GU Cancers 2026 | HER2 and nectin-4 IHC expression with EV and pembrolizumab

HER2 is an emerging therapeutic target in bladder cancer with ADCs against HER2, Trastuzumab-Deruxtecan. And what we’re really interested in the study was understanding the interplay between HER2 expression and Nectin-4 expression, the target of Enfortumab-Vedotin. The study had two primary goals. One was we wanted to see how HER2 and Nectin-4 expression were integrated in tumors to understand co-expression patterns. And secondly, to understand prognostically the value of HER2 in determining outcomes in the context of the standard first-line approach in the U.S. in Enfortumab-Vedotin plus Pembrolizumab. So the study looked at about 143 patients that had HER2 and Nectin-4 IHC. Two key takeaways from that study. One is that there was some correlation between HER2 and Nectin-4 expression. So if you look at tumors that are HER2 zero, 24% of those tumors also had negative Nectin-4 expression. In contrast, in HER2 2 plus and 3 plus, it was a much smaller percentage of tumors that had negative N4 expression. So it does seem that most tumors have some expression of both markers. The second thing, and I think Enfortumab-Vedotin plus Pembrolizumab is still the standard of care for all comers in the frontline setting. But we really wanted to understand if prognostically, HER2 expression played any value in the context of Enfortumab-Vedotin plus Pembrolizumab. We looked across HER2 expression groups 0, 1+, 2+, and 3+, and there really wasn’t any difference in terms of survival outcomes, progression-free survival, or overall survival. So I think the notion that, you know, HER2 bladder cancers are a more aggressive biology is sort of historical, and we haven’t really seen the same thing in the context of contemporary therapies.

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