Understanding the Expanding Role of Antibody-Drug Conjugates in Bladder Cancer

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Dr. Plimack:
Hi, I’m Dr. Elizabeth Plimack, and this is CME on ReachMD. Today, we’re going to be talking about adverse events seen with the newer bladder cancer treatments, and we’re going to focus on the patient experience.

So, enfortumab vedotin plus pembrolizumab has unprecedented efficacy in the treatment of metastatic urothelial cancer. But there are side effects that are really unique to this combination and sometimes challenging to manage. I’m going to focus on the top three that sort of are the most unique.

One is skin reactions. So, really, that’s a synergistic adverse event with the combination of EV and pembro, where we can see rashes, sometimes severe. The second is hyperglycemia, so we can see increases in blood sugar on the treatment either because of the treatment itself or an interaction with a preexisting diabetes. And then, one of the ones that we’re going to focus on today is peripheral neuropathy. This is the one that most often makes us stop treatment, even when it’s working, and sometimes can be hard to manage. It’s one that we manage mostly with dose reductions and breaks. And we’ll talk about that more in a minute.

Just briefly, to go over this combination, again, because of unprecedented efficacy, it works really well in a lot of folks with metastatic urothelial cancer. And so, more often, we’re stopping the treatment while it’s still working because of side effects instead of because it stops working.

It’s a good problem to have. We like having an effective therapy, but by nature, effective therapies are given to patients for longer, typically because it’s felt that they’re working, so we should continue. The duration of response data that we just saw at ESMO was really amazing. Definitely showed people doing well long term: out to 5 years. Really interesting, though; almost everyone has stopped treatment by 2 years.

And, again, that sort of speaks to this story of a very effective disease. Patients continue on therapy, but, ultimately, when it was stopped, we learned a lot of those patients continue to do well for years. So, it’s really encouraging us and helping us kind of shape how we think about and give these drugs together.

Usually, the time to first onset of the toxicities, it’s typically early that we see them, but some can be late. And then, also encouraging because there are a lot of dose reductions and dose modifications of the EV and pembrolizumab, there is some data from Dr. Petrylak and team showing that, even when we reduced a median duration of exposure, responses seemed to be unchanged. So, all this sort of speaks to us learning how to use these drugs a little bit better.

So, I have with me one of our patients, Lillibeth, who has the courage to sort of talk about and share her experience with this drug combination with us. Lillibeth started on EV and pembro about 9 months ago, and spoiler alert, I’ll give the great news that she is one of the people who had an amazing response to treatment. We can not find cancer anymore on her scans, which is great. But I’m going to turn it over to her to just sort of share the story of her journey on this treatment over the last 9 months.

Lillibeth, when you first started the treatment, what were sort of the early things that you experienced while on treatment?

Lillibeth: 
Okay. Yeah, initially it was kind of like a weird feeling because it’s like I had skin rashes, and then when I sweat, I feel like my body, like itches all over

Dr. Plimack: 
Yeah, common.

Lillibeth: 
And then I developed like hyperglycemia. I was so glad that I participated in  the clinical trials because your team were like monitoring me closely. And then there were a couple of times that we have to hold back the treatment because of the hyperglycemia.

And then eventually, I was referred back to my  primary care physician, who then, like, prescribed me to start on glipizide, but then she started me on a low dose to be on the safe side.

And at first, I was so frustrated because it was like I’m getting treated to get better. But then, the other hand, I’m put it on other medication because of the hyperglycemia, but I said, “This is you know part of the journey,” so I accepted it.

Dr. Plimack: 
You were amazing. You really did. You really worked so hard with us, your team, your primary care doctor, all the folks involved.

Lillibeth: 
Towards the end of May/July I was having numbness, and tingling sensation of my fingers, and my feet. The tingling and the pain gets worse at night, especially with my feet. There were like several times we would push back on the treatment, and then we decreased the dose.

Dr. Plimack: 
Right. We held the treatment. We decreased the dose. We did all of those things that are in the sort of guidance for this .

Lillibeth: 
And then it came the time that you referred me to see the support care team at Fox Chase, and I saw Dr.  ___. And then he prescribed me some gabapentin, and then I said, “Oh, here comes another medication.”

Dr. Plimack: 
Right.

Lillibeth: 
And then, with the gabapentin, he increased the dose one time, and I think after, like, my last treatment, I noticed that the tingling and the sensation, it didn’t make a difference with the gabapentin. So, —

Dr. Plimack: 
Right.

Lillibeth: 
And then he switched me.

Dr. Plimack: 
And how is your neuropathy now?

Lillibeth:
It’s a little bit better. I’m so impressed with myself, I’m able to tie the shoelace. But I stil cannot, like, do the fine, like, motor movements. 

Dr. Plimack:
It’s so helpful for you to share this. It’s true, like, the neuropathy it’s one of those things is the hardest for us to control and takes the longest to reverse —

Lillibeth: 
Yeah. It is Dr. Plimack, and, like, when we were at the clinic, I was, like, hoping and anticipating, that like, after this, once I get to, like,  the cycle of the treatment, I was hoping I would go back to my job. I could go back to work, but then you say, I remember you always say, “See how you feel. Don’t push yourself,” and then I did, and  because I said, “I couldn’t risk my job, and with the kind of work I have, I couldn’t risk it, just going back to work.

Dr. Plimack:
You work in a neonatal intensive care unit, right? 

Lillibeth:
Yeah, it was frustrating, but then I accepted it like this is part of my journey, so.

Dr. Plimack: 
Well, we’re here with you, and it’s all of our hope that this nerve endings start to heal over time. We know it can take a long time.

Lillibeth: 
Yeah.

Dr. Plimack:
And the fact that you can tie your shoes, that is a huge moment. We appreciate that.

Lillibeth: 
I said, “This is just like one part,” but like I consider like, my biggest winning is, like, when you gave me the news that, like, my last CT scan, that everything’s clear. So, I’m so glad I’m one of the patients who has, like, a good result with  the treatment.

Dr. Plimack: 
Yes. We are happy for that. We celebrate the good news whenever we get it, right?

Lillibeth: 
I was even happy, like, after I developed the colitis after the first combination of treatment, but then I remember you told me that I already got the benefit.

Dr. Plimack: 
That’s what we thought. Well, Lillibeth, you’ve been through so much: colitis, skin rash, hyperglycemia, and neuropathy. You’re sort of still piecing  all the side effects, but also the best result, right?

Lillibeth: 
In spite of all the hurdles.

Dr. Plimack:
Thank you so much, Lillibeth, for sharing your story. That’s all the time we have today.

Thank you for listening to CME on ReachMD.

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You have been listening to CME on ReachMD.  This activity is jointly provided by Partners for Advancing Clinical Education, Bladder Cancer Advocacy Network and RedMedEdand supported through an educational grant from Astellas and Pfizer, Inc.

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