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. 2025 Jun 12:15:1514485.
doi: 10.3389/fonc.2025.1514485. eCollection 2025.

The efficacy and safety of chemoimmunotherapy in patients with MSI-L/MSS/pMMR status metastatic colorectal cancer: a systematic review and meta-analysis of randomized controlled trials

Qi-Jing Zhang  1   2 , Jia-Xin Zhou  1   3 , Da-Hai Hu  4 , Jing-Hua Pan  1   5 , Si-Min Luo  5   6 , Qi Yao  7
Affiliations

The efficacy and safety of chemoimmunotherapy in patients with MSI-L/MSS/pMMR status metastatic colorectal cancer: a systematic review and meta-analysis of randomized controlled trials

Qi-Jing Zhang et al. Front Oncol. .

Abstract

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, necessitating innovative therapeutic approaches. Most patients with CRC exhibit microsatellite instability-low/stable (MSI-L/MSS) or proficient mismatch repair (pMMR) status, with chemotherapy being the standard first-line treatment. Chemoimmunotherapy, incorporating immune checkpoint inhibitors (ICIs), has emerged as a potential treatment for MSI-L/MSS/pMMR CRC. This study aimed to comprehensively evaluate the efficacy and safety of chemoimmunotherapy in metastatic CRC (mCRC) patients with MSI-L/MSS/pMMR status.

Methods: A systematic search of PubMed, EMBASE, ScienceDirect, and Cochrane Library was conducted in accordance with PRISMA guidelines, targeting studies published between May 2022 and September 2024. The meta-analyses utilized the generic inverse-variance method with a random effects model.

Results: Four studies encompassing 934 patients with mCRC met the inclusion criteria. The meta-analysis revealed a significant reduction in the risk of progression or death with chemoimmunotherapy compared with chemotherapy (HR: 0.82, 95% CI: 0.70-0.97, P = 0.02). Subgroup analyses based on sex (male vs. female) and ECOG status consistently demonstrated a significant benefit of chemoimmunotherapy in MSI-L/MSS/pMMR tumors. Adverse event analysis indicated an increase in adverse events in the chemoimmunotherapy group.

Conclusion: Existing evidence indicates a statistically significant and clinically meaningful benefit in PFS with chemoimmunotherapy, albeit with a slight increase in all-grade and high-grade toxicities compared to chemotherapy. Future research focusing on biomarkers and innovative treatments is essential for enhancing patient outcomes.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024520150.

Keywords: colorectal cancer; efficacy; immune checkpoint inhibitors; meta-analysis; safety.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Risk of bias summary of RCTs. +low risk,? unclear risk,−high risk.
Figure 2
Figure 2
Risk of bias assessment of RCTs using the weighted summary.
Figure 3
Figure 3
PRISMA flow chart showing the selection of articles for systematic review and meta-analysis.
Figure 4
Figure 4
Forest plots for PFS between research and control groups in mCRC patients.
Figure 5
Figure 5
Forest plots for OS between research and control groups in mCRC patients.
Figure 6
Figure 6
Subgroup analyses according to sex (A) and ECOG status (B).
Figure 7
Figure 7
All-grade (A) and high-grade (B) adverse events rates for research and control arm.
See this image and copyright information in PMC

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References

    1. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: Cancer J Clin. (2024) 74(3):229–63. doi: 10.3322/caac.21834 - DOI - PubMed
    1. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA: Cancer J Clin. (2023) 73:17–48. doi: 10.3322/caac.21763 - DOI - PubMed
    1. Siegel RL, Torre LA, Soerjomataram I, Hayes RB, Bray F, Weber TK, et al. Global patterns and trends in colorectal cancer incidence in young adults. Gut. (2019) 68:2179–85. doi: 10.1136/gutjnl-2019-319511 - DOI - PubMed
    1. Howren A, Sayre EC, Loree JM, Gill S, Brown CJ, Raval MJ, et al. Trends in the incidence of young-onset colorectal cancer with a focus on years approaching screening age: A population-based longitudinal study. J Natl Cancer Inst. (2021) 113:863–8. doi: 10.1093/jnci/djaa220 - DOI - PMC - PubMed
    1. Chambers AC, Dixon SW, White P, Williams AC, Thomas MG, Messenger DE. Demographic trends in the incidence of young-onset colorectal cancer: a population-based study. Br J Surge. (2020) 107:595–605. doi: 10.1002/bjs.11486 - DOI - PMC - PubMed

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