a response, that’s this 68% almost of patients, about half, or actually a bit more than half, are still in remission about two years later.

Among those patients who have a complete response … And what I mean by complete response is a complete disappearance of tumor on scans, and that’s almost a third of patients here, so 30% who start enfortumab vedotin and pembrolizumab, which by itself is a, you know, much higher number than what we’ve seen previously. But among those patients with a complete response, three-quarters, so 75%, maintain a complete response two years later.

Dr. Vadim Koshkin:

Based on all this, enfortumab vedotin and pembrolizumab is the preferred therapy for patients with newly diagnosed metastatic urothelial cancer. It represents a new hope for many patients with this advanced disease, and because of these very durable and deep responses that we see, many of these patients potentially are actually cured. It may be a bit soon to say that just because there have only been a few years of this data, but it really gives us a lot of hope that for many of these patients that have had complete responses, the cancer had gone away and hopefully will not come back.

It’s the fact that we see these very durable responses that is … As we sometimes do specifically with treatment regimens that include immunotherapy like this one, that’s what really, I think, is really exciting and encouraging here.

Dr. Vadim Koshkin:

But, of course, the flip side of any treatment are the side effects. And so, there are specific side effects to this combination as well that any patient starting on this, and of course their physicians who are prescribing this, should be very aware of and actually should monitor.

So a common early side effect or toxicity are skin toxicities or skin reactions that mostly are pretty manageable. They usually present as rashes that we can manage with steroid creams or things like that and really continued treatment. But in rare situations, these can be more severe skin side effects, sometimes even life-threatening. So that’s certainly something we pay very close attention to and keep an eye on.

Over time, in particular as patients stay on the treatment longer, many patients develop peripheral neuropathy. What I mean by that is that’s a side effect that really affects the tips of the nerves, and specifically the tips of the nerves in the extremities, so in the hands or in the feet. Usually it starts as not as noticeable a side effect, usually as a mild numbness and tingling that, you know, does not affect the patient’s day-to-day, but, over time, that really can change substantially such that if you have significant neuropathy in your feet, for instance, and you’re having really trouble feeling the floor, that will affect your balance and that can affect your gait and even basic walking, right.

Neuropathy that’s in the fingertips and that eventually progresses, can affect a myriad of things that we do with our fingers, right, things like buttoning shirts and tying shoelaces and holding utensils and writing, really things that often we take for granted but that are critical for day-to-day. And so, neuropathy is usually something that develops later after a while on this treatment. It’s specifically related to enfortumab, so the antibody drug conjugate, rather than to pembrolizumab. And it is something we need to keep a close eye on because it often then later on requires dose reductions of this drug to manage it effectively.

Other side effects that are perhaps not as common, both that we monitor also carefully and that we pay close attention to, include lung inflammation, also known as pneumonitis. That’s not as frequent with this combination, thankfully so, but can be more significant, right, because that’s something that affects your lungs, your ability to breathe. We don’t want it to get to that point either. That’s usually, we initially appreciated on scans, so just as patients who basically get CT scans while on treatment and we see changes in the lungs, before symptoms develop. But it’s critical to withhold the medication before further development of these symptoms.

Additionally, many patients who start on this treatment have high blood sugars as well or develop high blood sugars. This includes many patients who already have diabetes. So high blood sugar is a baseline, but actually many who do not and develop basically a new diabetes while on this therapy. That’s also very important and critical to keep an eye on and in fact, every time that patients come in for treatment with these medications, we in addition to checking other labs, also check their blood sugars.

Dr. Vadim Koshkin:

In terms of the timing of these side effects, as shown here and as we were just alluding to as well, something like high blood sugars, usually if it happens, happens early on. Skin reactions usually happen early on. Even severe skin reactions usually happen within the first couple of months, meaning that if you’re on treatment with this, it’s been several months, that’s a side effect that’s less likely to develop, but it can still develop at any point.

Sensory neuropathy, that’s again, that’s a numbness and tingling in the fingertips or feet. Significant side effects with that usually happen after about six months of treatment. But earlier and more indolent side effects like that can happen after about two to four months and that’s when it’s important to really start paying attention to this because, again, it’s important to take action and do something before it develops to this significant neuropathy. It’s important to not let it get to that point. And then lung inflammation really also can happen at any point, but, on average, it’s after about four months of treatment.

