Immunotherapy in gastrointestinal cancers with pre-existing autoimmune disorders.

Abstract

e14662 Background: The use of immunotherapy (IT) in patients with gastrointestinal cancers (GIC) with pre-existing autoimmune disorders (AID) presents a challenge, balancing survival benefits against AID exacerbation risks. This study evaluates overall survival in patients with GIC treated with IT versus those who were not. Methods: A retrospective cohort analysis using a global real-world clinical data platform was conducted, including de-identified patient records. Two cohorts were compared for each GIC: patients with GIC (esophageal, gastric, colorectal (CRC)) and pre-existing AID (inflammatory bowel disease, connective tissue diseases, dermato/polymyositis, sarcoidosis, or psoriasis) treated with ICIs (nivolumab or pembrolizumab) and those not treated with ICIs. The primary outcome was time to death. Propensity score matching (PSM) adjusted for age, sex, race, ethnicity, comorbidities, cancer stage, and prior treatments (surgery, chemotherapy, targeted therapy, and radiation). Results: Before matching, the non-ICI group included 35,826 CRC, 4,729 esophageal, and 5,519 gastric, while the IT group consisted of 656 CRC, 383 esophageal, and 344 gastric. After PSM, we had 635 CRC, 381 esophageal, and 340 gastric. Kaplan-Meier analysis for CRC showed a median survival of 5.64 years in the IT group vs 8.87 years in the non-IT group (log-rank p = 0.001), with a 37% higher risk of death in the IT group (HR 1.37, 95% CI: 1.14–1.63). Similar trends were observed in esophageal and gastric cancers, though not statistically significant. Conclusions: IT in GIC patients with pre-existing AID was associated with significantly worse CRC survival, with similar trends in other luminal GIC. These findings highlight the need for individualized decision-making when prescribing IT in these patients. Cox regression analysis of IT use in GIC with time to death as the outcome. IT use in GI cancers Cox regression analysis after PSM * Log-rank test HR (95% CI) p-value Esophageal cancer 1.14 (0.92,1.41) 0.228 Gastric cancer 1.12 (0.90,1.40) 0.304 Colorectal cancer 1.37 (1.14,1.63) 0.001 IT: Immunotherapy, GI: Gastrointestinal, PSM: Propensity Score Matching, HR: Hazard Ratio, CI: Confidence Interval.