OR06-06 Endocrine Adverse Reactions Caused by the Combination of Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors: A Retrospective Cohort Study

Abstract Disclosure: W. Shao: None. K. Yang: None. D. Lu: None. Y. Gao: None. J. Zhang: None. Y. Huang: None. Y. Zhang: None. Background: Tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor (ICI) individually induce endocrine adverse reactions (EARs). However, the clinical characteristics of EARs during combination therapy, except for thyroid dysfunction (TD), remain systematically underexplored, particularly in relation to glucose metabolism disorders (GMD) and adrenal insufficiency (AI). Methods: This retrospective cohort study analyzed EARs in cancer patients receiving TKI+ICI regimens from 2020 to 2023. Longitudinal assessments included thyroid function (TSH/FT4), glycemic metabolism (HbA1C/FBG), and adrenal function (ACTH/cortisol) profiling before and after combination therapy. Multivariable models were used to identify risk factors for EARs and assess the association between EARs and outcomes. Results: The cohort included 319 patients (median age 62.8 years, median follow-up 11.2 months, 68.0% males, 40.4% with urologic neoplasms). Of 147 patients assessed for thyroid function, 97 (66.0%) developed TD, with a median onset of 8.7 weeks. Subclinical hypothyroidism accounted for 67.0% of TD cases. Multivariate logistic regression revealed baseline TSH level (OR 1.69, 95%CI: 1.20-2.39), female (OR 5.61, 95%CI: 1.82-17.27), urinary system tumor (OR 4.68, 95%CI: 1.63-13.37), and 3rd-generation TKI+PD-1 inhibitor (OR 3.18, 95%CI: 1.13-8.96) as independent TD risk factors. Among 196 subjects with glucose data, 49 (25.0%) developed diabetes mellitus (DM), with a median onset of 16.2 weeks. The proportions of overweight patients (BMI≥24kg/m2, 46.9% vs. 30.6%) and patients receiving 2nd-generation TKI+anti-PD-1 inhibitor (53.1% vs. 45.6%) were significantly greater in the DM group compared to control group (P<0.05 for all). AI occurred in 7 male patients (6.7%) out of 105 who underwent adrenal function testing, with a median onset of 31.0 weeks, the majority of cases (5/7) were secondary AI. Multiple EARs occurred in 27 patients, of which 22 had TD+DM, 4 had TD+AI, and 1 had AI+DM. TD appeared prior to DM or AI, while AI developed after DM. Survival analysis revealed TD as an independent predictor of improved overall survival (HR 0.41, 95%CI: 0.22-0.78), whereas DM or AI showed no prognostic association. Conclusions: The main type of TD, GMD and AI associated with combination therapy were hypothyroidism, DM and secondary AI, respectively. The risk factors for different EARs were varied by glands. Only TD was linked to a better prognosis. Presentation: Saturday, July 12, 2025