Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA, USA.
Division of Gynecologic Oncology, Dana-Farber Cancer Institute , Boston, MA, USA.
Expert Opin Emerg Drugs. 2020 Jun;25(2):165-188. doi: 10.1080/14728214.2020.1773791. Epub 2020 Jun 22.
Poly (ADP-ribose) polymerase (PARP) inhibitors have demonstrated significant anticancer activity in cancers harboring homologous recombination deficiency (HRD), exemplified by high grade serous ovarian cancer (HGSC). PARP inhibitors (PARPi) are being used in women with newly diagnosed ovarian cancer as well as in the recurrent setting. PARPi combination therapies are in development.
This review discusses the treatment of ovarian cancer, key PARPi clinical trials, mechanisms of action of PARPi, and novel PARPi combination regimens under investigation. PubMed and ClinicalTrials.gov were searched for PARPi trials. Active development was confirmed via PharmaProjects.
PARPi have shown to improve progression-free survival (PFS) for women with HGSC as monotherapy in both frontline and recurrent maintenance settings and as monotherapy as treatment for recurrence. These benefits are greatest in HGSC with underlying HRD, in particular for those with deleterious mutations, and with the least benefit in cancers that are HR proficient (HRP) and BRCA wild-type (wt). Thus far, an improvement in overall survival has only been demonstrated in patients with mutated EOC treated with olaparib maintenance in the platinum sensitive recurrence setting. Novel combinations of PARPi are undergoing testing in an effort to increase PARPi efficacy in HRP or PARPi-resistant cancers.
聚（ADP-核糖）聚合酶（PARP）抑制剂在同源重组缺陷（HRD）的癌症中表现出显著的抗癌活性，高级别浆液性卵巢癌（HGSC）就是一个典型例子。PARP 抑制剂（PARPi）不仅在新诊断的卵巢癌患者中得到应用，在复发患者中也得到应用。PARPi 联合治疗方案正在开发中。
本文讨论了卵巢癌的治疗方法、关键的 PARPi 临床试验、PARPi 的作用机制，以及正在研究的新型 PARPi 联合方案。通过 PubMed 和 ClinicalTrials.gov 搜索了 PARPi 试验。通过 PharmaProjects 确认了正在进行的开发。
PARPi 作为单药在一线和复发维持治疗中，以及作为复发治疗的单药，已显示出可改善 HGSC 患者的无进展生存期（PFS）。这些益处对于具有潜在 HRD 的 HGSC 最大，特别是对于那些具有有害突变的患者，而对于 HR 功能正常（HRP）和 BRCA 野生型（wt）的癌症则益处最小。迄今为止，仅在铂类敏感复发环境中接受奥拉帕利维持治疗的 突变型 EOC 患者中观察到总生存期的改善。正在对 PARPi 的新型联合方案进行测试，以提高 PARPi 在 HRP 或 PARPi 耐药性癌症中的疗效。
