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Review
. 2025 Jun 24;17(13):2125.
doi: 10.3390/cancers17132125.

Immune Checkpoint Inhibitors for Metastatic Colorectal Cancer: A Systematic Review

Alice Gilson  1 , Vincent Tan  2 , Thibaud Koessler  3 , Jeremy Meyer  1 , Guillaume Meurette  1 , Émilie Liot  1 , Frédéric Ris  1 , Vaihere Delaune  1   4
Affiliations
Review

Immune Checkpoint Inhibitors for Metastatic Colorectal Cancer: A Systematic Review

Alice Gilson et al. Cancers (Basel). .

Abstract

Background: Colorectal cancer is a significant health concern. Immunotherapy has become a promising approach in colorectal cancer, offering a wider array of therapeutic strategies. This study aims to summarize the current evidence regarding the use of checkpoint inhibitors in metastatic colorectal cancer.

Methods: A systematic review of relevant clinical trials and randomized controlled trials (RCTs) assessing checkpoint inhibitors, published between January 2019 and January 2025, was conducted on Medline, Web of Science, and Cochrane. Progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were the primary outcomes. Studies focusing on other types of immunotherapy, non-clinical trials, pre-clinical trials, and study protocols were excluded.

Results: 48 studies were included. Checkpoint inhibitors demonstrated significant efficacy in microsatellite instability (MSI) metastatic colorectal cancer (mCRC). In microsatellite stability (MSS) mCRC, immunotherapy was less effective, and combination strategies with chemotherapy or targeted therapies yielded mixed results. Grade ≥ 3 treatment-related adverse events (TRAEs) were common in combination regimens.

Conclusion: Immunotherapy has revolutionized MSI mCRC treatment while treating MSS CRC with these molecules remains unconvincing. Combination strategies and novel agents may offer potential but require further research to prove efficacy.

Keywords: checkpoint inhibitor; colorectal cancer; cytotoxic T lymphocyte antigen 4 protein (CTLA-4); immunotherapy; microsatellite instability (MSI); microsatellite stability (MSS); programmed cell death protein 1 (PD-1); programmed death-ligand 1 (PD-L1).

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
PRISMA flow diagram for studies included in this qualitative review.
See this image and copyright information in PMC

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