免疫检查点抑制剂在熟练错配修复（pMMR）/非微卫星不稳定高（non-MSI-H）转移性结直肠癌中的疗效和安全性：基于 39 个队列包含 1723 名患者的研究。

Efficacy and safety of immune checkpoint inhibitors in Proficient Mismatch Repair (pMMR)/ Non-Microsatellite Instability-High (non-MSI-H) metastatic colorectal cancer: a study based on 39 cohorts incorporating 1723 patients.

机构信息

Department of Oncology, Molecular Oncology Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China.

Department of Oncology, National Regional Medical Center, Binhai Campus of The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China.

出版信息

BMC Immunol. 2023 Sep 1;24(1):27. doi: 10.1186/s12865-023-00564-1.

DOI:10.1186/s12865-023-00564-1

PMID:37658314

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10472580/

Abstract

PURPOSE

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).

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

目的

本研究旨在评估免疫检查点抑制剂（ICI）在微卫星高度不稳定（MSI-H）/错配修复 proficient（pMMR）型转移性结直肠癌（mCRC）中的疗效和安全性。

方法

检索电子数据库以确定相关试验。主要终点为汇总客观缓解率（ORR）和疾病控制率（DCR）。对基于 ICI 的方案、治疗线和 RAS 状态进行分层分析。

结果

共纳入来自 39 个队列的 1723 例 mCRC 患者。在 pMMR/non-MSI-H mCRC 中，ICI 联合治疗的汇总 ORR、DCR、12 个月总生存率（OS）率和 6 个月无进展生存率（PFS）率分别为 8.5%（95%CI：4.4%-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，在 pMMR/non-MSI-H mCRC 中，ICI 联合治疗与非 ICI 联合治疗在 PFS（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）方面均无显著差异。值得注意的是，ICI 联合抗血管内皮生长因子（VEGF）药物加化疗在 pMMR/non-MSI-H mCRC 中显示出优异的疗效（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%；与非 ICI 联合治疗相比：HR=0.9，95%CI：0.8-1.0，P=0.02），尤其是作为一线治疗（ORR=74.2%，95%CI：61.4%-85.4%；DCR=98.7%，95%CI：92.0%-100.0%），且未观察到额外的治疗相关不良事件（TRAEs）。