Roberts Hayley Nicole, Maurice-Dror Corinne, Chi Kim Nguyen
Department of Medical Oncology, BC Cancer Agency, Vancouver, Canada.
Department of Medicine, University of British Columbia, Vancouver, Canada.
Future Oncol. 2025 Jan;21(2):201-211. doi: 10.1080/14796694.2024.2442900. Epub 2024 Dec 23.
Metastatic prostate cancer remains incurable. Though significant progress has been made in the field, the search for agents that improve outcomes for patients is ongoing. Several clinical trials have explored the benefit of combining PARP inhibitors (PARPi) with androgen receptor pathway inhibitors (ARPIs) for metastatic castrate resistant prostate cancer (mCRPC), especially those cancers with alterations in homologous recombination repair (HRR) genes. Niraparib, a highly selective inhibitor of PARP1 and PARP2, has been shown to confer a radiographic progression-free survival benefit in the treatment of mCRPC with HRR-associated gene alterations, particularly and (), when combined with abiraterone acetate plus prednisolone (AAP). This combination has recently been approved in the USA, Canada and Europe for patients with mCRPC and a gene mutation. This review summarizes the evidence with regards to the pharmacologic activity and clinical efficacy of niraparib with a specific focus on its efficacy in combination with AAP in mCRPC patients with HRR alterations.
转移性前列腺癌仍然无法治愈。尽管该领域已取得重大进展，但仍在继续寻找能够改善患者预后的药物。多项临床试验探讨了将聚（ADP-核糖）聚合酶抑制剂（PARPi）与雄激素受体通路抑制剂（ARPI）联合用于转移性去势抵抗性前列腺癌（mCRPC）的益处，尤其是那些同源重组修复（HRR）基因发生改变的癌症。尼拉帕利是一种高度选择性的PARP1和PARP2抑制剂，已证明在与醋酸阿比特龙加泼尼松龙（AAP）联合使用时，对治疗具有HRR相关基因改变的mCRPC具有影像学无进展生存获益，特别是 和 （）。这种联合用药最近在美国、加拿大和欧洲已被批准用于患有mCRPC和 基因突变的患者。本综述总结了关于尼拉帕利药理活性和临床疗效的证据，特别关注其与AAP联合用于具有HRR改变的mCRPC患者的疗效。
