MON-362 Endocrine Immune-Related Adverse Events in Immune Checkpoint Inhibitor Therapy: Insights Across Cancer Types and Treatment Stages

Abstract Disclosure: A. Khine: None. A. Haslam: None. V. Prasad: None. Z. Quandt: None. Background: Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape, particularly for cancers such as melanoma and non-small cell lung cancer (NSCLC). Despite their efficacy, immune-related adverse events (irAEs), particularly endocrine irAEs, pose significant challenges. Herein, we quantify and compare the incidence of endocrine irAEs across metastatic and adjuvant settings in melanoma and NSCLC. Methods: This cross-sectional analysis reviewed clinical trials supporting FDA approval of ICIs in metastatic and adjuvant settings, with data through December 2024. Trials without data on endocrine irAEs were excluded. Incidence of overall endocrine irAEs, hypophysitis, hypothyroidism, and diabetes were extracted. Cumulative incidence percentages were calculated by dividing the total number of events by the total population size for each treatment context. Subgroup analyses examined specific ICI regimens, including PD-1/PD-LI monotherapy, CTLA-4 inhibitors, and combination therapies (e.g., nivolumab/ipilimumab, chemotherapy). Fisher’s exact test was used to evaluate statistical significance in differences in percentages between treatment contexts. Results:Melanoma: Percentages of overall endocrine irAEs, hypophysitis, and hypothyroidism were all significantly higher in the adjuvant setting compared to the metastatic setting. For example, for PD-1/PD-L1 inhibitors, the percentages in the adjuvant vs metastatic setting were 23.4% vs 10.3% (p <0.001) for overall endocrine irAEs, 1.8% vs 0.6% (p = 0.002) for hypophysitis, and 12.5% vs 8.7% (p <0.001) for hypothyroidism. For CTLA-4 inhibitors, the percentages in the adjuvant vs metastatic setting were 37.5% vs 10% (p <0.001) for overall endocrine irAEs, 14.5% vs 2.9% (p<0.001) for hypophysitis, and 7.9% vs 2.9% (p <0.001) for hypothyroidism. Diabetes showed no clinically significant differences but was limited by low event percentages. NSCLC: Percentages of hypothyroidism were significantly higher in the adjuvant setting compared to the metastatic setting (17.4% vs 8.1%; p <0.001) for PD-1/PD-L1 inhibitors. Percentages were not significantly different for hypophysitis or diabetes. Percentages for overall endocrine irAEs were not available in the adjuvant setting. Conclusion: In melanoma and NSCLC, the incidence of endocrine irAEs varies significantly depending on treatment context and regimen. Further research is needed to better understand these variations and optimize management strategies for endocrine irAEs in ICI-treated patients as the long-term nature of endocrine irAEs may impact patient quality of life more in the adjuvant setting than the metastatic setting. Presentation: Monday, July 14, 2025