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Meta-Analysis
. 2024 Nov 1:15:1485303.
doi: 10.3389/fimmu.2024.1485303. eCollection 2024.

Efficacy and safety of PD-1/PD-L1 and CTLA-4 immune checkpoint inhibitors in the treatment of advanced colorectal cancer: a systematic review and meta-analysis

Dandan Song #  1   2 , Shufu Hou #  3 , Ning Ma #  4 , Bing Yan  3 , Jing Gao  2
Affiliations
Meta-Analysis

Efficacy and safety of PD-1/PD-L1 and CTLA-4 immune checkpoint inhibitors in the treatment of advanced colorectal cancer: a systematic review and meta-analysis

Dandan Song et al. Front Immunol. .

Abstract

Background: The efficacy and safety of PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors in the treatment of advanced colorectal cancer is controversial. This meta-analysis aimed to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors for advanced colorectal cancer.

Methods: PubMed, Embase, the Cochrane Library, and Web of Science databases were systematically searched for relevant studies. Outcomes including median progression-free survival (mPFS), median overall survival (mOS), overall response rate (ORR), disease control rate (DCR), treatment-related adverse events (TRAEs) and ≥grade 3 TRAEs were extracted for further analysis. The risk of bias was assessed by subgroup analysis.

Results: 12 articles with 566 patients were identified and subjected to meta-analysis. With regard to survival analysis, the pooled mOS and mPFS were 6.66 months (95%CI 4.85-9.16) and 2.92 months (95%CI 2.23-3.83), respectively. In terms of tumor response, the pooled ORR and DCR were 21% (95%CI 6%-41%) and 49% (95%CI 27%-71%), respectively. The pooled AEs rate and ≥ grade 3 AEs rate were 94% (95%CI 86%-99%) and 44% (95%CI 30%-58%).

Conclusion: PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors have shown promising clinical responses in the treatment of colorectal cancer (CRC). Although the incidence of adverse reactions is high, they are generally tolerable.

Systematic review registration: https://inplasy.com/, identifier INPLASY202480030.

Keywords: CTLA-4; PD-1; PD-L1; colorectal cancer; immune checkpoint inhibitors; immunotherapy.

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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
Prisma flowchart illustrating the literature selection process.
Figure 2
Figure 2
Forest plot for the (A) median overall survival (mOS) and (B) median progression-free survival (mPFS) in aCRC patients receiving PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors.
Figure 3
Figure 3
Forest plot for the (A) Objective response rate (ORR) and (B) Disease control rate (DCR) in aCRC patients receiving PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors.
Figure 4
Figure 4
Forest plot for the (A) adverse events(AEs) rate and (B) and ≥grade 3 AEs rate in aCRC patients receiving PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors.
See this image and copyright information in PMC

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MeSH terms

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was funded by Servier. The funders had no role or input in the study itself.