Dr. Vadim Koshkin:

So, what kind of monitoring do patients need while on treatment with this combination? Well, it’s really just monitoring for the things that we were just discussing as the major side effects, this means monitoring for skin rashes and other skin side effects. Again, particularly early on in treatment, which is when we start. As most side effects, they usually start to a more limited extent, but then, you know, can get worse and exacerbate quite quickly. The key is to act before that happens, and certainly before more severe skin reactions happen.

It’s important to monitor for progression of neuropathy. As I was mentioning, this is definitely something that usually starts out in a more indolent way, something that doesn’t bother patients, but then can get significantly worse. We don’t want it to get to that point. We want to act before that happens.

It’s critical to monitor blood sugars every time patients are come in for treatment. These are both infusion medications. So every time they come into infusion, we check their blood sugars. It is also critical to monitor functional status and things like appetite and potential weight loss and weight trends in general. This is, of course, done during doctor visits, but it’s also done by patients and family members at home. In particular for elderly patients, with this combination, I also do see more of an effect on appetite and potentially subsequent weight loss. So definitely something to keep an eye on as well.

Again, especially critical, and I can’t highlight this enough, is really listening to the patient, is of course critical for the doctors and the healthcare teams, but also you know for family members and caregivers. That’s why in particular, I think, for a webinar like this, it’s very important to have a patient voice here today as well, which I’m glad that we do.

Dr. Vadim Koshkin:

A question that patients very frequently ask about this treatment, certainly me and I know others as well, is, “How long am I expected to stay on this, right?” That’s a very good and a very reasonable question to ask, right. You know, historically, for many of our other treatments, the chemotherapy that I was alluding to earlier, it had a finite

course, simply because it has a lot of side effects. Patients just really can’t stay on it longer than usually the fixed four to six cycles.

With this, it’s a little bit different, but because, you know, in the clinical trial of this combination, really these drugs were given indefinitely, that is what we do in the real world as standard of care practice now as well. But of course most patients also don’t stay on any treatment indefinitely, right.

In general, with this treatment, it’s given in 21-day cycles, and in a given 21-day cycle, patients receive both drugs. So in enfortumab vedotin and pembrolizumab on day one and then only enfortumab vedotin on day eight. For the remaining two weeks, they don’t get treatment, and then we repeat the whole thing again.

In the real-world setting, most patients can expect to stay on treatment for at least several months. This is, of course, assuming that you go on treatment and the treatment is working, which is, again, the case for over 90% of patients. So you can say that that’s probably how you can expect things to go.

But I think the information from clinical trials is important to tell us in general, on average, how long patients there stayed on this treatment before, you know, coming off, usually often due to side effects, maybe sometimes due to other things like patient preference. What we see is that, on average, patients stayed on enfortumab vedotin for about nine cycles. Nine 21-day cycles is about six to seven months. They stayed on pembrolizumab, the immunotherapy drug that doesn’t have as maybe prominent a side effect profile, for a little bit longer, for about 11 cycles. That equates to about eight months.

Now if patients are responding to treatment, they have a complete or partial response as shown here. They stay on either drug longer. If they have had a complete response in a clinical trial, they stay on treatment the longest. Then that, of course, makes sense, because if the treatment is working, they generally would stay on it.

But, again, it’s important to keep in mind that side effects, especially neuropathy, accumulate over time as well, in particular, you know, as the patient continues on treatment with enfortumab vedotin. That’s when we often have to make critical adjustments.

Dr. Vadim Koshkin:

So, with that, what do we expect with this treatment? Well, as I was mentioning, when a patient is on treatment for at least several months, it likely means that the treatment is working, right. We wouldn’t keep going. If, of course, the tumor was growing, in that situation, we would switch to something else.

What that means is that, over time, side effects can accumulate as well. There is a cost, unfortunately, to that success of treatment. And so, it is, you know, in my experience at least, critical to highlight to patients from the very beginning that, especially if things work and you’re on this treatment for a while, we will eventually be reducing dose. We have to be you know very candid about your experience on the treatment, about the side effects you’re experiencing to, you know, allow us to do that basically correctly and to allow you to stay on treatment longer and potentially benefit from it more.

