Cui Jie, Zhao Yue-Chen, She Li-Zhen, Wang Tie-Jun
Department of Radiation Oncology, The Second Hospital of Jilin University, Changchun, Jilin, China.
Front Oncol. 2024 May 3;14:1391546. doi: 10.3389/fonc.2024.1391546. eCollection 2024.
The objective of this network meta-analysis is to systematically compare the efficacy of diverse progestin-based combination regimens in treating patients diagnosed with endometrial cancer or atypical endometrial hyperplasia. The primary goal is to discern the optimal combination treatment regimen through a comprehensive examination of their respective effectiveness.
We systematically searched four prominent databases: PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials, for randomized controlled trials addressing the efficacy of progestins or progestin combinations in the treatment of patients with endometrial cancer or atypical endometrial hyperplasia. The search spanned from the inception of these databases to December 2023. Key outcome indicators encompassed survival indices, criteria for assessing efficacy, as well as pregnancy and relapse rate. This study was registered in PROSPERO (CRD42024496311).
From the 1,558 articles initially retrieved, we included 27 studies involving a total of 5,323 subjects in our analysis. The results of the network meta-analysis revealed that the mTOR inhibitor+megestrol acetate (MA)+tamoxifen regimen secured the top rank in maintaining stable disease (SD) (SUCRA=73.4%) and extending progression-free survival (PFS) (SUCRA=72.4%). Additionally, the progestin combined with tamoxifen regimen claimed the leading position in enhancing the partial response (PR) (SUCRA=75.2%) and prolonging overall survival (OS) (SUCRA=80%). The LNG-IUS-based dual progestin regimen emerged as the frontrunner in improving the complete response (CR) (SUCRA=98.7%), objective response rate (ORR) (SUCRA=99.1%), pregnancy rate (SUCRA=83.7%), and mitigating progression (SUCRA=8.0%) and relapse rate (SUCRA=47.4%). In terms of safety, The LNG-IUS-based dual progestin regimen had the lowest likelihood of adverse events (SUCRA=4.2%), while the mTOR inhibitor regimen (SUCRA=89.2%) and mTOR inbitor+MA+tamoxifen regimen (SUCRA=88.4%) had the highest likelihood of adverse events.
Patients diagnosed with endometrial cancer or atypical endometrial hyperplasia exhibited the most favorable prognosis when undergoing progestin combination therapy that included tamoxifen, mTOR inhibitor, or LNG-IUS. Notably, among these options, the LNG-IUS-based dual progestin regimen emerged as particularly promising for potential application.
https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024496311.
本网络荟萃分析的目的是系统比较多种基于孕激素的联合治疗方案在治疗子宫内膜癌或非典型子宫内膜增生患者中的疗效。主要目标是通过全面考察各自的有效性来辨别最佳联合治疗方案。
我们系统检索了四个著名数据库：PubMed、Web of Science、Embase和Cochrane对照试验中央注册库，以查找关于孕激素或孕激素联合治疗子宫内膜癌或非典型子宫内膜增生患者疗效的随机对照试验。检索时间跨度从这些数据库建立至2023年12月。关键结局指标包括生存指数、疗效评估标准以及妊娠率和复发率。本研究已在PROSPERO（CRD42024496311）注册。
在最初检索到的1558篇文章中，我们纳入了27项研究，共计5323名受试者进行分析。网络荟萃分析结果显示，mTOR抑制剂+醋酸甲地孕酮（MA）+他莫昔芬方案在维持疾病稳定（SD）（累积排序曲线下面积[SUCRA]=73.4%）和延长无进展生存期（PFS）（SUCRA=72.4%）方面排名第一。此外，孕激素联合他莫昔芬方案在提高部分缓解（PR）（SUCRA=75.2%）和延长总生存期（OS）（SUCRA=80%）方面占据领先地位。基于左炔诺孕酮宫内节育系统（LNG-IUS）的双孕激素方案在改善完全缓解（CR）（SUCRA=98.7%）、客观缓解率（ORR）（SUCRA=99.1%）、妊娠率（SUCRA=83.7%）以及减轻疾病进展（SUCRA=8.0%）和复发率（SUCRA=47.4%）方面成为佼佼者。在安全性方面，基于LNG-IUS的双孕激素方案发生不良事件的可能性最低（SUCRA=4.2%），而mTOR抑制剂方案（SUCRA=89.2%）和mTOR抑制剂+MA+他莫昔芬方案（SUCRA=88.4%）发生不良事件的可能性最高。
被诊断为子宫内膜癌或非典型子宫内膜增生的患者在接受包含他莫昔芬、mTOR抑制剂或LNG-IUS的孕激素联合治疗时预后最佳。值得注意的是，在这些选择中，基于LNG-IUS的双孕激素方案在潜在应用方面显得特别有前景。
