Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2024 Dec 18;24(1):461.
doi: 10.1186/s12876-024-03554-8.

Efficacy and safety of PD-1 and PD-L1 inhibitors in advanced colorectal cancer: a meta-analysis of randomized controlled trials

Zhenzi Wang  1 , Yuan Liu  1 , Kedi Wang  1 , Liyan Ma  2
Affiliations
Meta-Analysis

Efficacy and safety of PD-1 and PD-L1 inhibitors in advanced colorectal cancer: a meta-analysis of randomized controlled trials

Zhenzi Wang et al. BMC Gastroenterol. .

Abstract

Background: PD-1 and PD-L1 inhibitors have emerged as promising therapies for advanced colorectal cancer (CRC), but their efficacy and safety profiles require further evaluation. This meta-analysis aims to assess the efficacy and safety of PD-1/PD-L1 inhibitors in this patient population.

Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines, with data sourced from PubMed, Embase, CENTRAL, Web of Science, and CNKI up to August 3, 2024. Nine randomized controlled trials (RCTs) involving 1680 patients were included. The primary outcomes were overall survival (OS), progression-free survival (PFS) and objective response rate (ORR), while safety was assessed through adverse events (AEs) and grade ≥ 3 AEs. Effect sizes were calculated using mean differences (MD) and risk ratios (RR) with 95% confidence intervals (CIs).

Results: Overall, the meta-analysis showed that PD-1/PD-L1 inhibitors did not significantly extend OS (MD = 0.86, 95% CI: -0.55, 2.27), but they significantly improved PFS (MD = 2.53, 95% CI: 0.92, 4.15). Additionally, PD-1/PD-L1 inhibitors did not significantly increase the ORR compared to controls (RR = 1.19, 95% CI: 0.99, 1.44). In terms of safety, PD-1/PD-L1 inhibitors did not significantly increase the incidence of overall AEs. Subgroup analysis further indicated that PD-1 inhibitors significantly improved OS (MD = 1.24, 95% CI: 0.20, 2.29) and PFS (MD = 6.27, 95% CI: 0.56, 11.97), while PD-L1 inhibitors did not have a significant impact on these outcomes. Additionally, PD-L1 inhibitors were associated with a higher risk of grade ≥ 3 AEs (RR = 1.29, 95% CI: 1.07, 1.57), a risk not observed with PD-1 inhibitors.

Conclusion: PD-1 inhibitors significantly improve PFS and OS in advanced CRC, making them a preferable option over PD-L1 inhibitors, which show limited efficacy and a higher risk of severe AEs. These findings support prioritizing PD-1 inhibitors in clinical practice for this patient group, while caution is warranted with PD-L1 inhibitors due to their safety concerns.

Trial registration: PROSPERO (CRD42024611696).

Keywords: Adverse events; Colorectal cancer; Immunotherapy; Meta-analysis; PD-1; PD-L1.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate: This is a systematic review and meta-analysis, ethics approval and consent to participate are not applicable. Consent for publication: Not applicable. The manuscript does not include the participant's identification image or other personal or clinical details. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
PRISMA Flow diagram of the search process for studies. RCT randomized controlled trials
Fig. 2
Fig. 2
Forest plot of the efficacy of PD-1/PD-L1 inhibitors in advanced CRC (a, OS; b, PFS; c, ORR). OS, Overall Survival; PFS, Progression-Free Survival; ORR, Objective Response Rate
Fig. 3
Fig. 3
Forest plot of the safety of Colorectal cancer (a, AEs; b, grade ≥ 3 AEs). AEs, adverse events
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Xu L, Zhao J, Li Z, Sun J, Lu Y, Zhang R, et al. National and subnational incidence, mortality and associated factors of colorectal cancer in China: a systematic analysis and modelling study. J Glob Health. 2023;13: 04096. - PMC - PubMed
    1. Morgan E, Arnold M, Gini A, Lorenzoni V, Cabasag CJ, Laversanne M, et al. Global burden of colorectal cancer in 2020 and 2040: incidence and mortality estimates from GLOBOCAN. Gut. 2023;72(2):338–44. - PubMed
    1. Shinji S, Yamada T, Matsuda A, Sonoda H, Ohta R, Iwai T, et al. Recent advances in the treatment of colorectal cancer: a review. J Nippon Med Sch = Nippon Ika Daigaku zasshi. 2022;89(3):246–54. - PubMed
    1. Haller DG. Update on chemotherapy for advanced colorectal cancer. Oncology (Williston Park). 2001;15(3 Suppl 5):11–5. - PubMed
    1. Adebayo AS, Agbaje K, Adesina SK, Olajubutu O. Colorectal cancer: disease process, current treatment options, and future perspectives. Pharmaceutics. 2023;15(11):2620. - PMC - PubMed

MeSH terms

Substances