Because many side effects can certainly improve and many can resolve with stopping treatment, but some are much more challenging, and neuropathy is such a side effect. If it gets really bad before we discontinue it, in many cases it won’t improve all the way back to normal. That’s why it’s especially important to not let things get to that point.

But, again, we have some useful information from clinical trials to guide us in this situation. This suggests that treatment modifications or dose modifications, meaning reducing dose or maybe pausing treatment for a bit, occurred in the majority of patients. More than 50% of patients who start this treatment can expect to basically either reduce dose, interrupt treatment at some point.

Again, that is to be expected. It doesn’t mean that anything really is going wrong. In fact, it happens more frequently in patients who have responded. It’s probably because they’re on treatment longer. But, again, doing this, adjusting dose, often decreasing dose of enfortumab does not necessarily compromise the efficacy of treatment. I know that’s something that many patients worry about and so, I think that’s, and rightfully so. I think that’s an absolutely critical thing to highlight. Again, the fact that many patients, about 50% basically, will have a dose reduction. Among responders, that number is actually higher, it’s over 50%.

Dr. Vadim Koshkin:

It’s also important to consider, despite this being such a promising and effective regimen, that it’s not actually the right treatment for some patients. So which patients should not get this treatment? Well, certainly those who already have very significant neuropathy, and that can happen, neuropathy can happen for other reasons. It can happen due to prior treatments. It can happen due to diabetes, that affects your nerves as well. Sometimes it happens for unclear reasons, many patients have what’s called idiopathic neuropathy.

But if they already have a pretty significant neuropathy, starting on this treatment will certainly worsen it. So for those patients, we have to be pretty careful, and some of them actually, maybe we should look for other treatments that do not have the same side effect.

If they have a functional status that is impaired and not necessarily due to untreated cancer, so maybe patients who are significantly frail such that a more aggressive cancer therapy like

this can actually make them a lot worse, that’s a situation in which we should exercise significant caution as well.

Then important thing to consider in any treatment that includes an immunotherapy drug as part of the combination is that many patients actually cannot get immunotherapy drugs. So it’s dangerous for them to get drugs that activate or rev up their immune system and that could be because they can have a condition where their immune system is already overactive or revved up. So, for instance, patients with poorly controlled rheumatoid arthritis or patients with inflammatory bowel disease, like ulcerative colitis or Crohn’s disease, you know, giving them pembrolizumab will likely significantly worsen those and may not be worth it.

Then an important consideration, of course, with patients with history of organ transplants as well. These patients are generally already on immunosuppressive medications we’re actually were trying to not make their immune system overactive, but actually tone it down so that it doesn’t attack and reject the transplanted organ.

For such patients who are often on medications that actually suppress their immune system, if you give them a drug that actually enhances and revs up their immune system, they’re for sure going to reject that organ, and we want to avoid that. For patients like that, we may be able to just consider enfortumab, for instance, and not the immunotherapy drug pembrolizumab.

Then an important considerations for patients with diabetes, as I mentioned, blood sugar control is an issue with this combination or can be an issue, but I will highlight that patients with diabetes can receive this therapy. Diabetes is pretty common, and it’s pretty common in this population, unfortunately. It doesn’t mean that it rules you out for this treatment, but such patients, of course, should be monitored pretty carefully.

Dr. Vadim Koshkin:

So what are some of the important things to actually discuss with your doctor and with your healthcare team about this therapy? Well, it is important to be on the same page about what is the goal and expected outcome of this treatment, right? Different patients, I think, have very different goals, and it’s important to understand that from the outset. For that reason, discussing your expectations with your physician, your healthcare team is, of course, critical as well. The expected duration of treatment and side effects, very important here and you know, we discussed some of that a little bit earlier.

Then I think it’s important to define, or at least discuss, what does success look like with treatment like this? What are we aiming for? Again, this is very different for different patients and can be affected by a wide variety of things, right. An absolutely critical thing is to always discuss the extent of your side effects actually after already starting therapy with your doctor, because, again, I think that’s an absolutely critical part of successful treatment, because it does affect how we give this regimen, how we adjust doses, and really, really, what we do. For a patient to exercise and express themselves and their voice in that situation is absolutely important.

