Gynecology Division, Department of Medical and Surgical Sciences and Translational Medicine, Sant'Andrea University Hospital, Sapienza University of Rome, Via di Grottarossa 1035, 00189 Rome, Italy; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Gynaecology, European Competence Center for Ovarian Cancer, Campus Virchow Clinic, 13353 Berlin, Germany; Laboratory of Tumor Immunology and Cell Therapy Unit, Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.
Gynecology Division, Department of Medical and Surgical Sciences and Translational Medicine, Sant'Andrea University Hospital, Sapienza University of Rome, Via di Grottarossa 1035, 00189 Rome, Italy.
Cancer Treat Rev. 2020 Jul;87:102040. doi: 10.1016/j.ctrv.2020.102040. Epub 2020 May 26.
The second decade of 2000s is witnessing a new ovarian cancer (OC) paradigm shift thanks to the results recently obtained by a new class of targeted agents: the Poly(ADP-ribose)polymerase (PARP)-Inhibitors (PARPi). Aim of this meta-analysis is to analyze available results obtained with PARPi, administered alone or in combination with chemo- and/or target-therapies in terms of efficacy and safety for the treatment of recurrent and primary advanced OC.
On December 2019, all published phase II/III randomized clinical studies were systematically searched using the terms "[Parp-Inhibitor] AND [ovar*]". Twelve phase II/III randomized controlled trials were identified, with a total number of 5171 patients included.
Results demonstrated that PARPi account for a significant improvement of PFS in both recurrent and primary OC setting, independently from their administration schedule and independently from patients' BRCA mutational status. Moreover, patients harboring a Homologous Recombination Deficiency (HRD) positive testing primary or recurrent OC progress significantly later after PARPi administration/association. Results also reported that PARPi increase the occurrence of severe (G3-G4) anemia. Furthermore, severe fatigue occurred more frequently among patients subjected to PARPi combined with chemotherapy and to PARPi plus Bevacizumab. Finally, a significant increase in severe high blood pressure occurrence was observed when PARPi was added to antiangiogenetics, compared to PARPi alone but a significant decrease in G3-G4 hypertension occurrence was found in PARPi plus bevacizumab users compared to Bevacizumab alone.
PARPi are a valid option for the treatment of both primary and relapsed OC patients, with a relative low incidence of severe side effects.
由于最近一类靶向药物——聚（ADP-核糖）聚合酶（PARP）抑制剂（PARPi）的研究结果，21 世纪 20 年代见证了卵巢癌（OC）的新范式转变。本荟萃分析旨在分析单独或联合化疗和/或靶向治疗使用 PARPi 治疗复发性和原发性晚期 OC 的疗效和安全性。
2019 年 12 月，系统地使用术语“[PARP 抑制剂]和[卵巢]”搜索了所有已发表的 II/III 期随机临床试验。确定了 12 项 II/III 期随机对照试验，共纳入 5171 例患者。
结果表明，PARPi 在复发性和原发性 OC 环境中均显著改善了无进展生存期（PFS），这与给药方案和患者 BRCA 突变状态无关。此外，同源重组缺陷（HRD）阳性检测的原发性或复发性 OC 患者在接受 PARPi 给药/联合治疗后进展明显延迟。结果还报告称，PARPi 增加了严重（G3-G4）贫血的发生。此外，PARPi 联合化疗和 PARPi 联合贝伐珠单抗的患者更容易出现严重疲劳。与单独使用 PARPi 相比，当 PARPi 联合抗血管生成药物时，严重高血压的发生率显著增加，但与单独使用贝伐珠单抗相比，PARPi 联合贝伐珠单抗的患者中严重高血压的发生率显著降低。
PARPi 是治疗原发性和复发性 OC 患者的有效选择，严重不良反应发生率相对较低。
