Age stratified IRAEs with immune checkpoint inhibitors in patients with metastatic gastric and colorectal cancer: Multicenter retrospective propensity matched analysis.

Abstract

832 Background: Immune checkpoint inhibitors (ICIs) have emerged as a promising treatment modality for metastatic gastric, gastroesophageal, and colorectal cancers. They can cause immune-related adverse events (irAEs), which can be severe or life-threatening. Elderly patients (≥65 years) are underrepresented in clinical trials and may be at increased risk for toxicity due to altered immune function and comorbidities. We aimed to analyze the real-world irAEs patterns across age groups and assess outcomes such as overall survival. Methods: We conducted a multicenter retrospective study using the TrinetX database network, a federated electronic medical record network. Statistical analysis is performed on the TrinetX research platform. Adults with metastatic gastric, gastroesophageal, and colorectal cancer were included in the final analysis. Immunotherapy agents included are: Pembrolizumab, Nivolumab, Durvalumab, Ipilimumab, and Atezolizumab. The entire cohort was divided into two groups (> 65 years of age and ≤65 years of age). Subsequently, 1:1 propensity matching (PSM) was done, and overall survival was calculated. Cox regression analysis was done to derive the odds of each IRAE (Autoimmune thyroiditis, hypophysitis, adrenalitis, hepatitis, pneumonitis, thrombocytopenia, vitiligo, skin rash) in patients of > 65 years of age. Results: A total of 13,199 patients with metastatic disease were included, and 65.6% (n=8660) were adults of more than 65 years of age. 71.5% (n=9444) were whites and 36.6% (n=4832) were females. The mean age was 71.8 years (±10.9) in the > 65 years group, and 50.8 years (±8.9) in the ≤65 years group. 75.9% (n=10,028) had exposure to platinum-based chemotherapy. Immunotherapeutic agents included Pembrolizumab (n=6683, 50.6%), Nivolumab (n=5371, 40.6%), Ipilimumab (n=915, 6.9%), Atezolizumab (n=681, 5.1%), and Durvalumab (n=507, 3.8%). After 1:1 PSM, 3843 patients were included in each cohort. There was no significant difference in the median overall survival between the two groups (15.6 months vs 16.7 months, p=0.783). The propensity-matched sample did not reveal any significant difference in thyroiditis, adrenalitis, pneumonitis, thrombocytopenia, vitiligo, skin rash, or hepatitis (p>0.05). However, there was a significantly higher incidence of hypophysitis in patients with more than 65 years of age (0.7% vs 0.3%, p=0.005). Conclusions: This study will provide valuable insights into age-related differences in immune-related toxicity and outcomes among patients with metastatic gastric, gastroesophageal, and colorectal cancers treated with ICIs. The findings may inform risk-benefit discussions, guide supportive care planning, and prompt further prospective research into geriatric-specific immune oncology care with specific consideration of autoimmune hypophysitis.