Dr. Vadim Koshkin:

So, what is the future of this therapy? Well, increasingly I think we will see more and more patients with urothelial cancer receiving this treatment. Actually, even in the time since I made the slides, which is just earlier this week, this is already proving to be the case, because just a couple of days ago, we actually heard a press release from results of a clinical trial of this combination for patients now with metastatic disease, but with muscle invasive bladder cancer so patients who are treated with this therapy, this combination treatment, followed by a surgery to remove the bladder, with the attempt to, of course, get rid of the cancer completely to cure it.

There is a clinical trial that investigated this combination treatment specifically in that patient population that we now know is positive, meaning it’s better than the prior standard of care, which likely means that in the coming you know, months, two years, the FDA will likely approve this therapy. Again, we have to see the data first, but usually positive trial, big positive trial like that, leads to an FDA approval for a very different and a broader patient population, those with muscle invasive disease.

And so, I think you know, when we talk about this combination a couple of years from now, it’ll be a much broader population of patients that is being treated with this. We will have a lot more with this therapy. We’ll have more information about you know, side effects as well and their expected resolution as more and more patients are treated with this.

Dr. Vadim Koshkin:

So, to summarize, enfortumab vedotin-pembrolizumab, the combination we’re discussing today, is a very effective treatment option for patients with advanced bladder cancer. It has led to significant strides in the care and treatment of patients with this disease, and you know, that has changed even, again, in the time since these slides were made earlier this week. It significantly exceeds outcomes, this combination, relative to you know, what we were seeing with prior standard of care therapies like chemotherapy.

But, on the other hand, it is associated with a specific side effect profile that, you know we have to keep in mind, we have to monitor and manage very carefully to really allow more patients to achieve greater success on this treatment. With that, patient communication with their treatment team is absolutely key and absolutely critical. That’s why, again, I think it is especially important to hear the patient voice in all this and really how this treatment, you know, affects your day-to-day and how it really can help many patients. That’s why I’m really glad that we have a patient today to describe their experience with this as well.

Dr. Vadim Koshkin:

But in the meantime, I, again, thank you for your attention with this, and look forward to the questions in a discussion later.

Robert Ashton:

All right. Thank you so much, Patricia, and thank you for the introduction earlier. Just to add onto the introduction, Patricia mentioned that I have a part-time job of consulting. I also have a second part-time job, and that’s my cancer treatment.

I do approach it as a job. I was diagnosed with stage two bladder cancer in the fall of 2016, and it has since progressed to stage four. I’ve gone through numerous treatments, from procedures and surgeries, immunotherapies, chemotherapies, radiation in various combinations and currently, I am on the enfortumab-pembrolizumab combination. I started enfortumab in November of 2022 and added pembrolizumab about one and a half years ago.

So far, I’m having a good response to it, to the treatment. It has manageable side effects for me at this time. It’s mostly fatigue. I can’t blame all the fatigue on this combination, though. I’ve been fatigued for some time with all the therapies I’ve been on. I do have a bit of neuropathy in my hands and my feet in the form of numbness, and I have a variable appetite. Some days I’m not hungry at all and some days I want to eat the house down.

The other thing I wanted to point out for this therapy is I do find it relative convenient to take. On those days, on day one of this 21-day cycle, when I receive both the enfortumab and the pembrolizumab, the infusion time is a total of one hour. It’s 30 minutes of time for each drug, which adds to 60 minutes. If you’ve been through other treatments, for instance, cisplatin or some of the other platinum-based drugs, you know, they can take a lot longer and you may lay in the infusion center for some time. So that’s one thing I really appreciate about this combination.

You know living with cancer since 2016 has taught me several things, and Patricia asked me to share some of these with you. First and foremost, I’m much more thankful than I ever was. I’m thankful for every day that I have, as well as the people in my life, both the old and new folks who I’ve met along the way. I’m thankful for the experiences I’ve had, as well as learnings that have changed and altered me and how I behave.

I try to live in the present and have no regrets. A little bit easier said than done, but I do focus on the now, not the past and not too far in the future. I live with what’s called an open hand, which is letting go of those things that really don’t matter and try to capture all the good things that come along. I do try to be more kind and patient, another thing that’s a work in progress, but still achieving to be better.

