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
. 2022 Jan;89(1):1-9.
doi: 10.1007/s00280-021-04375-2. Epub 2021 Nov 25.

Correlation between immune-related adverse events and the efficacy of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: systematic review and meta-analysis

Qian Zhang  1   2   3 , Wei Wang  1   2   3 , Qi Yuan  1   2   3 , Li Li  1   2   3 , Yu-Chao Wang  1   2   3 , Chuan-Zhen Chi  1   2   3 , Chun-Hua Xu  4   5   6
Affiliations
Free PMC article
Meta-Analysis

Correlation between immune-related adverse events and the efficacy of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: systematic review and meta-analysis

Qian Zhang et al. Cancer Chemother Pharmacol. 2022 Jan.
Free PMC article

Abstract

Objective: Anti-programmed cell death-1 and programmed cell death ligand-1 (PD-1/PD-L1) inhibitors have been proved to have a significant clinical efficacy in the treatment of non-small cell lung cancer (NSCLC). Many studies have demonstrated that immune-related adverse events (irAEs) are significantly correlated with clinical efficacy, but the results are not consistent. This meta-analysis aimed to evaluate the associations between irAEs and efficacy.

Methods: Comprehensive searches were conducted on PubMed and EMBASE database. The HR and 95% CI were used to assess the associations between immune-related adverse events and efficacy of overall survival and progression-free survival. Subgroup analyses were performed based on irAEs type and grade of irAEs. Heterogeneity and publication bias were also assessed by Q test, I2, and funnel plot.

Results: Compared with non-irAEs, the development of irAEs was significantly improved PFS and OS (PFS: HR = 0.55, 95% CI = 0.51-0.60, p < 0.001; OS: HR = 0.74, 95% CI = 0.68-0.81, p < 0.001). In the subgroup analyses, the occurrence of endocrine irAEs, gastrointestinal irAEs, skin lesions and low-grade irAEs was also significantly correlated with the efficacy. Additionally, the association between severe-grade irAEs and survival benefits on PFS was significant, but not on OS.

Conclusions: The results indicated that the occurrence of irAEs was significantly associated with a better efficacy in the treatment of NSCLC, especially endocrine, gastrointestinal, skin and low-grade irAEs.

Keywords: Efficacy; Immune-related adverse event; Inhibitor; Non-small cell lung cancer; PD-1; PD-L1.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest in this work.

Figures

Fig. 1
Fig. 1
Flowchart and the detailed process of eligible studies
Fig. 2
Fig. 2
Forest plot of immune-related adverse event development associated with PFS. The diamond represents the summary HR and 95% CI
Fig. 3
Fig. 3
Forest plot of immune-related adverse event development associated with OS. The diamond represents the summary HR and 95% CI
Fig. 4
Fig. 4
Funnel plot for the publication bias (A) PFS. (B) OS. Each point represents a separate study for the indicated association
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Mok TSK, Wu YL, Kudaba I, et al. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019;393(10183):1819–1830. - PubMed
    1. Vokes EE, Ready N, Felip E, et al. Nivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases. Ann Oncol. 2018;29(4):959–965. - PubMed
    1. Hellmann MD, Ciuleanu TE, Pluzanski A, et al. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med. 2018;378(22):2093–2104. - PMC - PubMed
    1. Weber JS, Kahler KC, Hauschild A. Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol. 2012;30(21):2691–2697. - PubMed
    1. Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American society of clinical oncology clinical practice guideline. J Clin Oncol. 2018;36(17):1714–1768. - PMC - PubMed

Publication types

MeSH terms

Substances