PDF(Pubmed)
Abstract：
Background: Poly (ADP-ribose) polymerase (PARP) inhibitor and antiangiogenic agent monotherapy have shown to be effective as maintenance treatment in patients with ovarian cancer (OC). However, there is currently a lack of evidence-based study to directly compare the effects of combination therapy with these two drugs. Therefore, this study aimed to compare the efficacy and safety of combination therapy with PARP inhibitors and antiangiogenic agents in women with OC using a meta-analysis. Methods: An exhaustive search of literature was undertaken using multiple databases, including PubMed, Web of Science, Embase, and the Cochrane Library to identify pertinent randomized controlled trials (RCTs) published up until 17 December 2023. The data on progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were pooled. We computed the pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) for PFS and OS, along with the relative risks (RRs) and 95% CIs for AEs. Trial sequential analysis, heterogeneity test, sensitivity analysis, and publication bias assessment were performed. Stata 12.0 and Software R 4.3.1 were utilized for all analyses. Results: This meta-analysis included 7 RCTs with a total of 3,388 participants. The overall analysis revealed that combination therapy of PARP inhibitors and antiangiogenic agents significantly improved PFS (HR = 0.615, 95% CI = 0.517-0.731; 95% PI = 0.379-0.999), but also increased the risk of AEs, including urinary tract infection (RR = 1.500, 95% CI = 1.114-2.021; 95% PI = 0.218-10.346), fatigue (RR = 1.264, 95% CI = 1.141-1.400; 95% PI = 1.012-1.552), headache (RR = 1.868, 95% CI = 1.036-3.369; 95% PI = 0.154-22.642), anorexia (RR = 1.718, 95% CI = 1.320-2.235; 95% PI = 0.050-65.480), and hypertension (RR = 5.009, 95% CI = 1.103-22.744; 95% PI = 0.016-1580.021) compared with PARP inhibitor or antiangiogenic agent monotherapy. Our study has not yet confirmed the benefit of combination therapy on OS in OC patients (HR = 0.885, 95% CI = 0.737-1.063). Additionally, subgroup analyses further showed that combination therapy resulted in an increased risk of AEs, encompassing thrombocytopenia, vomiting, abdominal pain, proteinuria, fatigue, headache, anorexia, and hypertension (all p < 0.05). Conclusion: Our study demonstrated the PFS benefit of combination therapy with PARP inhibitors and antiangiogenic agents in patients with OC. The OS result need to be updated after the original trial data is mature. Clinicians should be vigilant of AEs when administering the combination therapy in clinical practice. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023494482.
摘要：
背景：聚（ADP-核糖）聚合酶（PARP）抑制剂和抗血管生成剂单一疗法已显示可有效用于卵巢癌（OC）患者的维持治疗。然而,目前缺乏直接比较这两种药物联合治疗效果的循证研究.因此,本研究旨在通过荟萃分析比较PARP抑制剂和抗血管生成药物联合治疗在女性OC患者中的疗效和安全性.方法：使用多个数据库进行详尽的文献检索，包括PubMed,WebofScience,Embase,和Cochrane图书馆，以确定截至2023年12月17日发表的相关随机对照试验（RCT）。无进展生存期（PFS）的数据，总生存期（OS），和不良事件（AE）进行汇总。我们计算了PFS和OS的合并风险比(HR)及其95%置信区间(CI)，以及不良事件的相对风险(RR)和95%CI。试验序贯分析，异质性检验，敏感性分析，并进行发表偏倚评估.Stata12.0和软件R4.3.1用于所有分析。结果：这项荟萃分析包括7项RCT，共有3,388名参与者。总体分析显示，PARP抑制剂和抗血管生成药物的联合治疗显着改善了PFS（HR=0.615，95％CI=0.517-0.731；95％PI=0.379-0.999），但也增加了AE的风险，包括尿路感染（RR=1.500，95%CI=1.114-2.021；95%PI=0.218-10.346），疲劳(RR=1.264，95%CI=1.141-1.400；95%PI=1.012-1.552)，头痛（RR=1.868，95%CI=1.036-3.369；95%PI=0.154-22.642），厌食症（RR=1.718，95%CI=1.320-2.235；95%PI=0.050-65.480），与PARP抑制剂或抗血管生成剂单一疗法相比，高血压（RR=5.009，95％CI=1.103-22.744；95％PI=0.016-1580.021）。我们的研究尚未证实联合治疗对OC患者OS的益处（HR=0.885，95％CI=0.737-1.063）。此外,亚组分析进一步显示，联合治疗导致AE的风险增加，包括血小板减少症，呕吐,腹痛,蛋白尿,疲劳,头痛,厌食症,和高血压（均p<0.05）。结论：我们的研究证明了PARP抑制剂和抗血管生成药物联合治疗对OC患者的PFS益处。OS结果需要在原始试验数据成熟后进行更新。临床医生在临床实践中给予联合治疗时应警惕AE。系统审查注册：https://www。crd.约克。AC.英国/PROSPERO/,标识符CRD42023494482。
