Sequential transarterial radioembolization and atezolizumab plus bevacizumab improves survival in advanced hepatocellular carcinoma

Abstract Background Yttrium-90 transarterial radioembolization (TARE) combined with immune checkpoint inhibitors has been investigated as a potential therapeutic strategy for advanced hepatocellular carcinoma (HCC); however, evidence supporting its addition to current standard systemic therapy remains limited. We aimed to compare clinical outcomes in patients with advanced HCC treated with TARE followed by atezolizumab plus bevacizumab (TARE–Atezo/Bev) and Atezo/Bev alone. Materials and methods This retrospective cohort study included systemic therapy-naïve patients with advanced HCC treated with Atezo/Bev alone or TARE–Atezo/Bev at a single tertiary hospital between 2018 and 2025. Baseline characteristics were adjusted using propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). The primary outcome was overall survival (OS), and the secondary outcome was progression-free survival (PFS). Results A total of 156 eligible patients were enrolled, including 93 in the Atezo/Bev group and 63 in the TARE–Atezo/Bev group. In the unmatched cohort, median OS was significantly longer in the TARE–Atezo/Bev group than in the Atezo/Bev group (14.1 vs 6.4 months; hazard ratio=0.43, 95% confidence interval = 0.29–0.63; p < 0.001), with consistent results after PSM ( p = 0.01) and IPTW ( p < 0.001). Although PFS was comparable between groups in the overall cohort, patients with Child–Pugh class A (OS: 14.6 vs 7.1 months; PFS: 7.7 vs 6.3 months) or ALBI grade 1 (OS: 21.4 vs 8.3 months; PFS: 8.1 vs 5.7 months) had significantly longer OS and PFS in the TARE–Atezo/Bev group, with similar results after adjustment. Conclusions Sequential TARE–Atezo/Bev may improve survival compared with Atezo/Bev alone in patients with advanced HCC and well-preserved liver function. Key Points Question The survival benefit of yttrium-90 TARE followed by Atezo/Bev compared with Atezo/Bev alone remains uncertain given limited evidence in advanced HCC . Findings TARE followed by Atezo/Bev was associated with significantly longer OS than Atezo/Bev alone, with both OS and PFS improved in patients with advanced HCC and preserved liver function . Clinical relevance Sequential TARE followed by Atezo/Bev may offer a survival advantage in selected patients with advanced HCC, supporting the integration of locoregional and systemic therapies .