Efficacy of niraparib in patients with advanced ovarian cancer: A meta analysis of randomized controlled trials

尼拉帕利在晚期卵巢癌患者中的疗效：随机对照试验的荟萃分析


First Author: Alice Marinho


Background

Niraparib is a poly-adenosine diphosphate-ribose polymerase （PARP） inhibitor that has shown clinical benefits as a maintenance therapy for patients with advanced ovarian cancer.


研究背景

尼拉帕利是一种多腺苷二磷酸核糖聚合酶（PARP）抑制剂，已显示出作为晚期卵巢癌患者维持疗法的临床益处。


Methods

We conducted a systematic review and meta-analysis of randomized controlled trials（RCTs） evaluating the efficacy of niraparib as maintenance therapy after platinum-based chemotherapy for patients with advanced ovarian cancer. PubMed, Embase, and Cochrane Central Register of Controlled Trials databases were searched for RCTs published up to January 17, 2024. Hazard ratios （HR） and Odds ratio （OR） with 95% confidence intervals （CI） were pooled using a random-effects model. The endpoints of interest were time to first subsequent therapy （TFST） and progression-free survival （PFS）. We performed subgroup analyses for BRCA-mutation, HRD-positive, HRD-negative,response to platinum therapy, and newly diagnosed disease.


研究方法

我们对随机对照试验（RCTs）进行了系统回顾和荟萃分析，以评估尼拉帕利作为晚期卵巢癌患者铂类化疗后维持治疗的疗效。我们搜索了PubMed、Embase和Cochrane Central Register of Controlled Trials数据库，查找截至2024年1月17日发表的RCTs。使用随机效应模型汇总了带有95%置信区间（CI）的危险比（HR）和比值比（OR）。我们关注的终点指标是至首次后续治疗时间（TFST）和无进展生存期（PFS）。我们针对BRCA突变、HRD阳性、HRD阴性、对铂类治疗的反应以及新诊断的疾病进行了亚组分析。


Results

Four RCTs were included, comprising a total of 1,935 patients of whom 1,291 received niraparib and 644 received placebo. Niraparib significantly improved PFS in the overall population （HR 0.45; 95% CI 0.31-0.66; p,0.0001;I²= 82%）, in patients with BRCA mutation （HR 0.32; 95% CI 0.25-0.43; p , 0.00001; I2= 21%）, HRD positivity （HR 0.39; 95% CI 0.30-0.51; p , 0.00001; I²= 40%）, HRD negativity （HR 0.45; 95% CI 0.36-0,57; p , 0.00001; I²= 0%）, and newly diagnosed cancer （HR 0.59; 95% CI 0.39-0.73; p , 0.0001; I²=68%）. The TFST was longer in the niraparib group （HR 0.48; 95% CI 0.33-0.68; p , 0.0001; I²= 80%）.There was no statistical difference between complete and partial response to platinum therapy （OR 1.00; 95% CI 0.87-0.1.16; p = 0.98; I²= 0%）.


研究结果

共有四项随机对照试验（RCTs纳入分析，共涉及1,935名患者，其中1,291名患者接受尼拉帕利治疗，644名患者接受安慰剂治疗。尼拉帕利在整体人群中显著改善了无进展生存期（PFS）（HR 0.45；95% CI 0.31-0.66；p<0.0001；I²=82%），在BRCA突变患者（HR 0.32；95% CI 0.25-0.43；p<0.00001；I²=21%）、HRD阳性患者（HR 0.39；95% CI 0.30-0.51；p<0.00001；I²=40%）、HRD阴性患者（HR 0.45；95% CI 0.36-0.57；p<0.00001；I²=0%）以及新诊断癌症患者（HR 0.59；95% CI 0.39-0.73；p<0.0001；I²=68%）中也观察到显著效果。尼拉帕利组的至首次后续治疗时间（TFST）更长（HR 0.48；95% CI 0.33-0.68；p<0.0001；I²=80%）。此外，铂类治疗后达完全缓解和部分缓解的组间对比在统计学上无显著差异（OR 1.00；95% CI 0.87-1.16；p=0.98；I²=0%）。


Conclusions

Niraparib improves PFS and lowers the time to first subsequent therapy in patients with advanced ovarian cancer. Outcomes and results by studies.


研究结论

尼拉帕利显著改善晚期卵巢癌患者的无进展生存期（PFS），并延长了至首次后续治疗的时间。