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A CG ctDNA-based prognostic model for predicting OS in mCRPC treated with potent AR inhibition [Video]

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Pediatric Cancer

A CG ctDNA-based prognostic model for predicting OS in mCRPC treated with potent AR inhibition

Susan Halabi, PhD, FSCT, FASA, FASCO, Duke University Medical Center, Durham, NC, discusses the development and validation of a combined clinical and genetic (CG) prognostic model of overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC). This analysis builds upon a previously established clinical model by incorporating circulating tumor DNA (ctDNA) pathogenic genetic alterations (PGAs). Data from the A031201 phase 3 trial, which evaluated enzalutamide with or without abiraterone, were used to develop and validate the CG model. The final model included clinical variables and specific genetic factors such as gains in AR and the AR enhancer, MYC, RSPO2, and losses and/or PGAs in genes like ZBTB16, PTEN, MSH6, and BRCA2, among others. The model showed improved discrimination (tAUC 0.77) compared to the clinical model alone (tAUC 0.72). This CG model can classify patients into prognostic risk groups, aiding in patient selection for future mCRPC trials. This interview took place during the 2024 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.

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