Lastly, one of the things I think we’ve all probably learned about ourselves is that I’m stronger and braver than I ever thought I was, and so are you in the process, I know. While I realize I’ll ultimately lose this war, I’ve been fortunate to win a lot of battles with the help of many people. I continue to learn about the disease and living with cancer.

Again, I want to thank Dr. Koshkin and the Bladder Cancer Advocacy Network for inviting me to be here today and sharing some of my experiences with everyone.

Patricia Rios:

Thank you, Robert, for accepting our invitation and being able to share your experience with others. You talked about some of the side effects that you experienced, fatigue being one of them. Could you tell us a little bit about how you manage that particular side effects or others?

Robert Ashton:

Sure. You know, everyone’s cancer experience is different, and obviously I can only speak to mine, but the symptom that I have that affects me most on a daily basis is fatigue. As I said earlier, I can’t blame this entirely on my current treatment with enfortumab and pembrolizumab. You know I’ve been on therapies for some time, and my fatigue goes back for some time as well.

But I typically try to fight this in two ways. First, I rest when I need to rest. I try to plan my days to ensure I have time built in to rest should I need it. And to be honest, I’m okay with going to bed by 9:00 PM if I need to.

Second, I try to exercise regularly. Most often the form of foot walking is I get both a physical and mental benefit from it. I had a, well, a very wise nurse once told me that exercise is the enemy of fatigue. She told me that if I can’t walk for 20 minutes, to walk for 10. If I can’t walk for 10 minutes, then walk for five. Her main message was just get up and move. And it’s true. You know the hardest part is just getting started each day.

Patricia Rios:

Thank you for sharing that tip. That leads me to wonder, Dr. Koshkin, you shared many different side effects that result from this therapy. I’m curious to know, what are some of the, who else is part of, I guess, the team that helps manage patients, and also what are some of those surveillance or tests that are done as patients are on these treatments, besides the ones that you mentioned during the, your presentation?

Dr. Vadim Koshkin:

Yeah, that’s a great question. I think it’s absolutely important and critical to highlight the importance of the healthcare team right, which is so much more just than the physician. You know, Robert knows all these people on my team cause you know he they interact with them very closely. But it’s you know the nurses who you know work closely with me and then work closely with patients and you know help patients manage side effects and then communicate those to me and communicate other things to me that patients express.

We have nurse practitioners as well who you know are able to see the patients and also prescribe medications and prescribe certain interventions in actually the same way that physicians can. There are you know actually non-medical … Well, non-clinical personnel, I should say, so the schedulers who make sure that you know the infusion of a you know given treatment is timed correctly with you know the appointment and things like that.

I think their role in helping patients navigate all that is very important. Then we have a lot of colleagues from other teams that help manage, you know, side effects or some of the other complications as well. So Robert mentioned things like fatigue right, and I would add to that appetite loss and other symptoms you know that our symptom management colleagues actually help with a lot and that’s, those are additional doctors and additional nurses and nurse practitioners who work with them, who focus on that aspect of cancer care, right, which goes in parallel with treatment, but is, you know, probably just as critical. It’s actually making sure that the patients can feel better and, you know, deal with and tolerate some of these challenging treatments better as well.

Then, of course, if more significant or, well, I shouldn’t even say more significant, but side effects that require other medical input happen. So things like, you know, inflammation in the lungs that I was alluding to earlier, then we often involve other physicians as well, so like pulmonologists that focus on the lungs or physicians that focus on the liver or GI tract. So it, in many instances … Oh, dermatologists as well; that help with rashes that are a common side effect here. So in many cases like that, it ends up being quite an extensive team that a patient interacts with. We’re talking about tens of people right and quite a lot.

Patricia Rios:

Thank you for explaining that and I know that’s something that came up when Robert and I were discussing and he was praising his team at UCSF. I’m curious to know, in terms of the how widespread this treatment is available, is it available outside of non-academic centers, say, for example, community-based practices?

Dr. Vadim Koshkin:

Yeah, at this point is is. As most treatments in oncology, initially when it’s part of clinical trials, it’s only available, yeah, at academic places that run those trials. Although many community practices now actually run clinical trials as well, right? So you can seek out that therapy there. But once it’s well FDA approved and more widely available, you can really get it anywhere.

