SYSTEMATIC REVIEW article
Front. Oncol.
Sec. Gastrointestinal Cancers: Colorectal Cancer
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1514485
This article is part of the Research TopicPrimary and Secondary Chemotherapy Resistance in Gastrointestinal Tumors: Key Mechanisms and Ways to Overcome ResistanceView all 9 articles
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
Provisionally accepted
- 1School of Medicine, Jinan University, Guangzhou, Guangdong Province, China
- 2First Affiliated Hospital of Jinan University, Guangzhou, China
- 3International School, Jinan University, Guangzhou, China
- 4Shenzhen People's Hospital, Jinan University, Shenzhen, Guangdong Province, China
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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 metaanalysis 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.
Keywords: colorectal cancer, immune checkpoint inhibitors, efficacy, Safety, Meta-analysis
Received: 17 Dec 2024; Accepted: 27 May 2025.
Copyright: © 2025 Zhang, Zhou, Hu, Pan, Luo and Qi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jinghua Pan, First Affiliated Hospital of Jinan University, Guangzhou, China
Simin Luo, First Affiliated Hospital of Jinan University, Guangzhou, China
Yao Qi, Shenzhen People's Hospital, Jinan University, Shenzhen, 518000, Guangdong Province, China
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