GU Cancers 2024 | Correlations between HER2 alterations and PD-L1 expression in bladder cancer
David Aggen, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, NY, gives an overview of findings from a retrospective study exploring the association between HER2 alterations, HER2 and PD-L1 immunohistochemistry (IHC) expression, and clinical outcomes in advanced bladder cancer. An inverse correlation between HER2 IHC expression and PD-L1 combined tumor and immune cell expression score (CPS) was found. Although HER2-mutated tumors were strongly correlated with high-level HER2 IHC expression, discrepancies were noted. Notably, HER2 status was not a prognostic marker for muscle-invasive BC patients. This interview took place at the ASCO GU Cancers Symposium 2024 in San Francisco, CA.
These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.
Transcript (edited for clarity)
HER2 is an emerging therapeutic target, with multiple ADCs targeting this antigen in development, showing promising clinical activity including trastuzumab deruxtecan and disitamab vedotin. We retrospectively analyzed about more than 3000 cases, actually with MSC impact sequencing to look at HER2 ERBB2 mutation alterations, and we found that about 20% of bladder cancers in our cohort from impact had ERBB2 amplification or mutation...
HER2 is an emerging therapeutic target, with multiple ADCs targeting this antigen in development, showing promising clinical activity including trastuzumab deruxtecan and disitamab vedotin. We retrospectively analyzed about more than 3000 cases, actually with MSC impact sequencing to look at HER2 ERBB2 mutation alterations, and we found that about 20% of bladder cancers in our cohort from impact had ERBB2 amplification or mutation. One of the interesting things about that genomic analysis was that ERBB2 and FGFR3 were mutually exclusive in that large patient cohort. We then looked a little more deeply at about 200 patients that that had HER2 IHC done, of which 168 also had PD-L1 immunohistochemistry done to try and understand one, the relationship between next generation sequencing and ERBB2 alterations in HER2 expression, and two the relationship between HER2 and PD-L1. And what we found was striking actually, that about 52% of cancers in our cohort had HER2 2+/3+ expression. We looked at the correlation between HER2 expression and ERBB2 amplification or mutation, and we saw a trend towards an increase in HER2 expression and tumors that had mutations or amplifications in HER2 2+/3+ tumors that was statistically significant. The other thing that we found was really interesting was that HER2 expression by IHC and PD-L1 appeared inversely correlated. If you looked at the HER2 negative tumors, it was about about a PDL and CPA score of 50. In contrast, in HER2 2+/3+it was seven and four respectively. So it does seem that those biomarkers are inversely correlated. You know, and finally, I think one of the things we’re just beginning to explore is HER2 heterogeneity and how the antigen changes within a tumor. The way HER2 scoring is done, HER2 3+ tumor can have 10% of cells that are HER2 three plus or 100% of cells that are HER2 3+, and they’re categorized as the same based on current standards. And so we explored that heterogeneity in a little more detail in the abstract. So you know, I think there’s a few relevant findings from that abstract. One is that there’s a high percentage of tumors in bladder cancer that are ERBB2 altered up to 20%, and perhaps as high as 50% of tumors have HER2 2+/3+ expression. And I think one of the big takeaways is that by NGS alone, you might miss up to 70% of tumors that are HER2 2+/3+ where patients would really benefit, perhaps from another HER2 targeted therapy.
Read more...
