The association between toxicity and efficacy of immune checkpoint inhibitors in older adults with NSCLC
Creators: name: Rong, Yiran
name: Ramachandran, Sujith
name: Bhattacharya, Kaustuv
name: Yang, Yi
name: Earl, Sally
name: Chang, Yunhee
name: Bentley, John P
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Space Science
subject: Medicine
subject: Pharmacology
subject: Environmental Sciences not elsewhere classified
subject: Chemical Sciences not elsewhere classified
subject: Sociology
subject: FOS: Sociology
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Cancer

description: <b>Aim:</b> 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. <b>Methods:</b> 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. <b>Results &amp; conclusion:</b> 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. 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. An increasing number of studies using real-world data show that the development of irAEs is associated with improved clinical outcomes; however, many of them failed to appropriately account for immortal time bias. Using a large database of US Medicare beneficiaries, our study focused on older patients (aged ≥65 years) and assessed the association between irAE occurrence and health outcomes. We found that older NSCLC patients with ICI-induced irAEs had higher risk of death as compared with who did not develop. Older patients who had irAEs were also more likely to discontinue their ICI treatment. The occurrence of pneumonitis, arrhythmia, AKI, hepatitis and colitis can lead to worse health outcomes, while hypothyroidism and dermatologic irAEs were found to be associated with improved outcomes. Our study findings suggest that older adults should be closely monitored for the development of irAEs following initiation of ICI treatment to prevent life-threatening outcomes.