Impact of different HER2 expression levels on the outcomes of second-line immunotherapy for metastatic urothelial carcinoma.

Abstract

524 Background: Immunotherapy has become an option of second-line treatment for metastatic urothelial carcinoma (mUC) after the failure of platinum-containing chemotherapy. HER2 expression is an adverse prognostic factor of urothelial carcinoma (UC) while the predictive value of HER2 expression in UC treatment remains unknown. This study attempts to explore the impact of different HER2 expression and gene amplification levels on the outcomes of second-line immunotherapy in metastatic UC. Methods: The baseline clinical data and the outcomes after second-line anti-PD-1 immunotherapy from 2017 to 2021 in 79 patients with metastatic UC who failed to the first-line platinum-containing chemotherapy were reviewed. The expression level of HER2 was detected by immunohistochemistry (IHC) staining ( Anti-Her2/neu, Cat.4B5, Ventana ) from formalin-fixed paraffin-embedded (FFPE) tumor tissue of patients. The copy number amplification level of HER2 gene was detected by second-generation sequencing (NGS) from FFPE tumor tissue of patients. The correlation between HER2 expression and objective response rate (ORR), median progression-free survival (PFS) and overall survival (OS) were analyzed. Results: HER2 expression levels by IHC were performed in 77 patients and the copy number (CN) amplification level of 20 patients with HER2 IHC 2+ were detected by NGS. The median PFS of HER2 negative (IHC 0), low expression (IHC 2 +/ CN - and IHC 1 +) and overexpression (IHC 3 + and IHC 2 +/ CN +) patients were 11.0 months (95% confidence interval [CI]: 1.4-20.6 months), 3.7 months (95% CI: 1.3-6.1 months) and 1.8 months (95% CI: 0.8-2.8 months), respectively, with significant difference in the overall comparison ( P = 0.001) and in the each two comparisons. ORR had a trend to decrease gradually with the increase of HER2 expression level from negative to overexpression (42.4% vs. 31.6% vs. 0%, P = 0.08). However, no correlation between HER2 expression and OS after anti-PD-1 immunotherapy was observed. Conclusions: Different HER2 expression levels have a significant impact on the PFS of the second-line anti-PD-1 immunotherapy in patients with metastatic urothelial carcinoma. The overexpression of HER2 (IHC 3 + and IHC 2 +/ CN +) may be an adverse factor, while the HER2-negative status may be a favorable factor. HER2 expression have potential value in predicting the efficacy of second-line immunotherapy for advanced urothelial carcinoma, which needs further research.