Wang Wei, Mei Zubing, Chen Yajie, Jiang Jian, Qu Yanli, Saifuding Keyoumu, Zhou Ning, Bulibu Gilisihan, Tang Yong, Zhai Xinyu, Jiang Zhi
Department of Digestive Internal Medicine, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xin Jiang Province.
Department of Anorectal Surgery, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine.
Int J Surg. 2025 Jan 1;111(1):1357-1372. doi: 10.1097/JS9.0000000000002007.
Mismatch repair deficient (dMMR) and microsatellite instability-high (MSI-H) cancers are associated with an increased number of somatic mutations, which can render tumors more susceptible to immune checkpoint blockade. However, a comprehensive evaluation of the efficacy profile of immune checkpoint inhibitors in this patient population across multiple cancer types is lacking. This study aims to address this knowledge gap by synthesizing data from phase I-III clinical trials.
A systematic search was conducted in PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Google Scholar from inception until June 2024. Eligible studies included randomized controlled trials (RCTs), nonrandomized comparative studies, and single-arm trials investigating immune checkpoint inhibitors in patients with dMMR/MSI-H advanced cancers. The primary outcome was objective response rate (ORR), and the secondary outcomes included disease control rate (DCR), 1-year, 2-year, and 3-year overall survival (OS) and progression-free survival (PFS) rates. Subgroup analyses were conducted for the primary outcome stratified by major study characteristics.
Of the 10 802 identified studies, 19 trials in 25 studies totaling 2052 participants met the inclusion criteria and were included in the meta-analysis. The pooled ORR was 41.7% (95% CI, 35.7-47.7%). The pooled DCR was 68.9% (95% CI, 62.2-75.7%). The pooled 12-month, 24-month, and 36-month OS rates were 29.1% (95% CI, 19.9-38.3%), 35.8% (95% CI, 23.6-48.0%), and 35.8% (95% CI, 23.6-48.0%), respectively. The pooled 12-month, 24-month, and 36-month PFS rates were 46.4% (95% CI, 39.1-53.8%), 67.0% (95% CI, 55.2-78.8%), and 63.1% (95% CI, 37.3-88.9%), respectively.
The study establishes the therapeutic potential of immune checkpoint inhibitors in dMMR/MSI-H advanced cancers, highlighting the importance of MSI status in this context. Further, head-to-head comparisons are needed to conclusively determine MSI's predictive power relative to proficient mismatch repair/microsatellite stable (pMMR/MSS) tumors.
错配修复缺陷（dMMR）和微卫星高度不稳定（MSI-H）癌症与体细胞突变数量增加有关，这会使肿瘤更容易受到免疫检查点阻断的影响。然而，目前缺乏对这一患者群体中多种癌症类型的免疫检查点抑制剂疗效的全面评估。本研究旨在通过综合来自I-III期临床试验的数据来填补这一知识空白。
从创刊至2024年6月，在PubMed、Embase、Cochrane对照试验中央注册库和谷歌学术进行了系统检索。符合条件的研究包括随机对照试验（RCT）、非随机对照研究和单臂试验，这些试验研究了dMMR/MSI-H晚期癌症患者使用免疫检查点抑制剂的情况。主要结局是客观缓解率（ORR），次要结局包括疾病控制率（DCR）、1年、2年和3年总生存率（OS）以及无进展生存率（PFS）。根据主要研究特征对主要结局进行亚组分析。
在10802项检索到的研究中，25项研究中的19项试验共2052名参与者符合纳入标准并被纳入荟萃分析。汇总的ORR为41.7%（95%CI，35.7-47.7%）。汇总的DCR为68.9%（95%CI，62.2-75.7%）。汇总的12个月、24个月和36个月OS率分别为29.1%（95%CI，19.9-38.3%）、35.8%（95%CI，23.6-48.0%）和35.8%（95%CI，23.6-48.0%）。汇总的12个月、24个月和36个月PFS率分别为46.4%（95%CI，39.1-53.8%）、67.0%（95%CI，55.2-78.8%）和63.1%（95%CI，37.3-88.9%）。
该研究确立了免疫检查点抑制剂在dMMR/MSI-H晚期癌症中的治疗潜力，突出了MSI状态在此背景下的重要性。此外，需要进行直接比较以最终确定MSI相对于错配修复功能正常/微卫星稳定（pMMR/MSS）肿瘤的预测能力。
