Abstract 1015: Real-world evaluation of androgen receptor (AR) ligand-binding domain (LBD) mutations in Chinese patients with metastatic castration-resistant prostate cancer (mCRPC)

Abstract Purpose: While AR LBD mutations have been extensively studied in Caucasian populations, there is a lack of research in Chinese populations. This study aimed to investigate the prevalence of AR LBD activated mutations in Chinese mCRPC patients using real-world databases. Methods: This observational study analyzed two databases of Chinese mCRPC patients. The Gloriousmed database included 2, 030 patients with circulating-tumor DNA (ctDNA) collected between 2016-2023 and tested using Gloriousmed’s Pushengtai (86 genes) /Qianxianan panel (693 genes), while the Geneseeq database included 91 patients with tissue and/or ctDNA collected between 2020-2022 and tested using Geneseeq Prime panel (425 genes). Activated AR LBD mutation and other prostate driver mutations were assessed in patients with novel hormonal agents (NHA) treatment information. Results: In Gloriousmed’s ctDNA database, 633 (31.2%) were NHA-naïve (not received any NHA treatment), and 1, 397 (68.8%) were NHA-treated (undergone NHA treatment before sample collection). The prevalence of AR LBD mutations in NHA-treated patients (20.5%, 287/1397) was significantly higher than that in NHA-naïve patients (15.2%, 96/633) (Fisher test P=0.004). Regarding specific activated point mutations in the AR LBD, W742C (7.74%) and W742L (6.32%) were the two most common mutations in NHA-naïve populations, and significantly higher prevalence of L702H (5.44% vs 2.37%) and T878A (9.45% vs 3.48%) mutations were found in NHA-treated patients compared to NHA-naïve patients (Fisher test P<0.01).. In Geneseeq database, 21 (23.1%) subjects were NHA-naïve, while 70 (76.9%) were NHA-treated. The prevalence of AR LBD mutations in ctDNA was numerically higher in NHA-treated (21.3%, 13/61) than in NHA-naïve patients (5%, 1/20) (Fisher test P=0.17). Notably, the prevalence of AR LBD mutations in ctDNA was significantly higher than that in tissue (14/81 vs. 3/57, Fisher test P=0.04). Conclusions: This study found consistent prevalence of AR LBD activated mutations (20.5% and 21.3%) in ctDNA from Chinese mCRPC patients after NHA treatment using two real-world datasets. Higher prevalence of AR LBD mutations was observed in NHA-treated patients compared to NHA-naïve patients and in ctDNA compared to tissue samples. Different patterns of specific AR LBD mutations were also identified in NHA-naïve and NHA-treated patients. These findings provide valuable insights into the overall prevalence of AR LBD mutations, as well as specific point mutations frequency that potentially associated with different treatment in real-world datasets of Chinese mCRPC patients. Citation Format: Yufei Chen, Bingjie Dong, Dapeng Li, Yinglong Xiao, Julia Markensohn, E.J. Dettman, Carol Pena, Xiaoqiao Liu. Real-world evaluation of androgen receptor (AR) ligand-binding domain (LBD) mutations in Chinese patients with metastatic castration-resistant prostate cancer (mCRPC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1015.