Trastuzumab Deruxtecan Plus Nivolumab Among Patients With HER2-Expressing Urothelial Carcinoma
Dr. Gong: Hello, everyone. Welcome to PracticeUpdate. My name is Jun Gong, and I'm a practicing GU medical oncologist at Cedars-Sinai Medical Center. It is my absolute honor to interview one of the key opinion leaders in GU Oncology, Dr. Monty Pal. Welcome to PracticeUpdate.
Dr. Pal: It's great to be here working with you again.
Dr. Gong: So ASCO GU 2022 happened, and it was a very exciting sessions and conference. One of the abstracts actually touched on a novel combination in urothelial carcinoma, specifically trastuzumab deruxtecan plus nivolumab in patients with HER2 expressing UC. I wanted to talk to you about what do you think about the targetability of HER2 alterations in UC?
Dr. Pal: Yeah, it's a great question. I don't know if we ever talked about this, Jun, but I grew up in a HER2 breast cancer laboratory at UCLA. I worked with Mark Pegram who then was working under the direction of Dennis Slamon, and I was actually first exposed to looking at HER2 expression of breast cancer cell lines. Urothelial cancer does express in a proportion of individuals HER2 at higher levels. I will say that much like gastric cancer, I think the pattern of expression is a little spottier as opposed to what you see in the context of breast cancer where it's fairly consistent. But I think it's a very reasonable target.
Dr. Gong: Great to hear that. And so I wanted to ask you what was the design of this trial and the key findings?
Dr. Pal: Yeah. So this was a phase I/II study. It actually looked separately at patients' outcomes on the basis of the IHC level of HER2 expression, either 1+ which was deemed low expression or higher expression at 2+ and 3+. Ultimately, what they identified is that if you had higher expression of HER2, response rates were marginally elevated. You could see response rate in the high expressing cohort of 37%, which I thought was quite good. There's a complete response rate of 13%. So I really think this data has legs. I definitely think that the activity is probably going to be more robust amongst those individuals who have higher levels of expression. But I will say that the study really did fail to accrue to some extent in lower levels of expression, only four patients within the cohort there.
Dr. Gong: Those are some great points. So we only have a few biomarkers that drive therapy in bladder cancer, PDL1 in select populations, FGFR alterations. Do you think HER2 with this data could eventually be a third biomarker for UC?
Dr. Pal: I think it's reasonable. I'd love to see how the data pans out. You have so many effective HER2-directed therapies now being applied in breast cancer. I'm hard-pressed to think that if we don't find the right biomarker, we won't be able to apply it in bladder cancer. Right now, of course, it's a theoretical conversation, but it's still a good one to have.
Dr. Gong: Thank you for your expert insight, Dr. Pal.
Dr. Pal: Thank you, Jun.
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