Transarterial chemoembolization combined with atezolizumab plus bevacizumab versus transarterial chemoembolization combined with lenvatinib plus sintilimab as first-line therapy for advanced hepatocellular carcinoma.

e16223 Background: Transarterial chemoembolization (TACE) combined with immunotherapy and anti-angiogenic therapy as first-line treatment for advanced hepatocellular carcinoma (HCC) ,demonstrating a promising option. To compare the efficacy and safety of TACE combined with Atezolizumab Plus Bevacizumab (TACE-Ate-Bev) or TACE combined with lenvatinib plus Sintilimab(TACE-Len-Sin) as first-line treatments for advanced HCC. Methods: We assessed overall survival (OS), progression-free survival (PFS), objective response rate(ORR), and adverse events between the TACE-Ate-Bev group (n = 108) and the TACE-Len-Sin group (n = 160) as first-line therapy for advanced HCC. Inverse probability of treatment weighting was employed to minimize bias. Efficacy was evaluated using RECIST 1.1 and mRECIST criteria. Results: After IPTW, the TACE-Ate-Bev group significantly extended the median overall survival (mOS) and median progression-free survival (mPFS) compared to theTACE-Len-Sin group (mOS: 27.9 months vs. 17.03 months, P < 0.001; mPFS: 13.06 months vs. 8.23months, P < 0.001). A higher ORR was observed in TACE-Ate-Bev group, by either RECIST v1.1 or modified RECIST (37.03% vs 33.13%；50.0% vs 33.73%). Grade ≥3 adverse events occurred in 18 patients (16.7%) in TACE-Ate-Bev group and 28 patients (17.5%) in TACE-Len-Sin group.The incidence of gastrointestinal bleeding (GB) was significantly higher in the TACE-Ate-Bev group compared to the TACE-Len-Sin group (10.8% vs. 6.3%). Notably, GB was significantly more frequent in patients with portal hypertension (PHT) compared to those without, in both the TACE-Bev-Ate group (28.2% vs. 6.8%, p < 0.001) and the TACE-Len-Sin group (24.5% vs. 3.2%, p < 0.001). Conclusions: TACE-Ate-Bev demonstrated superior OS and PFS compared to TACE-Len-Sin as first-line treatment for advanced HCC, with an acceptable safety. Management of PHT in patients with advanced HCC is critical to optimizing patient outcomes.