Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-sen University, Zhongshan Second Road 58, Guangzhou 510080, Guangdong, P. R. China.
School of Chemical Biology and Biotechnology, State Key Laboratory of Chemical Oncogenomics, Peking University Shenzhen Graduate School, Shenzhen, China, 518055.
Biosci Rep. 2020 Mar 27;40(3). doi: 10.1042/BSR20192226.
Poly ADP ribose polymerase (PARP) inhibitors can effectively kill cancer cells by restraining the activity of DNA repair enzymes and utilizing the characteristics of BRCA mutations. This article evaluates the efficacy and safety of PARP inhibitors (PARPis) in the maintenance treatment of ovarian cancer.
We searched for clinical trials in electronic databases. PARPis efficacy were evaluated by the hazard ratios (HR) and its 95% confidence intervals (95% CI) of overall survival (OS) and progression-free survival (PFS) between the PARPis groups and placebo groups, while the PARPis' safety was assessed by relative risk (RR) values of adverse events (AEs) between the two arms.
The immature OS data manifested that patients with BRCA mutation receiving PARPis therapy versus placebo therapy appeared to have longer OS (HR = 0.78, 95%CI = 0.61-1.01; P = 0.06). Compared with placebo group, PARP group had a significant advantage in PFS in ovarian cancer patients with BRCA wild-type (BRCAwt), BRCA mutation (BRCAm), BRCA status unclassified, BRCA1 mutation subgroup and the BRCA2 mutation subgroup (BRCAwt: HR = 0.53, 95%CI = 0.42-0.68, P < 0.00001; BRCAm: HR = 0.30, 95%CI = 0.26-0.34, P < 0.00001; BRCA status unclassified: HR = 0.52, 95%CI = 0.41-0.66, P < 0.00001; BRCA1m: HR = 0.38, 95%CI = 0.29-0.48, P < 0.00001; BRCA2m: HR = 0.23, 95%CI = 0.10-0.57, P = 0.001). Our analysis revealed the incidence rates for AEs of grade ≥3 (grades 3 to 4) and serious AEs in PARPis group were 55.19% and 26.29%, respectively.
Our meta-analysis demonstrates that PARPis therapy can significantly improve PFS in ovarian cancer patients, but it has no benefit in OS. However, the therapy is associated with a significant increase in the risk of AEs of grade ≥ 3 and serious AEs.
多聚 ADP 核糖聚合酶（PARP）抑制剂可通过抑制 DNA 修复酶的活性并利用 BRCA 突变的特征，有效杀死癌细胞。本文评估了 PARP 抑制剂（PARPi）在卵巢癌维持治疗中的疗效和安全性。
我们在电子数据库中检索了临床试验。通过 PARPi 组与安慰剂组之间总生存期（OS）和无进展生存期（PFS）的风险比（HR）及其 95%置信区间（95%CI）评估 PARPi 的疗效，而 PARPi 的安全性则通过两组之间不良反应（AE）的相对风险（RR）值来评估。
不成熟的 OS 数据表明，接受 PARPi 治疗的 BRCA 突变患者与接受安慰剂治疗的患者相比，OS 似乎更长（HR=0.78，95%CI=0.61-1.01；P=0.06）。与安慰剂组相比，PARP 组在 BRCA 野生型（BRCAwt）、BRCA 突变（BRCAm）、BRCA 状态未分类、BRCA1 突变亚组和 BRCA2 突变亚组的卵巢癌患者中 PFS 具有显著优势（BRCAwt：HR=0.53，95%CI=0.42-0.68，P<0.00001；BRCAm：HR=0.30，95%CI=0.26-0.34，P<0.00001；BRCA 状态未分类：HR=0.52，95%CI=0.41-0.66，P<0.00001；BRCA1m：HR=0.38，95%CI=0.29-0.48，P<0.00001；BRCA2m：HR=0.23，95%CI=0.10-0.57，P=0.001）。我们的分析显示 PARPi 组 3 级及以上（3 至 4 级）AE 和严重 AE 的发生率分别为 55.19%和 26.29%。
本荟萃分析表明，PARPi 治疗可显著改善卵巢癌患者的 PFS，但对 OS 无获益。然而，该治疗与 3 级及以上 AE 和严重 AE 的风险显著增加相关。
