Translational lung cancer research · 2025
Endocrine immune-related adverse events in advanced lung cancer patients receiving immune checkpoint inhibitors: incidence, predictors and outcomes.
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Liu Yi, Zhang Jiarui, Yang Linhui, Gan Jiadi, Zhang Huohuo, Qi Qi, Fang Wanqin, Zhu Junyi, Xu Rui, Hu Xianya, Xie Yufang, Liu Sha, Li Weimin, Liu Dan
Аннотация
BACKGROUND: Immune checkpoint inhibitors (ICIs) have markedly improved outcomes in lung cancer but may lead to immune-related adverse events (irAEs). Among them, endocrine irAEs (e-irAEs) are frequent, yet their risk factors and prognostic implications remain unclear. This study aimed to investigate the incidence, predictors, and clinical outcomes of e-irAEs in patients with advanced lung cancer receiving ICIs.
METHODS: In this single-center retrospective cohort study, we analyzed patients with advanced lung cancer who received at least 2 cycles of ICIs from January 2019 to October 2023 at West China Hospital of Sichuan University. Patients were categorized into e-irAE and no e-irAE groups. The cumulative incidence of e-irAE was estimated using the Aalen-Johansen method, accounting for death as a competing risk. Risk factors for e-irAEs were assessed using Fine-Gray subdistribution hazard model and logistic regression, while a time-dependent Cox model was employed to evaluate the impact of e-irAEs on progression-free survival (PFS) and overall survival (OS).
RESULTS: Our analysis included 603 patients in total, 60 (10.0%) developed e-irAEs, predominantly hypothyroidism (73.3%) and thyrotoxicosis (23.3%), with a median onset of 4.0 months. During follow-up, 261 (43.3%) patients died. Female sex [subdistribution hazard ratio (SHR), 2.27; 95% confidence interval (CI), 1.23-4.21; P=0.009], lung metastasis (SHR, 1.79; 95% CI, 1.07-3.02; P=0.03), elevated thyroid stimulating hormone (TSH) (SHR, 1.04; 95% CI, 1.02-1.06; P<0.001), increased eosinophil count (SHR, 1.66; 95% CI, 1.32-2.10; P<0.001), and objective response (SHR, 2.23; 95% CI, 1.25-3.97; P=0.007) were associated with higher risk of e-irAE development. Patients with e-irAEs had superior OS (median 42.0 vs. 27.0 months; P=0.04) and a trend toward improved PFS (median PFS 14.0 vs. 12.0 months; P=0.08). Time-dependent cox analysis indicated that e-irAE was associated with a favorable trend in both PFS [hazard ratio (HR), 0.77; 95% CI, 0.50-1.19; P=0.24] and OS (HR, 0.84; 95% CI, 0.52-1.36; P=0.48).
CONCLUSIONS: e-irAEs occurred in approximately 10% of advanced lung cancer patients receiving ICIs. Predictors of e-irAE development included female sex, lung metastasis, increased eosinophil count, elevated TSH, and objective response to ICIs. Patients with e-irAE occurrence tended to have a favorable survival outcome.
METHODS: In this single-center retrospective cohort study, we analyzed patients with advanced lung cancer who received at least 2 cycles of ICIs from January 2019 to October 2023 at West China Hospital of Sichuan University. Patients were categorized into e-irAE and no e-irAE groups. The cumulative incidence of e-irAE was estimated using the Aalen-Johansen method, accounting for death as a competing risk. Risk factors for e-irAEs were assessed using Fine-Gray subdistribution hazard model and logistic regression, while a time-dependent Cox model was employed to evaluate the impact of e-irAEs on progression-free survival (PFS) and overall survival (OS).
RESULTS: Our analysis included 603 patients in total, 60 (10.0%) developed e-irAEs, predominantly hypothyroidism (73.3%) and thyrotoxicosis (23.3%), with a median onset of 4.0 months. During follow-up, 261 (43.3%) patients died. Female sex [subdistribution hazard ratio (SHR), 2.27; 95% confidence interval (CI), 1.23-4.21; P=0.009], lung metastasis (SHR, 1.79; 95% CI, 1.07-3.02; P=0.03), elevated thyroid stimulating hormone (TSH) (SHR, 1.04; 95% CI, 1.02-1.06; P<0.001), increased eosinophil count (SHR, 1.66; 95% CI, 1.32-2.10; P<0.001), and objective response (SHR, 2.23; 95% CI, 1.25-3.97; P=0.007) were associated with higher risk of e-irAE development. Patients with e-irAEs had superior OS (median 42.0 vs. 27.0 months; P=0.04) and a trend toward improved PFS (median PFS 14.0 vs. 12.0 months; P=0.08). Time-dependent cox analysis indicated that e-irAE was associated with a favorable trend in both PFS [hazard ratio (HR), 0.77; 95% CI, 0.50-1.19; P=0.24] and OS (HR, 0.84; 95% CI, 0.52-1.36; P=0.48).
CONCLUSIONS: e-irAEs occurred in approximately 10% of advanced lung cancer patients receiving ICIs. Predictors of e-irAE development included female sex, lung metastasis, increased eosinophil count, elevated TSH, and objective response to ICIs. Patients with e-irAE occurrence tended to have a favorable survival outcome.