Preclinical studies suggest synergistic effects between androgen receptor inhibitors and poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors. This phase 2 trial (NCT05223582) evaluates neoadjuvant fuzuloparib plus abiraterone in 35 treatment-naive men with localized high-risk prostate cancer. Patients receive six cycles of therapy followed by radical prostatectomy. Primary endpoints are pathological complete response (pCR) and minimal residual disease (MRD, ≤5 mm). The combined pCR/MRD rate is 46% (95% confidence interval [CI]: 29%-63%), with a 53% 2-year biochemical progression-free survival rate. Grade ≥3 adverse events occur in 23% of patients. Biallelic homologous recombination repair/BRCA2 alterations correlate with faster prostate-specific antigen decline. Post-treatment genomic analyses reveal reduced MYC amplification and proliferation markers, alongside activated epithelial-mesenchymal transition/activator protein 1 (AP-1) pathways. The trial meets its primary endpoint, demonstrating feasibility and preliminary efficacy, while exploratory biomarkers may guide future studies.
Cell reports. Medicine. 2025 Mar 05 [Epub ahead of print]
Tingwei Zhang, Beihe Wang, Yu Wei, Hualei Gan, Bangwei Fang, Xiaomeng Li, Junlong Wu, Xiaojie Bian, Jianfei Wang, Stephen J Freedland, Shenglin Huang, Dingwei Ye, Yao Zhu
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Genitourinary Cancer Institute, Shanghai, China., Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China., Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China., Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Urology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Section of Urology, Durham VA Medical Center, Durham, NC, USA., Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Department of Medical Oncology, Fudan University Shanghai Cancer Center, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai, China. Electronic address: ., Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Genitourinary Cancer Institute, Shanghai, China. Electronic address: ., Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Genitourinary Cancer Institute, Shanghai, China. Electronic address: .