Efficacy and safety of atezolizumab and bevacizumab with or without transarterial chemoembolization as first-line therapy for advanced hepatocellular carcinoma: An international multicenter real-world study.

4105 Background: Transarterial chemoembolization (TACE) combined with immunotherapy and targeted therapy provides a promising therapy for advanced hepatocellular carcinoma (HCC).This study aimed to compare the efficacy and safety of atezolizumab and bevacizumab combined with (TACE-Ate-Bev) or without TACE (Ate-Bev) as first-line treatment for advanced HCC. Methods: This international multicenter, retrospective study included 311 advanced HCC cases administered TACE-Ate-Bev (n = 152) or Ate-Bev (n = 159). Inverse probability of treatment weighting (IPTW) was employed to minimize bias. Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were observed. Results: The TACE-Ate-Bev group demonstrated significantly improved OS (26.8 [95% CI 23.1-NA] vs. 14.9 months [95% CI 11.4-19.9]; hazard ratio [HR] = 2.66 [95% CI 1.87-3.77], p < 0.0001) and PFS (16.0 months [95% CI 12.8-17.8] vs. 6.5 months [95% CI 5.4-7.6]; HR = 2.50 [95% CI 1.90–3.28], p < 0.0001) compared to the Ate-Bev group, especially across BCLC stage B (mOS: NA [95% CI 23.5-NA] vs. 15.6 months [95% CI 11.4-NA], p < 0.0001; mPFS: 16.9 months [95% CI 16.2-NA] vs. 6.7 months [95% CI 5.7-10.9], p < 0.0001) and BCLC stage C (mOS: 25.2 months [95% CI 19.7-NA] vs. 14.3 months [95% CI 10.1-20.5], p = 0.00018; mPFS: 12.8 months [95% CI 11.3-17.0] vs. 6.5 months [95% CI 5.0-7.7], p < 0.0001) disease. The superior efficacy of TACE-Ate-Bev indicated same trends after IPTW adjustment. Grade 3 or 4 AEs were observed in 36 patients (24.3%) in the TACE-Ate-Bev group and 34 (21.4%) in the Ate-Bev group. There was no statistically significant difference in the proportion of gastrointestinal bleeding between the TACE-Ate-Bev and Ate-Bev groups (9.9% vs. 10.1%, p = 0.954). Notably, patients with portal hypertension, portal vein tumor thrombus vp3-4, extrahepatic metastasis or Child-Pugh grade B exhibited improved OS and PFS in the TACE-Ate-Bev group versus the Ate-Bev group. Conclusions: TACE-Ate-Bev significantly improves OS and PFS with acceptable toxicity compared to Ate-Bev as first-line therapy for advanced HCC.