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

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

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Humans
  • Immune Checkpoint Inhibitors / adverse effects*
  • Immune Checkpoint Inhibitors / immunology
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / immunology
  • Progression-Free Survival
  • Treatment Outcome

Substances

  • Immune Checkpoint Inhibitors