Immune checkpoint inhibitors for patients with mismatch repair deficient or microsatellite instability-high advanced cancers: a meta-analysis of phase I–III clinical trials

作者：Wei Wang, Zubing Mei, Y. Chen, Jian Jiang, Yanli Qu, Saifuding Keyoumu, Ning Zhou, Gilisihan Bulibu, Yong Tang, Xinyu Zhai, Zhi Jiang · 发表于：International Journal of Surgery · 年份：2024 · DOI：10.1097/js9.0000000000002007 · 被引用次数：7 · 研究领域：Genetic factors in colorectal cancer、Cancer Immunotherapy and Biomarkers、Multiple and Secondary Primary Cancers

BACKGROUND: 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. METHODS: 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. RESULTS: 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%...