Atezolizumab plus Bevacizumab Versus Durvalumab plus Tremelimumab in Unresectable Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Multicenter Retrospective Study

Abstract

Background: The optimal ICI-based systemic treatment for unresectable hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), particularly main portal vein invasion, remains unclear. We compared atezolizumab plus bevacizumab (ATZ/BEV) and durvalumab plus tremelimumab (DUR/TRE) according to PVTT extent. Methods: This multicenter retrospective study included 1,015 patients treated with ATZ/BEV and 186 treated with DUR/TRE. Treatment response, progression-free survival (PFS), overall survival (OS), and safety were compared between groups. Subgroup analyses were performed according to PVTT extent. Results: In the overall cohort, the objective response rate was comparable between the ATZ/BEV and DUR/TRE groups (31.0% vs. 31.7%, P = 0.86), whereas the disease control rate was significantly higher in the ATZ/BEV (78.4% vs. 62.4%, P < 0.01). Median PFS was significantly longer with ATZ/BEV than with DUR/TRE (6.9 vs. 5.3 months, P = 0.049), whereas median OS was comparable between groups (24.9 vs. 31.0 months, P = 0.72). In subgroup analyses stratified by PVTT extent, PFS and OS were generally comparable in patients with Vp1–Vp3 disease. However, among patients with Vp4 disease, median OS was significantly longer with ATZ/BEV than with DUR/TRE (16.6 vs. 6.1 months; HR, 3.60; 95% CI, 1.33–9.74; P < 0.01). The OS difference in Vp4 disease was attenuated and no longer significant in an 8-week landmark analysis. Conclusions: ATZ/BEV was associated with a longer PFS than DUR/TRE in the overall cohort. In patients with Vp4 PVTT, ATZ/BEV may be associated with favorable survival outcomes; however, these findings should be considered hypothesis-generating and require validation.