Endocrine adverse events associated with immunotherapy: A retrospective cohort study.

e23387 Background: Immunotherapy (IT) are a cornerstone of cancer therapy but are associated with immune-related adverse events (AEs). Real-world studies often lack a comparative control group, limiting causal inference. We evaluated the incidence & risk of endocrine (Endo) AEs in patients receiving IT versus non-IT therapies. Methods: We conducted a retrospective cohort study of adult cancer patients (n = 5,556) treated between January 2010 & December 2022 within the Cleveland Clinic health system in Ohio. Patients receiving IT were compared with non-IT patients. Anti–PD-1/PD-L1 &/or anti–CTLA-4 agents accounted for 99.9% of IT exposure. Follow-up began at first systemic therapy until Endo-AE, death, or last follow-up. Endo-AEs included hypothyroidism, thyrotoxicosis, hypophysitis, primary adrenal insufficiency, & hyperglycemia. Cumulative incidence rates (CIR) were estimated by first-line IT exposure. Cox models treated IT as a time-dependent covariate. Incidence rates per 100 person-years were calculated using the Poisson distribution. Results: Among 5,556 patients,1,291 (23%) received first-line IT & 948 (17%) received second-line IT. Median age was 66 years; 38% were female & 87% White. The cohort was predominantly composed of patients with advanced lung cancer, including stage IV non–small cell lung cancer (29%) & advanced small cell lung cancer (11%). Other common malignancies included esophageal/gastric cancers (stages II–III, 14%; stage IV, 11%), bladder, kidney, endometrial, & other advanced solid tumors. Median follow up of 14 months (CI: 6-34), a total of 120 endocrine-AE were observed (Table 1), including hypothyroidism (n = 84; IT: 51 vs non-IT: 33), hyperglycemia (n = 14; IT: 8 vs non-IT: 6), primary adrenal insufficiency (n = 13; IT: 10 vs non-IT: 3), thyrotoxicosis (n = 7; IT: 4 vs non-IT: 3), & hypophysitis (n = 4; IT: 3 vs non-IT: 1). Among hypothyroidism cases, 76% were CTCAE grade 2; 35% required hormone replacement, 6% required treatment discontinuation, 1% were central, & 32% subclinical. Conclusions: IT is associated with a significantly increased incidence of Endo-AEs that may occur beyond the first year of treatment. Events were predominantly grade 1–2, rarely required immune-modulating therapy, & infrequently resulted in permanent treatment discontinuation, supporting the overall safety of IT with appropriate monitoring. Characteristic IT group (n=1,291) Non-IT group (n=4,265) Endocrine: absolute number of AE 74 46 Endocrine: Incidence rates per 100 person years (95% CI) 0.30 (0.23-0.37) 0.04 (0.03-0.05) Endocrine: 24-month CIR (95% CI) 8.0 (6.1-9.8) 1.2 (08-1.6) Endocrine: Time dependent Cox HR 13.7 (8.6-22), P<0.001 Ref Hypothyroidism: absolute number of AE 51 33 Hypothyroidism: Incidence rates per 100 person years (95% CI) 0.20 (0.15-0.26) 0.03 (0.02-0.04) Hypothyroidism: 24-month CIR (95% CI) 5.6 (4-7) 0.7 (0.4-1) Hypothyroidism Time dependent Cox HR11.8 (6.9-20), P<0.001 Ref