(UroToday.com) The 2024 GU ASCO annual meeting featured a urothelial carcinoma rapid oral abstract session, including a presentation by Dr. David Aggen discussing outcomes of HER2 and PD-L1 immunohistochemistry expression, and HER2 genomic alterations in advanced bladder cancer.
Novel antibody drug conjugates targeting HER2 have shown promising activity in advanced urothelial carcinoma as monotherapy and in combination with checkpoint blockade. ERBB2 is frequently altered (mutated or amplified) in 12%-30% of bladder tumors, and the prevalence of HER2 overexpression in urothelial carcinoma has ranged from 7-38% across different series. As such, the aims of this study were to:
- Define the prevalence of ERBB2 alterations in urothelial carcinoma and the association with HER2 expression by immunohistochemistry
- Understand the heterogeneity of HER2 expression and the relationship between HER2 and PD-L1 expression
This study retrospectively analyzed bladder cancer samples for PD-L1 and HER2 immunohistochemistry expression and compared HER2 alterations from genomic profiling with the MSK IMPACT platform. HER2 immunohistochemistry expression was defined as 0, 1+, 2+, 3+, and PD-L1 immunohistochemistry was the combined tumor and immune cell PD-L1 expression score (CPS). HER2 alteration was defined as either pathogenic mutation and/or amplification. Dr. Aggen and colleagues studied pairwise associations between HER2 alteration, PD-L1, and HER2 immunohistochemistry expression in all patients and their associations with progression-free survival and overall survival for muscle-invasive bladder cancer patients. Association analyses were performed using the Wilcoxon rank-sum test or Fisher’s exact test, and Kaplan-Meier method and Cox proportional hazard models were used for time-to-event analyses.
Among 202 patients with HER2 immunohistochemistry, 188 had MSK IMPACT, and 168 had PD-L1 CPS. The baseline characteristics for these patients are as follows:
The overall incidence of HER2 alteration was 22.3%, 48.2% had CPS ³10, and HER2 immunohistochemistry distribution was:
- 0: 18.8%
- 1+: 29.7%
- 2+: 33.7%
- 3+: 17.8%
ERBB2 and FGFR3 alterations were noted to be mutually exclusive:
The CPS score was inversely associated with HER2 immunohistochemistry expression (p < 0.001), and there was no association noted between CPS score and HER2 alteration (p = 0.735). HER2 altered tumors were strongly correlated with high-level HER2 immunohistochemistry expression (p<0.001). However, 41% (n = 14 of 34) of HER2 immunohistochemistry 3+ samples did not have HER2 alterations, and 17% (n = 7 of 36) of HER2 altered samples had HER2 immunohistochemistry expression of 0:
In patients with muscle-invasive bladder cancer, HER2 alteration and HER2 immunohistochemistry expression (0/1+ vs. 2+/3+) were not associated with progression-free survival (p = 0.5 and p = 0.4, respectively) or overall survival (p = 0.84 and p = 0.94, respectively):
A higher PD-L1 CPS score (>=10 vs <10) was associated with improved progression-free survival for muscle-invasive bladder cancer patients (p = 0.03).
Dr. Aggen concluded his presentation discussing outcomes of HER2 and PD-L1 immunohistochemistry expression, and HER2 genomic alterations in advanced bladder cancer with the following take-home points:
- ERBB2 alterations (mutations and/or amplifications) were identified by MSK IMPACT in ~20% of urothelial cancers
- In this cohort, HER2 2+ or 3+ expression was present in 52% of tumors. NGS alone may not capture patients who would potentially benefit from HER2-directed therapy. HER2 expression heterogeneity by immunohistochemistry was observed in a significant number of tumors
- PD-L1 and HER2 expression are inversely correlated in this cohort
- These data support the further investigation of HER2-targeted agents and underscore the need for standardization of HER2 expression assessment by immunohistochemistry in patients with advanced urothelial carcinoma
Presented by: David H. Aggen, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, NY
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Jan 25 – Sat, Jan 27, 2024.