This study was designed to investigate the efficacy and safety of immune checkpoint inhibitors (ICIs)-based therapy in proficient mismatch repair (pMMR)/non-microsatellite instability-high (non-MSI-H) metastatic colorectal cancer (mCRC). Electronic databases were screened to identify relevant trials. The primary endpoints were pooled objective response rate (ORR) and disease control rate (DCR). Stratified analysis was accomplished on ICIs-based regimens, treatment lines and RAS status. Totally, 1723 mCRC patients from 39 cohorts were included. The pooled ORR, DCR, 12-month overall survival (OS) rate and 6-month progression-free survival (PFS) rate of ICIs-based therapy in pMMR/non-MSI-H mCRC were 8.5% (95% CI: 4.4%-13.5%), 48.2% (95% CI: 37.8%-58.6%), 52.3% (95% CI: 46.4%-58.1%) and 32.8% (95% CI: 23.5%-42.7%) respectively. As a whole, no significantly differences were shown between ICIs-based and non-ICIs-based therapy for pMMR/non-MSI-H mCRC in terms of both PFS (HR = 1.0, 95% CI: 0.9–1.1, P = 0.91) and OS (HR = 1.0, 95% CI: 0.9–1.2, P = 0.51). It was worth noting that the addition of ICIs to anti-vascular endothelial growth factor (VEGF) agent plus chemotherapy displayed excellent efficacy in pMMR/non-MSI-H mCRC (ORR = 42.4%, 95% CI: 10.0%-78.6%; DCR = 92.0%, 95% CI: 68.3%-100.0%; 12-month OS rate = 71.4%, 95% CI: 50.0%-89.1%; 6-month PFS rate = 55.2%, 95% CI: 24.8%-83.8%; and PFS (compared with non-ICIs-based therapy): HR = 0.9, 95% CI: 0.8–1.0, P = 0.02), especially served as first-line therapy (ORR = 74.2%, 95% CI: 61.4%-85.4%; DCR = 98.7%, 95% CI: 92.0%-100.0%); and without additional treatment related adverse events (TRAEs) were observed. ICIs-based combination therapy, especially the addition of ICIs to first-line anti-VEGF agent plus chemotherapy, is promising in pMMR/non-MSI-H mCRC with good efficacy and controllable toxicity.

中文翻译：

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免疫检查点抑制剂在熟练错配修复 (pMMR)/非微卫星不稳定性高 (非 MSI-H) 转移性结直肠癌中的功效和安全性：一项基于纳入 1723 名患者的 39 个队列的研究

本研究旨在探讨基于免疫检查点抑制剂 (ICIs) 的治疗在熟练错配修复 (pMMR)/非微卫星不稳定性高 (非 MSI-H) 转移性结直肠癌 (mCRC) 中的疗效和安全性。筛选电子数据库以确定相关试验。主要终点是汇总客观缓解率（ORR）和疾病控制率（DCR）。对基于 ICI 的治疗方案、治疗线和 RAS 状态进行了分层分析。总共纳入了来自 39 个队列的 1723 名 mCRC 患者。pMMR/非 MSI-H mCRC 中基于 ICI 的治疗的汇总 ORR、DCR、12 个月总生存 (OS) 率和 6 个月无进展生存 (PFS) 率为 8.5%（95% CI：4.4）分别为 %-13.5%)、48.2% (95% CI: 37.8%-58.6%)、52.3% (95% CI: 46.4%-58.1%) 和 32.8% (95% CI: 23.5%-42.7%)。总体而言，基于 ICI 和非 ICI 的 pMMR/非 MSI-H mCRC 治疗在 PFS 方面没有显着差异（HR = 1.0，95% CI：0.9–1.1，P = 0.91） ）和 OS（HR = 1.0，95% CI：0.9–1.2，P = 0.51）。值得注意的是，抗血管内皮生长因子（VEGF）药物联合化疗联合ICIs对pMMR/non-MSI-H mCRC显示出优异的疗效（ORR = 42.4%，95% CI：10.0%-78.6%； DCR = 92.0%，95% CI：68.3%-100.0%；12 个月 OS 率 = 71.4%，95% CI：50.0%-89.1%；6 个月 PFS 率 = 55.2%，95% CI：24.8%- 83.8%；PFS（与非 ICI 治疗相比）：HR = 0.9，95% CI：0.8–1.0，P = 0.02），特别是作为一线治疗（ORR = 74.2%，95% CI： 61.4%-85.4%；DCR = 98.7%，95% CI：92.0%-100.0%）；并且在没有额外治疗的情况下观察到相关不良事件（TRAE）。基于ICIs的联合治疗，特别是在一线抗VEGF药物联合化疗的基础上添加ICIs，在pMMR/non-MSI-H mCRC中具有良好的疗效和可控的毒性，具有广阔的前景。