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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 - PubMed

  • ️Mon Jan 01 2024

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. 2024.

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.

Copyright © 2024 Song, Hou, Ma, Yan and Gao.

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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.

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References

    1. Buckowitz A, Knaebel HP, Benner A, Blaker H, Gebert J, Kienle P, et al. . Microsatellite instability in colorectal cancer is associated with local lymphocyte infiltration and low frequency of distant metastases. Br J Cancer. (2005) 92:1746–53. doi: 10.1038/sj.bjc.6602534 - DOI - PMC - PubMed
    1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. (2018) 68:394–424. doi: 10.3322/caac.21492 - DOI - PubMed
    1. Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut. (2017) 66:683–91. doi: 10.1136/gutjnl-2015-310912 - DOI - PubMed
    1. Dekker E, Tanis PJ, Vleugels JLA, Kasi PM, Wallace MB. Colorectal cancer. Lancet. (2019) 394:1467–80. doi: 10.1016/S0140-6736(19)32319-0 - DOI - PubMed
    1. Baidoun F, Elshiwy K, Elkeraie Y, Merjaneh Z, Khoudari G, Sarmini MT, et al. . Colorectal cancer epidemiology: recent trends and impact on outcomes. Curr Drug Targets. (2020) 22:998–1009. doi: 10.2174/1389450121999201117115717 - DOI - PubMed

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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.