SUN-279 - Immune Checkpoint Inhibitor Administration after 11:30 AM Reduces Endocrine Immune-Related Adverse Events in Tyrosine Kinase Inhibitor Combination Therapy

Background:
Tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitors (ICIs) are standard first-line therapies for multiple malignancies, but the impact of ICI administration time points on endocrine adverse events (irAEs) remains unclear. The potential link between endocrine irAEs and survival also warrants exploration.

Objective:
To explore the effect of the average of the first four ICI administration times on new-onset endocrine irAEs and survival in TKI+ICI-treated patients, guiding individualized regimens.

Methods:
This single-center retrospective cohort study included 169 consecutive TKI+ICI-treated patients (Jan 2020-Jun 2023) with normal baseline endocrine function, excluding those with incomplete data or missing ICI administration time. Patients were grouped by a 9:30-14:00 window with half-hour cut-offs. Univariate/multivariate Cox models (adjusted for age, gender, tumor type) analyzed associations between ICI administration time points and prespecified endpoints (new-onset endocrine irAEs, all-cause death); post-hoc analysis explored irAEs-survival association.

Results:
Among patients, 115 were male (68.05%), median age 59.68 (IQR:50.82-68.12), median follow-up 322 days (IQR:163-544). 154 patients (91.12%) had ECOG performance status 0-1; urologic tumors were most common (40.83%). 85 patients (50.30%) developed endocrine irAEs (66 thyroid, 41 glucose metabolism-related, 1 adrenal [excluded from stratification due to small sample size]). Predominant subtypes were isolated thyroid irAEs (n=43) and thyroid-glucose metabolism irAEs (n=22).
Only the cut-off time of 11:30 showed statistical significance. Treatment after 11:30 AM was associated with a significantly lower risk of endocrine irAEs compared to treatment before 11:30 AM (HR=0.588, 95% CI 0.351-0.984, P=0.043). Thyroid irAEs subgroup results were consistent (HR=0.473, 95% CI 0.243-0.918, P=0.027). No significance was seen in the glucose metabolism-related irAEs subgroup at all time points.
Post-hoc analysis revealed that patients who developed new-onset endocrine irAEs had significantly better survival than those without irAEs (HR=0.543, 95% CI 0.302-0.975, P=0.041). ICI administration timing showed no direct correlation with survival.

Conclusion:
The timing of TKI+ICI administration may influence the risk of endocrine irAEs, with treatment after 11:30 AM potentially associated with a lower risk. This suggests that the timing of medication administration could have an impact on toxicity profiles. Further studies are needed to validate these findings and inform individualized treatment strategies.

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