The association between toxicity and efficacy of immune checkpoint inhibitors in older adults with NSCLC

Immunotherapy. 2024;16(16-17):1057-1068. doi: 10.1080/1750743X.2024.2394382. Epub 2024 Sep 13.

Abstract

Aim: This cohort study evaluated the association between immune checkpoint inhibitors (ICIs)-induced immune-related adverse events (irAEs) and mortality as well as ICI discontinuation among older adults with NSCLC.Methods: 2007-2019 Surveillance, Epidemiology and End Results-Medicare linked database was used and survival analysis with time-varying exposure of irAEs was applied to estimate the associations.Results & conclusion: A total of 8,175 individuals were included, with 46.8% of whom developed an irAE. Cox regression models showed the occurrence of any irAEs was associated with increased risk of mortality (HR: 1.73, 95% CI: 1.63-1.82) and treatment discontinuation (HR: 1.87, 95% CI: 1.78-1.97). Some variability was observed in the effect on the two outcomes depending on the type of irAE.

Keywords: immune checkpoint inhibitors; immune-related adverse events; non-small-cell lung cancer; older adults; survival.

Plain language summary

A few studies have suggested that certain adverse events related to the immune system (called immune-related adverse events, or irAEs) following treatment of immune checkpoint inhibitors (ICIs) are linked to better clinical outcomes associated with ICI treatment. In contrast, this study of older adults with lung cancer found that patients suffering from irAEs were more likely to die and discontinue ICI treatment. Adverse events such as pneumonitis, arrhythmia, acute kidney injury, hepatitis and colitis were found to be associated with worse outcomes, while hypothyroidism and dermatologic irAEs were not. To prevent life-threatening outcomes for older adults with lung cancer, it is important to closely monitor for the development of irAEs following the initiation of ICI therapy.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / immunology
  • Carcinoma, Non-Small-Cell Lung* / mortality
  • Cohort Studies
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Female
  • Humans
  • Immune Checkpoint Inhibitors* / adverse effects
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / immunology
  • Male
  • SEER Program
  • United States / epidemiology

Substances

  • Immune Checkpoint Inhibitors