Efficacy and safety of organoid-based drug sensitivity screening to guide the treatment of mCRPC patients progressed after first-line treatment.

TPS278 Background: Treatment for metastatic castration-resistant prostate cancer (mCRPC) patients progress after first-line therapy remains challenging due to limited options and heterogeneous response. Organoid-based drug sensitivity screening offers an innovative approach by simulating the tumor microenvironment in vitro, potentially allowing for personalized treatment strategies based on individual tumor responses to various drugs. This study aims to assess the efficacy and safety of using organoid-based drug sensitivity screening to guide treatment decisions in mCRPC patients. Methods: This is a prospective, open-label, single-arm observational study designed to recruit 30 mCRPC patients with bone metastases who have progressed after first-line therapy. Residual tissue from biopsies of bone metastatic lesions will be used to culture organoids for drug sensitivity screening. Screening regimens include at least Olaparib, Docetaxel or platinum-based chemotherapy, and Abiraterone plus Niraparib, as recommended by current guidelines. Additionally, 141 other drugs from a previously established library are available for screening, based on investigator and patient preferences. The treatment regimen will be selected based on the agent that demonstrates the highest sensitivity in the screening process. The primary endpoint is PSA response rate, defined as a 50% decrease in PSA levels from baseline. Secondary endpoints include radiologic progression-free survival (rPFS), objective response rate (ORR), duration of response (DOR), and overall survival (OS). Patient recruitment is ongoing at Sun Yat-sen University Cancer Center, with 5 patients (5/30, 16.7%) enrolled as of September 3, 2024. Data analysis is expected to begin in 2025, following the completion of recruitment. Clinical trial information: NCT06529549 .