Effectiveness and Safety of Immune Checkpoint Inhibitors in Colorectal Cancer: A Systematic Review of Real-World Studies

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.