BackgroundUrothelial carcinoma (UC) is a common malignancy with significant associated mortality. Recent clinical trials suggest an emerging role for HER2-targeted therapy. Testing for HER2 expression in UC is not part of current routine clinical practice. In consequence, the prevalence of HER2 expression in UC is not well defined.MethodsA systematic literature review (SLR) was conducted to characterize HER2 expression in both locally advanced unresectable or metastatic (LA/mUC) and earlier stage UC, classified as HER2+, HER2-low, HER2-. HER2+ was defined as an immunohistochemistry (IHC) score of 3+ or IHC 2+ and ISH/FISH+. HER2-low was defined as an IHC score of 2+ and ISH/FISH- or IHC 1+. HER2- was defined as an IHC score of 0. Weighted averages were calculated to generate an estimate of the population prevalence.ResultsA total of 88 studies were identified, with 45, 30, and 13 studies investigating LA/mUC, earlier stage UC, and mixed stage/unspecified, respectively. The most common assays used were Dako HercepTest and Ventana Pathway anti-HER2/neu (4B5) for IHC to assess HER2 protein expression; Abbott PathVysion HER-2 DNA Probe Kit, FoundationOne CDx, and Guardant360 CDx for assessing HER2 gene amplification. The most frequently cited scoring guidelines were ASCO/CAP guidelines for breast cancer and gastric cancer, though most studies defined their own criteria for HER2 expression. Using the pre-specified definition, HER2+ prevalence ranged from 6.7% to 37.5% with a weighted average of 13.0% in LA/mUC. Only 1 study presented data that could be classified as HER2+ based on pre-specified criteria in earlier stage UC patients, and this study represented a likely outlier, at 76.0%.ConclusionThe results from this SLR help to shed light on HER2 expression in UC, a potentially clinically relevant biomarker-driven subpopulation for emerging HER2-directed regimens. Results of this SLR illuminate the variability in how HER2+ status expression levels are being assessed and how HER2+ is defined. Consensus on standardized HER2 testing and scoring criteria is paramount to better understand the clinical relevance in patients with UC.
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