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• W2892066123 abstract "e16019 Background: Advanced UC treatment is being revolutionized by immunotherapy (IT). However, < 30% of patients (pts) will benefit from IT, and additional therapeutic targets are needed. Findings from analyses supporting an investigator-led, AR-based clinical research program are presented. Methods: From 09/2015, we collected the archival tissue blocks from pts who have been treated or consulted at our center and received platinum-based chemotherapy (CT) for MIUC or mUC. Immunohistochemistry (IHC) was performed on 3µm slides using mouse anti-human AR monoclonal Ab (Dako, clone AR441). ≥1% cutoff for AR+ IHC of tumor cells (TC) was used. AR-expressing pts were further stratified as follows: 1-5%, 5-25%, and 25-100%. Univariable (UVA) and multivariable (MVA) Cox models for overall survival (OS) were fitted, the latter adjusted for clinical stage (MIUC vs mUC), presence of visceral metastases, platinum CT type. OS was calculated from the date of first administration of CT. Exploratory PD-L1 co-expression, by TC or stroma (SP142 Ab, 1% cutoff), was analyzed in all pts. Results: 105 pts (46 MIUC and 59 mUC) had their tumor stained. 80 (76.2%) had bladder primary tumor, 85 (80.9%) had pure UC. 59 received cisplatin and 46 carboplatin. Overall, 37 pts (35.2%) had AR-expressing TC, 17 (16.2%) with ≥25% expression. Cox models were built on 93 pts with follow-up duration of ≥6 months. AR-expressing was equally distributed between MIUC and mUC pts (44.4% and 55.6%). On UVA, AR expression was not associated with OS, neither dichotomizing AR+/AR- pts (p = 0.477) nor after accounting for AR-positivity strata (p = 0.845). The same results were confirmed on MVA (p = 0.505 and p = 0.875). In AR+ vs. AR- pts, PD-L1 was equally expressed in the stroma (67.5 vs 57.9%) but less expressed by TC (39.4% vs 52%). Conclusions: AR is frequently expressed on TC of pts with MIUC and mUC, and AR expression does not seem to be associated with OS in these pts. AR pathway is worthy of clinical studies to synergistically act with anti-PD-L1 therapy. AR sequencing and FISH analysis in positive pts is ongoing, and a clinical program of a named-basis administration of antiandrogen therapy has started at our center." @default.
• W2892066123 created "2018-09-27" @default.
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• W2892066123 date "2017-05-20" @default.
• W2892066123 modified "2023-09-26" @default.
• W2892066123 title "Frequent expression of androgen receptor (AR) on tumor cells of muscle-invasive (MIUC) and metastatic urothelial carcinoma (mUC): Insights for clinical research." @default.
• W2892066123 doi "https://doi.org/10.1200/jco.2017.35.15_suppl.e16019" @default.
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