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療效：隨機對照試驗的薈萃分析

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

尼拉帕利是一種多腺苷二磷酸核糖聚合酶（PARP）抑制劑，已顯示出作為晚期卵巢癌患者維持療法的臨床益處。

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

我們對隨機對照試驗（RCTs）進行了系統(tǒng)回顧和薈萃分析，以評估尼拉帕利作為晚期卵巢癌患者鉑類化療后維持治療的療效。我們搜索了PubMed、Embase和Cochrane Central Register of Controlled Trials數(shù)據(jù)庫，查找截至2024年1月17日發(fā)表的RCTs。使用隨機效應模型匯總了帶有95%置信區(qū)間（CI）的危險比（HR）和比值比（OR）。我們關注的終點指標是至首次后續(xù)治療時間（TFST）和無進展生存期（PFS）。我們針對BRCA突變、HRD陽性、HRD陰性、對鉑類治療的反應以及新診斷的疾病進行了亞組分析。

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%）.

研究結果

共有四項隨機對照試驗（RCTs納入分析，共涉及1,935名患者，其中1,291名患者接受尼拉帕利治療，644名患者接受安慰劑治療。尼拉帕利在整體人群中顯著改善了無進展生存期（PFS）（HR 0.45；95% CI 0.31-0.66；p<0.0001；I2=82%），在BRCA突變患者（HR 0.32；95% CI 0.25-0.43；p<0.00001；I2=21%）、HRD陽性患者（HR 0.39；95% CI 0.30-0.51；p<0.00001；I2=40%）、HRD陰性患者（HR 0.45；95% CI 0.36-0.57；p<0.00001；I2=0%）以及新診斷癌癥患者（HR 0.59；95% CI 0.39-0.73；p<0.0001；I2=68%）中也觀察到顯著效果。尼拉帕利組的至首次后續(xù)治療時間（TFST）更長（HR 0.48；95% CI 0.33-0.68；p<0.0001；I2=80%）。此外，鉑類治療后達完全緩解和部分緩解的組間對比在統(tǒng)計學上無顯著差異（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.

研究結論

尼拉帕利顯著改善晚期卵巢癌患者的無進展生存期（PFS），并延長了至首次后續(xù)治療的時間。