Kong Leping, Yiu Chin Hang, Lu Christine Y
The University of Sydney School of Pharmacy, Camperdown, NSW, Australia.
Kolling Institute, Faculty of Medicine and Health, The University of Sydney and the Northern Sydney Local Health District, Sydney, NSW, Australia.
Curr Oncol Rep. 2025 May 13. doi: 10.1007/s11912-025-01676-0.
Immune checkpoint inhibitors (ICIs) have demonstrated significant efficacy in the treatment of colorectal cancer (CRC). However, most evidence has come from clinical trials with strict eligibility criteria. Understanding real-world effectiveness and safety of ICIs in CRC is important to guide routine clinical practice across diverse populations.
A systematic review following PRISMA guidelines was conducted to identify observational studies evaluating ICI-based regimens compared to conventional or combination therapies in patients with CRC. Three databases (MEDLINE, Embase, and Scopus) were searched from inception through March 15, 2025. Eligible studies reported at least one efficacy outcome (e.g., progression-free survival [PFS], overall survival [OS], etc.) and/or safety outcome (e.g., adverse events) among real-world populations with CRC treated with ICIs. Study quality was assessed using the Newcastle-Ottawa Scale, and a narrative synthesis was performed to summarize the key findings. Eleven real-world studies met the inclusion criteria, encompassing data from 2,049 patients. In MSI-H/dMMR metastatic CRC, real-world findings aligned with the survival benefits observed in clinical trials, demonstrating improved PFS and OS compared to conventional therapies. For MSS/pMMR metastatic CRC, combining ICIs with other agents (e.g., tyrosine kinase inhibitors or chemotherapy) showed improvements but yielded conflicting results. Overall, the safety profiles were comparable to conventional therapies, with treatment-related adverse events occurring at similar rates. Real-world evidence supports the efficacy of ICI monotherapy in MSI-H/dMMR metastatic CRC and suggests potential benefits of ICI-based combination therapies in MSS/pMMR metastatic CRC. However, most of the data are derived from small, single-center cohorts, which limit their generalizability. Further multi-center studies are needed, especially to assess the efficacy of ICI-based combination therapies in the broader CRC population.
免疫检查点抑制剂（ICI）在结直肠癌（CRC）治疗中已显示出显著疗效。然而，大多数证据来自具有严格入选标准的临床试验。了解ICI在CRC中的真实世界有效性和安全性对于指导不同人群的常规临床实践非常重要。
按照PRISMA指南进行了一项系统评价，以确定评估ICI方案与传统或联合疗法相比在CRC患者中的观察性研究。检索了三个数据库（MEDLINE、Embase和Scopus），检索时间从数据库创建至2025年3月15日。符合条件的研究报告了在接受ICI治疗的CRC真实世界人群中至少一项疗效结果（如无进展生存期[PFS]、总生存期[OS]等）和/或安全性结果（如不良事件）。使用纽卡斯尔-渥太华量表评估研究质量，并进行叙述性综合以总结关键发现。11项真实世界研究符合纳入标准，涵盖2049例患者的数据。在微卫星高度不稳定/错配修复缺陷（MSI-H/dMMR）转移性CRC中，真实世界的研究结果与临床试验中观察到的生存获益一致，与传统疗法相比，PFS和OS均有改善。对于微卫星稳定/错配修复功能正常（MSS/pMMR）转移性CRC，将ICI与其他药物（如酪氨酸激酶抑制剂或化疗）联合使用显示出改善，但结果相互矛盾。总体而言，安全性与传统疗法相当，治疗相关不良事件的发生率相似。真实世界证据支持ICI单药治疗在MSI-H/dMMR转移性CRC中的疗效，并表明基于ICI的联合疗法在MSS/pMMR转移性CRC中具有潜在益处。然而，大多数数据来自小型单中心队列，这限制了其普遍性。需要进一步开展多中心研究，尤其是评估基于ICI的联合疗法在更广泛的CRC人群中的疗效。
