Immunotherapy and Transarterial Radioembolization Combination Treatment for Advanced Hepatocellular Carcinoma

INTRODUCTION: The efficacy and safety of combined immunotherapy and transarterial radioembolization (TARE) were suggested in preclinical and early-phase trials, but these were limited by small sample sizes. We sought to compare the efficacy of combined therapy and immunotherapy alone in patients with advanced hepatocellular carcinoma (HCC). METHODS: The National Cancer Database was used to identify patients with advanced HCC diagnosed between January 1, 2017, and December 31, 2019. We included patients who received combined therapy or immunotherapy alone as first-line treatment. Multivariable logistic regression was conducted to determine predictors of combined therapy. Kaplan-Meier and Cox regression approaches were used to identify predictors of overall survival and to compare hazards of mortality between the patients who received combined therapy and immunotherapy alone. RESULTS: Of 1,664 eligible patients with advanced-stage HCC, 142 received combined TARE/immunotherapy and 1,522 received immunotherapy alone. Receipt of combination therapy was associated with care at an academic center and inversely associated with racial/ethnic minority status (Hispanic and Black individuals). The median overall survival was significantly higher in the combination group than in the immunotherapy alone group (19.8 vs 9.5 months). In multivariable analysis, combined therapy was independently associated with reduced mortality (adjusted hazard ratio 0.50, 95% confidence interval: 0.36-0.68, P < 0.001). Results were consistent across subgroups and in sensitivity analyses using propensity score matching and inverse probability of treatment weighting. DISCUSSION: The combination of TARE and immunotherapy was associated with improved survival compared with immunotherapy alone in patients with advanced-stage HCC. Our findings underly the importance of large clinical trials evaluating combination therapy in these patients.