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

BackgroundColorectal 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...

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Main Authors: Qi-Jing Zhang, Jia-xin Zhou, Da-hai Hu, Jing-hua Pan, Si-min Luo, Qi Yao
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1514485/full
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author Qi-Jing Zhang
Qi-Jing Zhang
Jia-xin Zhou
Jia-xin Zhou
Da-hai Hu
Jing-hua Pan
Jing-hua Pan
Si-min Luo
Si-min Luo
Qi Yao
author_facet Qi-Jing Zhang
Qi-Jing Zhang
Jia-xin Zhou
Jia-xin Zhou
Da-hai Hu
Jing-hua Pan
Jing-hua Pan
Si-min Luo
Si-min Luo
Qi Yao
author_sort Qi-Jing Zhang
collection DOAJ
description BackgroundColorectal 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.MethodsA 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.ResultsFour 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.ConclusionExisting 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 registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024520150.
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spelling doaj-art-2a0b0f7b646c40a0908ccf1d73217d312025-08-20T02:33:06ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-06-011510.3389/fonc.2025.15144851514485The 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 trialsQi-Jing Zhang0Qi-Jing Zhang1Jia-xin Zhou2Jia-xin Zhou3Da-hai Hu4Jing-hua Pan5Jing-hua Pan6Si-min Luo7Si-min Luo8Qi Yao9Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, ChinaSchool of Medicine, Jinan University, Guangzhou, Guangdong, ChinaDepartment of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, ChinaInternational School, Jinan University, Guangzhou, Guangdong, ChinaDepartment of Sports Medicine, The First Affiliated Hospital, Guangdong Provincial Key Laboratory of Speed Capability, The Guangzhou Key Laboratory of Precision Orthopedics and Regenerative Medicine, Jinan University, Guangzhou, ChinaDepartment of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, ChinaChaoshan Hospital, The First Affiliated Hospital of Jinan University, Chaozhou, ChinaChaoshan Hospital, The First Affiliated Hospital of Jinan University, Chaozhou, ChinaDepartment of Bone and Joint Surgery, The First Affiliated Hospital, Jinan University, Guangzhou, ChinaDepartment of Anorectal Surgery, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital), Shenzhen, ChinaBackgroundColorectal 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.MethodsA 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.ResultsFour 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.ConclusionExisting 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 registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024520150.https://www.frontiersin.org/articles/10.3389/fonc.2025.1514485/fullcolorectal cancerimmune checkpoint inhibitorsefficacysafetymeta-analysis
spellingShingle Qi-Jing Zhang
Qi-Jing Zhang
Jia-xin Zhou
Jia-xin Zhou
Da-hai Hu
Jing-hua Pan
Jing-hua Pan
Si-min Luo
Si-min Luo
Qi Yao
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
Frontiers in Oncology
colorectal cancer
immune checkpoint inhibitors
efficacy
safety
meta-analysis
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic colorectal cancer
immune checkpoint inhibitors
efficacy
safety
meta-analysis
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1514485/full
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