I think there is some geographic variability with uptake of this particular regimen. I think certainly, well, in Northern California where I practice, I think it’s been, you know, pretty widely used. I don’t know if that’s the case in all areas of the country, because actually, I mean, we’ve seen actually some data that yeah, in many places, it yeah hasn’t actually probably been used as broadly as it should be given the really positive data we’re seeing, right?. So in some places, you know, it still, you know, prior therapies like chemotherapy are being used when, you know, I don’t know that there’s a strong reason to do that.

But, overall, I mean, yeah, I think in the last year and a half, we’ve seen a lot of uptake with this. We have, you know, pretty good data now again suggesting how patients would this do in what I call the real-world settings, so outside of clinical trials, but in everyday practice.

Patricia Rios:

Thank you for sharing that. I have a follow-up question, but I’m going to; I’m looking at all the questions on the Q&A box, so I’m going to go through all of those because there’s a lot coming through and so, just a few … We will go a little bit over our scheduled time. And so, please stick around. So one of the questions from one of the participants is why doesn’t the cancer that has metastasized to the adrenal gland respond to EV-pembro?

Dr. Vadim Koshkin:

Well, I mean, to my knowledge, that’s not, you know, usually the case. I mean, you know, the different cases are different, so there may be situations where, you know, in particular cases that metastasis did not respond to treatment. But, I mean, I can certainly think of, you know, patients who I’ve had that did have that metastasis and it did respond.

So I don’t think there’s anything kinda specific about that location that, you know, indicates this therapy doesn’t work as well. To my knowledge, there isn’t really … I mean we have looked at this actually, looking at are there sort of specific situations in which it wouldn’t work as effectively like based on the spread of disease or something else, and we’re not really finding a lot.

I would say just the situations where maybe we’re not as sure about, you know, the efficacy of this regimen are in bladder cancers that are not of the typical urothelial histology. So basically a slightly different subtype of bladder cancer that maybe doesn’t express the target of the drug, of enfortumab vedotin, called nectin-4 as much. But even in many of those cancers, we still do see responses with this therapy.

Patricia Rios:

Good to hear. What is the maintenance protocol after the tumor has been eliminated? You talked about complete response and response … What’s the surveillance and just maintenance?

Dr. Vadim Koshkin:

Yeah. So at this point it’s really quite variable, I would say. So usually if a patient has been on, you know, treatment with this for a few months, have had a complete response, meaning, you know, you have tumors on scans before treatment, then, you know, after starting on treatment, you get the same scans and the tumor isn’t there, right.

So then we usually, you know, still continue treatment with both drugs for at least some time. There isn’t, I would say at this point, a magic number or time when we can definitely say like this is, you know, this is the limit of it. At least we don’t have that data yet. So because of that uncertainty, we usually continue it for some time, but keeping in mind the side effects, right? Because, again, you know, a patient has responded to treatment completely, but if they start, you know, developing more neuropathy, I would be probably more aggressive about, you know, stepping off of the treatment and maybe stopping at least one of the drugs, like enfortumab, in that situation.

Then oftentimes the … To address the question directly, the maintenance ends up being pembrolizumab alone. So we stop enfortumab, the drug that probably causes more side effects and continue the immunotherapy drug that still is sort of working on your immune system, but usually doesn’t cause as much side effects and we continue that for a bit longer.

But then, you know, if a couple of years down the line, or even less amount of time, we, you know, are still in a complete response, we could, you know, stop therapy altogether and then just monitor with scans. I do, though, you know, continue monitoring, and I want to emphasize that that’s, in particular, important, right, you know, that we still … Even patients who stop treatment, who are in, you know, that very good situation where they can stop treatment, we still watch things with scans every few months just to make sure that if there is a, God forbid, you know, recurrence of the cancer, that we can, you know, address it promptly and potentially restart treatment.

Patricia Rios:

This is kind of related, you talked about perhaps stopping EV. What, is there a recommended like low dosage where it may become ineffective, or is it stopping it altogether the best approach?

Dr. Vadim Koshkin:

Yeah. So we have, I would say, a pretty well-worked out protocol, again based on experience from clinical trials, of how to reduce dose. There are basically four different dose levels of enfortumab that we use, starting with the highest dose, and then we can reduce it about three times before we have to stop it kinda completely.

