Predictive and prognostic biomarker identification in a large cohort of androgen receptor-positive salivary duct carcinoma patients scheduled for combined androgen blockade.

6071 Background: Patients suffering from recurrent or metastatic (R/M) salivary duct carcinoma (SDC) are often treated with combined androgen blockade (CAB). This treatment however frequently fails (response rates: 18-53%), resulting in a worse prognosis. Therefore, biomarkers that have prognostic value and can predict response urgently needed. Methods: mRNA 77 R/M receptor (AR) positive SDC patients leuprorelin acetate bicalutamide was extracted pre-treatment tumor specimens. AR, Notch, Mitogen-Activated Protein Kinase (MAPK), Transforming Growth Factor beta (TGFβ), Estrogen Receptor (ER), Hedgehog (HH) the Phosphoinositide 3-Kinase (PI3K) signaling pathway activities were calculated based on expression levels of relevant target genes. Besides this, 5-alpha reductase type 1 ( SRD5A1) Human Epidermal growth factor 2 (HER2) status determined. Clinical benefit defined as complete partial stable disease ≥6 months. Results: Of 7 pathways, AR activity best predictor clinical (AUC 0.67, 95%-CI 0.54-0.80). At threshold 47.8, 21% tested negative, negative predictive 93%. SRD5A1 outperformed pathways regarding 0.78, 0.67-0.88). Fitting multivariable model led to identification SRD5A1, Notch TGFβ most combination 0.82, 0.72-0.91). HH also importance progression free survival for overall (median 175.0 weeks high versus 96.7 low expression). Conclusions: Our study revealed and/or HH, CAB. be used identifying non-responders. Further validation is required before implementation these practice. The observed role CAB forms rational basis including SRD5A1-inhibitors patients.[Table: see text]