Department of Urology, Institute of Urology, Center of Biomedical Big Data and National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu 610041, China.
Curr Oncol. 2023 Dec 4;30(12):10311-10324. doi: 10.3390/curroncol30120751.
Preclinical and clinical studies have suggested potential synergies of combining poly (ADP-ribose) polymerase (PARP) inhibitors and novel hormonal therapies (NHT) for patients with metastatic castration-resistant prostate cancer (mCRPC). We systematically searched PubMed, ClinicalTrials.gov and ASCO-GU annual meeting abstracts up to March 2023 to identify potential phase III trials reporting the use of combining PARP inhibitors with NHT in the first-line setting for mCRPC. A total of four phase III trials met the criteria for subsequent review. Emerging data suggested that the radiographic progression-free survival (rPFS) was significantly longer in the PARP inhibitor combined with NHT group versus the placebo plus NHT group for the first-line setting of biomarker-unselected mCRPC patients, especially for patients with homologous recombination repair (HRR) mutation (HRR m), and with the greatest benefit for BRCA1/2 mutation (BRCA1/2 m) populations. Final overall survival (OS) data of the PROpel trial indicated a significant improvement in median OS for mCRPC patients with HRR m and BRCA1/2 m receiving olaparib + abiraterone. Prior taxane-based chemotherapy might not influence the efficacy of the combination. Compared with the current standard-of-care therapies, combining NHT with PARP inhibitors could achieve a significant survival benefit in the first-line setting for mCRPC patients with HRR and BRCA1/2 mutations.
临床前和临床研究表明，将聚（ADP-核糖）聚合酶（PARP）抑制剂与新型激素疗法（NHT）联合用于转移性去势抵抗性前列腺癌（mCRPC）患者具有潜在协同作用。我们系统地检索了 PubMed、ClinicalTrials.gov 和 ASCO-GU 年会摘要，截至 2023 年 3 月，以确定潜在的 III 期试验，这些试验报告了在 mCRPC 的一线治疗中使用 PARP 抑制剂联合 NHT。共有四项 III 期试验符合后续审查标准。新出现的数据表明，对于生物标志物未选择的 mCRPC 患者的一线治疗，与安慰剂加 NHT 组相比，PARP 抑制剂联合 NHT 组的放射学无进展生存期（rPFS）显著延长，特别是对于同源重组修复（HRR）突变（HRR m）患者，并且 BRCA1/2 突变（BRCA1/2 m）患者获益最大。PROpel 试验的最终总生存期（OS）数据表明，接受奥拉帕利+阿比特龙治疗的 HRR m 和 BRCA1/2 m mCRPC 患者的中位 OS 显著改善。既往紫杉烷类化疗可能不会影响联合治疗的疗效。与当前的标准治疗相比，在 HRR 和 BRCA1/2 突变的 mCRPC 患者的一线治疗中，联合 NHT 与 PARP 抑制剂可实现显著的生存获益。
