Radioembolization plus Immune Checkpoint Inhibitor Therapy Compared with Radioembolization plus Tyrosine Kinase Inhibitor Therapy for the Treatment of Hepatocellular Carcinoma

Purpose: To investigate if combination therapy with immune checkpoint inhibitor (ICI) and yttrium-90 (⁹⁰Y) radioembolization results in superior outcomes than those yielded by tyrosine kinase inhibitor (TKI) therapy and ⁹⁰Y for the treatment of intermediate- to advanced-stage hepatocellular carcinoma (HCC). Methods: A retrospective review of patients presented at an institutional multidisciplinary liver tumor board between January 1, 2012 and August 1, 2023 was conducted. In total, 44 patients with HCC who underwent ⁹⁰Y 4 weeks within initiation of ICI or TKI therapy were included. Propensity score matching was conducted to account for baseline demographic differences. Kaplan–Meier analysis was used to compare median progression-free survival (PFS) and overall survival (OS), and univariate statistics identified disease response and control rate differences. Duration of imaging response was defined as number of months between the first scan after therapy and the first scan showing progression as defined by modified Response Evaluation Criteria in Solid Tumors (mRECIST) or immune Response Evaluation Criteria in Solid Tumors (iRECIST). Adverse events were analyzed per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: Patients in the ⁹⁰Y+ICI therapy group had better objective response rates (ORRs) (89.5% vs 36.8%; P < .001) and disease control rates (DCRs) (94.7% vs 63.2%; P < .001) by mRECIST and iRECIST (ORR: 78.9% vs 36.8%; P < .001; DCR: 94.7% vs 63.2%; P < .001). Median PFS (8.3 vs 4.1 months; P = .37) and OS (15.8 vs 14.3 months; P = .52) were not statistically different. Twelve patients (63.1%) in the ⁹⁰Y+TKI group did not complete systemic therapy owing to adverse effects compared with 1 patient (5.3%) in the ⁹⁰Y+ICI group (P < .001). Grade 3/4 adverse events were not statistically different (⁹⁰Y+TKI: 21.1%; ⁹⁰Y+ICI: 5.3%; P = .150). Conclusions: Patients with HCC who received ⁹⁰Y+ICI had better imaging response and fewer regimen-altering adverse events than those who received ⁹⁰Y+TKI. No significant combination therapy adverse events were attributable to radioembolization.