新辅助fuzuloparib联合阿比特龙治疗局部高危前列腺癌（FAST-PC）：一项单组2期研究

IF 14 1区医学 Q1 CELL BIOLOGY Cell Reports Medicine Pub Date : 2025-03-18 Epub Date: 2025-03-07 DOI:10.1016/j.xcrm.2025.102018

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

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引用次数: 0

摘要

临床前研究表明雄激素受体抑制剂和聚二磷酸腺苷核糖聚合酶（PARP）抑制剂之间具有协同作用。这项2期试验（NCT05223582）评估了新辅助fuzuloparib +阿比特龙在35例未接受治疗的局限性高危前列腺癌患者中的疗效。患者接受六个周期的治疗，然后进行根治性前列腺切除术。主要终点是病理完全缓解（pCR）和最小残留病（MRD,≤5mm）。pCR/MRD联合率为46%(95%可信区间[CI]: 29%-63%)， 2年无生化进展生存率为53%。23%的患者发生≥3级不良事件。双等位基因同源重组修复/BRCA2改变与更快的前列腺特异性抗原下降相关。治疗后的基因组分析显示MYC扩增和增殖标记降低，上皮-间充质转化/激活蛋白1 （AP-1）通路激活。该试验达到了主要终点，证明了可行性和初步疗效，而探索性生物标志物可能指导未来的研究。

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Neoadjuvant fuzuloparib combined with abiraterone for localized high-risk prostate cancer (FAST-PC): A single-arm phase 2 study.

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.

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来源期刊

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.