But the decision to stop completely, at least in my practice, centers more around the side effect. So if we are getting to the point where I feel like, you know, we’ve gotten all the benefit, most of the benefit that we can from this and further treatment just, you know, causes more neuropathy, causes more discomfort for the patient, that is where I would probably step off and stop the drug.

Keep in mind that, again, you know, the cancer has never been able to progress and grow successfully on treatment, meaning that if there is a recurrence later, we can still retreat, right? retreat with this combination.

Patricia Rios:

I don’t know if we had too much time to talk about how the medications are administered. And so, one of our listeners wants to know how is it dispensed in the body. Is it directly into the bladder or intravenously? That question is for both. Dr. Koshkin, if you can, you know, speak about how it is administered and, Robert, your experience with that piece.

Dr. Vadim Koshkin:

Yeah, I’ll just say quickly that this … So this specific combination that we’re talking about here is given intravenously, because this is meant for treatment of metastatic or systemic disease, so cancer that’s potentially anywhere in the body, places where we can see it on scans, but also other places where perhaps it’s microscopic. So it goes in your vein and technically all over the body, right, not just inside the bladder as certain treatments do. When you’re early on in the treatment course of bladder cancer, it’s limited just to the bladder. Then in terms of how the experience goes with getting these drugs, that’s, I mean, yeah, certainly something Robert can speak to more.

Robert Ashton:

Yeah. As Dr. Koshkin said, it is delivered IV. I do have a port, so it’s delivered through my port. As I mentioned, it’s an infusion on day one when you get both medications, about an hour total time because each drug is a 30-minute infusion. And so, they just access the vein as they typically would with any other IV drug, and then they, it’s administered via the pump, and then you’re on your way. So compared to several of the other therapies I’ve been on, this one’s pretty easy to take.

Patricia Rios:

Good to know. Speaking of … Well, there is a … We talked about whether this is available in different settings, academic versus community. I’m curious to know in terms of coverage insurance, are there any limitations cost-wise that patients should be aware of?

Dr. Vadim Koshkin:

Yeah. Well, again, I think I’ll probably address it maybe from my end, and then Robert, hopefully, can speak to this as well, just because this is another topic where I think the patient voice is probably a lot more critical than mine. I will say that when a therapy is FDA-approved like this, insurance should cover it, right. But of course that is a blanket statement that applies very differently, I think, to different people.

So, yeah, there should be no issue with getting this, you know, reimbursed by a coverage plan, because as long as, again, it’s being used in the correct circumstance, which is for, you know, advanced bladder cancer, as I mentioned, it will probably be expanding to a broader population of patients based on, you know, additional trials that are coming out as positive in patients with muscle-invasive disease. That is not the case yet. So technically right now we would not be able to use it and for it to get reimbursed in that situation. But that’s probably, probably coming down the line.

But, yeah, so from a physician end of things, I’ve not had, you know, situations where you order this regimen and the insurance company blocks it or rejects it because, again, it’s an FDA-approved drug, the way that they can reject certain other things, even like scans or things like that. But, you know, these are very, very expensive drugs, I mean both of them. If this is something that someone would pay for out of pocket, which no one should, it’s tens of thousands of dollars per dose, right. So not something anyone would really consider reasonable.

Then, of course, depending on your specific coverage and plan, that even a percentage of that, I think, can still hit a patient significantly. I don’t know, if Robert, if you have more to add to that.

Robert Ashton:

No, I would only add that it’s going to be variable by individual plan and what they cover. Fortunately, my insurance does cover it, so I have no out of pocket for the infusion cost or the drug itself. But as Dr. Koshkin said, it is, by their own, it is extremely expensive. However, it is an FDA-approved treatment and therapy. But it does go back to the individual plan and what they cover.

But I switched insurance companies, and it wasn’t preapproved yet for the first dose that I got, but it was approved shortly thereafter.  And in fact, they approved me for a total year. So they knew that once you start, you’re probably going to be on this for a while, and they didn’t want to have to go through this all the time. But it will be variable. But I haven’t heard of any specific individuals that were rejected for it.

