Landre Thierry, Des Guetz Gaëtan
Assistance Publique Hôpitaux de Paris (AP-HP), Hôpital René Muret, Hôpitaux Universitaires de Paris Seine-St-Denis, Avenue du Dr Schaeffner, 93270, Sevran, France.
Service d'Oncologie Médicale, Faculté de Médecine, Centre Hospitalier de St-Denis, Université Sorbonne Paris Nord, St-Denis, France.
Cancer Immunol Immunother. 2025 Feb 25;74(4):122. doi: 10.1007/s00262-025-03980-x.
Microsatellite instability-high (MSI-H) cancers are linked to exceptional benefit from immune checkpoint inhibitors (ICIs), but studies on their efficacy across various MSI-H cancer types are limited.
Randomized clinical trials (RCTs) comparing ICIs to chemotherapy in advanced MSI-H/dMMR cancers were systematically reviewed. Eligible studies included 13 RCTs with 1633 MSI-H patients across colorectal, gastric, and endometrial cancers. Data were analyzed using hazard ratios for progression-free survival (PFS) and overall survival (OS), with subgroup analyses by tumor type. Statistical heterogeneity was assessed using Cochrane's Q and I.
Immunotherapy significantly improved PFS and OS in MSI-H patients, with an HR for OS of 0.35 (95% CI 0.27-0.46; p < 0.00001) versus 0.81 for MSS patients. PFS showed a 64% reduced risk of progression (HR = 0.36, 95% CI 0.28-0.46; p < 0.0001). Subgroup analyses highlighted PFS benefits across tumor types: colorectal (HR = 0.28, 95% CI 0.11-0.73), gastric (HR = 0.43, 95% CI 0.27-0.68), and endometrial cancers (HR = 0.34, 95% CI 0.27-0.42).
This meta-analysis establishes MSI-H as a predictive biomarker for ICIs, supporting its role in therapy selection and underscoring the need for MSI-H/dMMR-focused clinical trials.
微卫星高度不稳定（MSI-H）癌症与免疫检查点抑制剂（ICI）的显著获益相关，但关于其在各种MSI-H癌症类型中的疗效研究有限。
系统回顾了比较ICI与化疗在晚期MSI-H/dMMR癌症中的随机临床试验（RCT）。符合条件的研究包括13项RCT，涉及1633例患有结直肠癌、胃癌和子宫内膜癌的MSI-H患者。使用无进展生存期（PFS）和总生存期（OS）的风险比进行数据分析，并按肿瘤类型进行亚组分析。使用Cochrane的Q和I评估统计异质性。
免疫疗法显著改善了MSI-H患者的PFS和OS，MSI-H患者的OS风险比为0.35（95%置信区间0.27-0.46；p<0.00001），而错配修复功能健全（MSS）患者为0.81。PFS显示疾病进展风险降低64%（风险比=0.36，95%置信区间0.28-0.46；p<0.0001）。亚组分析突出了各肿瘤类型的PFS获益：结直肠癌（风险比=0.28，95%置信区间0.11-0.73）、胃癌（风险比=0.43，95%置信区间0.27-0.68）和子宫内膜癌（风险比=0.34，9置信区间0.27-0.42）。
这项荟萃分析确立了MSI-H作为ICI的预测生物标志物，支持其在治疗选择中的作用，并强调了开展以MSI-H/dMMR为重点的临床试验的必要性。
