Fuzuloparib combined with abiraterone in the neoadjuvant treatment of localised high-risk prostate cancer (FAST-PC): A single-arm phase II study

BackgroundIn neoadjuvant therapy for localized high-risk prostate cancer (PCa), androgen receptor signaling inhibitors (ARSi) yielded suboptimal major pathological responses (<30%). Preclinical research suggested synergy between ARSi and poly (ADP-ribose) polymerase inhibitors (PARPi). The FAST-PC trial (NCT05223582) evaluated the efficacy and safety of combining fuzuloparib with abiraterone in this context.MethodsTreatment-naive men with NCCN high-/very high-risk PCa were recruited. All patients received fuzuloparib, abiraterone, prednisone, and medical castration of each 28- day cycle for six cycles, followed by radical prostatectomy (RP). Primary endpoints were pathological complete response (pCR) or minimal residual disease (MRD) (≤5mm), with key secondary endpoints including PSA responses, biochemical progression-free survival (bPFS), and safety. Molecular analyses of pre- and post-treatment specimens were conducted.ResultsBetween June 2021 and November 2022, 35 eligible patients received at least one study drug. Three patients achieved pCR, and 13 achieved MRD, resulting in a pCR/MRD rate of 45.7% (95%CI: 28.8%-63.4%) in the intention-to-treat population. Median postoperative follow-up time was 19.7 months. Patients achieving pCR/MRD had longer median bPFS (Not reached vs. 10.8 months, p =0.046). Grade ≥3 treatment-related adverse events were observed in six patients (17.1%), including myelodysplastic syndrome and grade 4 drug-induced liver injury in one patient each. Grade 3 anemia occurred in three patients (8.6%) without requiring transfusion. Molecular analysis of pre- and post-treatment specimens is ongoing.ConclusionsThe FAST-PC trial, exploring the combination of PARPi and ARSi in the neoadjuvant management of localized high-risk PCa, demonstrated a significant 45.7% pCR/MRD rate, while maintaining a safety profile consistent with the individual agents involved. Molecular analysis of pre- and post-treatment specimens is ongoing.Clinical trial identificationNCT05223582.Legal entity responsible for the studyYao Zhu.FundingThis study is supported by the National Nature Science Foundation of China (82172621, 81972375), Shanghai Medical Innovation Research Special Project (21Y11904300), the General Program of Beijing Xisike Clinical Oncology Research Foundation (Y-MSDZD2021-0230, Y-2019AZMS-0012), Chinese Anti-Cancer Association-Hengrui PARP Inhibitor Tumor Research Fund (Phase I), Bethune Urology Tumor Special Research Fund (mnzl202004), Program of Shanghai Academic Research Leader (23XD1420600), Oriental Scholar Professorship (TP2022051), and Shanghai Shenkang Research Physician Innovation and Transformation Ability Training Project (SHDC2022CRD035).DisclosureAll authors have declared no conflicts of interest.