Early hepatic decompensation is associated with mortality in patients with HCC treated with atezolizumab plus bevacizumab or durvalumab plus tremelimumab.

BACKGROUND: This study investigates the incidence and impact of early clinical hepatic decompensation (eCHD) on overall survival (OS) in patients with hepatocellular carcinoma (HCC) treated with immune-based therapies. METHODS: A retrospective analysis using TriNetX data included patients with HCC receiving atezolizumab plus bevacizumab (AB) or tremelimumab plus durvalumab (STRIDE) as their first recorded systemic treatment in the database. Primary outcomes were eCHD incidence and its association with OS. Secondary objectives included comparing baseline characteristics according to eCHD occurrence and evaluating outcomes for each treatment regimen by direct comparison and after propensity-score matching (PSM). RESULTS: Among 1,553 patients (1,246 AB and 307 STRIDE), eCHD occurred in 31% of each cohort and most commonly presented as ascites (variceal bleeding: 13.5% with AB vs. 10.5% with STRIDE). Patients with eCHD had worse baseline liver function and shorter median OS than patients without eCHD (AB: 5.5 vs. 16.2 months; STRIDE: 5.2 vs. 13.6 months), and the associations remained statistically significant after PSM for albumin and bilirubin. Among patients with eCHD, no statistically significant difference in OS was observed between treatment cohorts; however, this comparison should be interpreted cautiously. In the AB cohort, patients meeting the treatment-based surrogate definition of early progression had a significantly lower hazard of death than patients with eCHD (early progression versus eCHD; reference group: eCHD; HR 0.59, 95% CI 0.46-0.75, p=0.0002). In the smaller STRIDE cohort, the direction of the association was similar but did not reach statistical significance (early progression versus eCHD; reference group: eCHD; HR 0.58, 95% CI 0.30-1.12). These comparisons were exploratory because early progression was defined using a treatment-based surrogate. CONCLUSIONS: eCHD was associated with poor OS in patients with HCC treated with AB or STRIDE. The association remained statistically significant after matching for albumin and bilirubin, although residual confounding cannot be excluded.