Endocrine Immune-Related Adverse Events Are Independent Predictors of Survival in Patients with Lung Cancer

Cancers (Basel). 2024 May 1;16(9):1764. doi: 10.3390/cancers16091764.

Abstract

Lung cancer (LC) is a serious health problem worldwide. Survival outcomes have improved over time due to the widespread use of novel therapeutic agents, including immune checkpoint inhibitors (ICIs). Endocrine immune-related adverse events (e-irAEs) are common in LC patients treated with ICIs. We performed a retrospective study of patients with LC who received treatment with ICIs at a tertiary referral center between January 2014 and October 2023. In total, 983 LC patients were included in the study. E-irAEs presented at a median time of 4.1 months and included hypothyroidism (15.6%), hyperthyroidism (4.3%), adrenal insufficiency (0.4%), hypophysitis (0.4%), and diabetes mellitus (0.2%). These toxicities were not related to the duration of treatment or the type of ICIs. Most (97.6%) e-irAEs were mild (grade 1-2). Median overall survival (OS) was higher in LC patients who experienced e-irAEs (31.6 months) compared to those who did not (10.8 months). The difference remained statistically significant in the 3-month (HR: 0.42) and 6-month landmark analysis (HR: 0.51). The OS advantage was observed in both patients with NSCLC (HR: 0.36) and SCLC (HR: 0.27). Additional research is needed to validate the role of e-irAEs as an independent predictor of survival outcomes in patients with LC.

Keywords: CTLA-4; PD-1; PD-L1; diabetes mellitus; endocrine toxicity; immune checkpoint inhibitors; immune-related adverse events; non-small-cell lung cancer; pituitary disorders; small-cell lung cancer; thyroid disorders.

Grants and funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.