Patricia Rios:

Thank you for sharing that. So looking at the time, I have two questions for you, Robert, and one for you, Dr. Koshkin. One of the questions is the same one for both of you, but what I’ll do is; Robert, this question was directed to you. What advice or what would you say to a patient that’s considered this treatment option?

Robert Ashton:

I’m sorry, Patricia, you broke up just a second.

Patricia Rios:

Oh, so sorry. Let me try again. This is a question from one of our audience participants who wants to know what piece of advice would you give to a newly diagnosed patient contemplating whether to receive this treatment or not?

Robert Ashton:

Yeah, I think if you’ve been newly diagnosed first, I would recommend you take a deep breath. The diagnosis is a lot to take in. But, second, my advice is just be curious. Learn as much as you can, not just about the treatment, but also about the disease. You know, Dr. Koshkin’s overview was very helpful, talking about how it works, et cetera, and what is its benefits over others, as well as also what are some of the challenges with the medication.

So, learn as much as you can, as well as take advantage of all the resources you may have available and these include everything from your healthcare team, your oncologist to radiologist, the nurses, technicians, and all of the other healthcare professionals that you’ll meet along the way. They manage this disease every day as well as work with this combination. I’ve always been impressed by how much knowledge they can share.

The other place I would look to is patient associations like the Bladder Cancer Advocacy Network. They offer a wealth of resources where information and help can be found on an easy-to-access website. Another place is your cancer support services that’s may be offered through your local hospital, that will be … They can give information on some of the things that support you around the treatment of the disease, as well as speak with other patients that are going through this, and particularly those that are having the drug administered. You know, how are they responding to it? How are they tolerating it, et cetera?

I think it’s a great combination. It has really kept my disease stable in majority of the cases, and much longer than I had anticipated personally. So I’m thankful it’s here. It is relatively well-tolerated. I think Dr. Koshkin did a great job of covering what the side effects are. Just continue to learn more about it and speak with the experts who use it on a regular basis, and experts including patients.

Patricia Rios:

Thank you for the special recognition to BCAN. Dr. Koshkin, there’s a lot of questions in the chat about dosage, restarting, and effectiveness. I’m curious to know if you have some sort of general advice to those who are joining us today, who need a little bit more guidance or information about how to proceed now that they either have started treatment, stopped, or are not sure, you know, if it’s working.

Dr. Vadim Koshkin:

Yeah, all of these cases are so individualized, right, and so different, I think, from each other that it’s hard to give like a blanket statement as guidance. In part, that’s what, you know, clinical trials try to do is that everyone basically usually gets the same thing or there’s a strict set of rules that guide sort of what you do if something happens. But then when this therapy becomes available for the broader population in the real world where we’re using it for now thousands of patients, then it’s you learn as you go along and you acquire those experiences.

So I would say, again, it’s very variable what you do in different situations in terms of situations in which you would reduce dose or maybe stop the treatment and give patient a treatment break altogether, right.

And so, the key thing, again, I think for the patient to be aware of and to do, and I try to highlight that in my presentation as well, is just to be pretty candid about their side effects and what they’re experiencing, right, because I mean sometimes, at least what I found, some patients are worried about endorsing side effects too much with a concern that this will, you know, … a treatment that’s working will be pulled back.

But it is really, again, just critical to do so because it allows us to, I think, more effectively dose the drug, right, and really, I think, help patients more and more effectively and not allow for the side effects to get worse and then impact really the treatment going forward. But aside from that, yeah, I mean I think in a lot of situations, even after a, you know, patient has been on this treatment and they take a break, we can resume treatment and it still works. We’ve seen that quite a bit.

We’re also now learning we have other approaches and other biomarkers that we use. So not just CT scans, but things like tumor DNA. So that’s a blood test that we also use to monitor therapy. Right now we mostly use it for patients actually with earlier stages of disease, so muscle invasive disease. But actually we can use it for monitoring on any immunotherapy regimen as well.

That’s something that we’re kinda using more and more and I think becomes a very useful adjunct to know when to discontinue treatment, when to resume it again. I think, you know, when we have this conversation two years from now, I think we’ll know even more than today and have more guidance and more sense of how to do these things.

Patricia Rios:

Thank you for answering that, and I think that is something we’re all looking forward to see where, what the future holds in terms of this therapy and how it can be used in other stages or types of bladder cancer.