Clinical Utility of Olaparib in the Treatment of Metastatic Castration-Resistant Prostate Cancer: A Review of Current Evidence and Patient Selection.
Clinical Utility of Olaparib in the Treatment of Metastatic Castration-Resistant Prostate Cancer: A Review of Current Evidence and Patient Selection.
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DOI：
10.2147/ott.s315170
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发表时间：
2021
影响因子：
4
通讯作者：
Gong J
中科院分区：
文献类型：
--
作者：
LeVee A;Lin CY;Posadas E;Figlin R;Bhowmick NA;Di Vizio D;Ellis L;Rosser CJ;Freeman MR;Theodorescu D;Freedland SJ;Gong J
转移性去势抵抗性前列腺癌（mCRPC）是一种侵袭性和致命性疾病，中位生存期为36个月。随着基因测序的出现，以确定个体基因组谱和获得性肿瘤特异性通路，靶向治疗彻底改变了癌症治疗，包括mCRPC的治疗策略。聚（腺苷5 α-二磷酸）核糖聚合酶抑制剂（PARPi）是一种口服药物，靶向同源重组修复（HRR）途径中的突变，在大约27%的前列腺癌患者中发现。于二零二零年五月，首个PARP抑制剂奥拉帕尼获美国食品药品监督管理局批准用于患有HHR基因突变的mCRPC男性，其基于III期PROfound试验的结果，该试验显示接受奥拉帕尼且其疾病在新型激素药物治疗后进展的mCRPC男性的总生存期有所改善。本综述总结了奥拉帕尼治疗男性mCRPC的现有证据和临床效用。我们描述了PARPi的作用机制，奥拉帕尼在mCRPC男性中的关键临床试验，以及正在进行的II期和III期临床试验，研究奥拉帕尼在mCRPC中的联合治疗和一线治疗。
Metastatic castration-resistant prostate cancer (mCRPC) is an aggressive and fatal disease with a median survival of 36 months. With the advent of genetic sequencing to identify individual genomic profiles and acquired tumor-specific pathways, targeted therapies have revolutionized cancer treatment, including the treatment strategy in mCRPC. Poly(adenosine 5ʹ-diphosphate) ribose polymerase inhibitors (PARPi) are oral drugs that target mutations in the homologous recombination repair (HRR) pathway, which are found in approximately 27% of prostate cancer patients. In May 2020, the first PARP inhibitor, olaparib, was approved by the US Food and Drug Administration for men with mCRPC with HHR gene mutations based on the findings of the Phase III PROfound trial that showed improved overall survival in men with mCRPC who received olaparib and whose disease had progressed on a novel hormonal agent. This review summarizes the current evidence and clinical utility of olaparib as treatment in men with mCRPC. We describe the mechanism of action of PARPi, key clinical trials of olaparib in men with mCRPC, and ongoing Phase II and III clinical trials investigating olaparib in combination therapy and as front-line therapy in mCRPC.