A roundtable discussion, moderated by Peter O’Donnell, MD, discussed the advanced urothelial treatment landscape, as well as recent trial data from ESMO 2023. Dr. O’Donnell was joined by Terence Friedlander, MD; Matthew Galsky, MD; and Jonathan Rosenberg, MD.
In the next segment of the roundtable series, the panel shares tips for community oncologists who may not be familiar with treating patients with the enfortumab vedotin/pembrolizumab combination.
Dr. O’Donnell: We’re in a world now, where EV [enfortumab vedotin]/pembrolizumab is going to be readily utilized, but a lot of clinicians… At least when I talk to community oncologists across the United States, they don’t have a lot of experience with EV yet, even though it’s been out there since 2019. You made the point that they don’t see that many metastatic bladder cancer patients a year. What advice can we give? How can we help support those oncologists that are going to be using this regimen now, that maybe haven’t had a lot of experience with it? Because I think there is a big learning curve around it. Jonathan, I’ll start with you.
Dr. Rosenberg: As I think I’ve said, see them early and often in the course of treatment. Pay attention to painful or blistering rashes, because those are things that turn into nasty skin reactions that can be potentially life-threatening or fatal. The neuropathy is different than platinum neuropathy and taxane neuropathy. This is both a motor and sensory neuropathy, and patients can develop gait difficulties, imbalance. They’re eating food, they drop their forks. They can’t button their shirts, not because they can’t feel it, because they can’t actually do it. Pay attention to motor neuropathy as well as sensory neuropathy. That’s a longer-term side effect usually, after 3, 4, 6, 9 months, people start developing that. It’s not an emergent issue, but it’s something that you have to pay attention to. One of the most interactive things you can do is watch the patient walk into the room, and you will pick up on things that they won’t disclose to you.
Dr. O’Donnell: Matt, tips on using EV/pembrolizumab?
Dr. Galsky: Yeah, so 2 things I think both are in the package insert. But 1, it’s weight-based dosing of course, but there’s a cap. Just practically, you should be aware that there’s a cap in the dose. Then there’s dose holds in the package insert on day of treatment for glucose. We’re not so used to looking at glucose before we sign chemotherapy orders; it comes back later, but you have to look at it.
Dr. Friedlander: Yeah, I would just say, in having used this drug a lot, I counsel patients ahead of time about all these side effects. It’s a good chunk of what we talk about. I also tell them we’re likely to reduce the dose. It’s actually fairly common, at least in my practice, that we start at 1.25 and go down. I find patients fight less or resist less when they sort of are aware of that ahead of time. You can also point out that there are patients who get 1 mg/kg for fairly long periods of time, who do quite well. It’s not like you’re necessarily compromising all the efficacy of this drug by lowering the dose or taking a break or a hold.
Then, as was said, monitoring for neuropathy, which happens a couple cycles in. The skin toxicity happens really early. I tell the patients, if they notice a rash, they have to call us, because there’s been Stevens-Johnson, erythema multiforme, really bad reactions; people died of the skin toxicity. If they’re aware of this really early, and getting topical steroids, oral steroids, or dermatology involved, I think is really important. There’s also eye toxicity for this, ocular toxicity, usually the front of the eye, usually not too severe, but they should be aware of that.
Actually, alopecia happens with EV. It’s not that common, but I’ve had patients lose all their hair, and I never counseled them about that, and they were really distressed by that. Now that’s always part of what I tell them at the beginning, even if it’s a smaller risk of that, just because it’s really distressing.
Dr. Rosenberg: I do want to say that rashes, while they’re incredibly frequent with the combination, the vast majority of them can be self-limited or ameliorated with topical or oral corticosteroids.
Dr. Friedlander: I often give the patient steroids once they’ve had a rash, and I just tell them to put it on when they have it, once they’re used to putting on steroids. Then often, they have grade 1, goes back to grade zero, and they’re usually fine with that.