Comparative survival and long-term gastrointestinal outcomes of ipilimumab/nivolumab vs durvalumab/tremelimumab in unresectable hepatocellular carcinoma: A propensity-matched real-world analysis.

Abstract

e16221 Background: The FDA approval of Nivolumab plus Ipilimumab (Ipi/Nivo) as a first-line (1L) therapy for unresectable hepatocellular carcinoma (HCC), following the CheckMate 9DW trial, has expanded the dual-immunotherapy landscape alongside Durvalumab plus Tremelimumab (Durva/Trem). However, direct comparative data regarding long-term gastrointestinal (GI) complications in a real-world setting remain scarce. This real-world analysis provides the first comparative assessment of survival and GI outcomes between these two treatment regimens. Methods: Using the TriNetX Global Federated Database, we identified patients aged 18-90 years with unresectable HCC who were treated with 1L Ipi/Nivo (Cohort A) or Durva/Trem (Cohort B). Cohorts were propensity score-matched (1:1) using the nearest-neighbor algorithm for demographics, hepatic comorbidities, and Child's Pugh Score. The primary endpoint was all-cause mortality. Secondary endpoints were the incidence of GI complications, including GI bleed, spontaneous bacterial peritonitis (SBP), hepatic encephalopathy (HE), colitis, portal vein thrombosis (PVT), ascites, and jaundice. Outcomes were assessed at 1-, 2-, and 3-year post-index. Kaplan–Meier curves assessed cumulative incidence, while Cox proportional hazards models estimated adjusted hazard ratios (HRs, 95% CI). Results: After matching, 580 patients were included per cohort. Median follow-up was 3 years for Ipi/Nivo and Durva/Trem. Demographics were similar between cohorts (mean age 64, 22% Female, 78% Male, 59% White, 13% Black). There was no significant difference in all-cause mortality between Ipi/Nivo vs Durva/Trem at 1 year [114/574 (19.9%) vs 124/566 (21.9%); HR: 0.807 (0.625-1.041)], 2 years [188/574 (32.7%) vs 164/566 (28.9%); HR: 0.937 (0.760-1.156)], and 3 years [235/574 (40.9%) vs 181/566 (31.9%); HR: 1.025 (0.844-1.245)]. Long term GI outcomes at 3 years showed a 68% reduction in HE [HR: 0.321 (0.222-0.465)], a 34% reduction in PVT [0.661 (0.496-0.880)], and a 32% reduction in ascites [HR: 0.678 (0.550-0.835)], all favoring Ipi/Nivo. No significant differences were observed between Ipi/Nivo and Durva/Trem for GIB, SBP, colitis, and jaundice. Conclusions: In this multicenter, real-world analysis, 1L treatment with Ipi/Nivo and Durva/Trem demonstrated similar survival benefits at 1, 2, and 3 years. However, Ipi/Nivo demonstrated a significantly superior GI safety profile, showing reductions in HE, PVT, and ascites compared to Durva/Trem at 3 years. These results suggest that while both dual-immunotherapy regimens offer similar survival benefits, Ipi/Nivo appear to be associated with a more favorable long-term GI safety profile. Future prospective head-to-head comparisons are warranted to better understand these associations.