Efficacy and safety analysis of hepatic arterial infusion chemotherapy plus PD-1/PD-L1 antibodies combined with donafenib or bevacizumab in patients with unresectable hepatocellular carcinoma.

e16155 Background: In unresectable hepatocellular carcinoma (uHCC), it is unknown whether donafenib plus hepatic arterial infusion chemotherapy (HAIC) and PD-1/PD-L1 antibodies (DonaHP) shows comparable efficacy and safety to bevacizumab plus HAIC and PD-1/PD-L1 antibodies (BevHP). This study aimed to compare the efficacy and safety of DonaHP and BevHP as first-line treatments for unresectable HCC. Methods: Patients who were diagnosed with uHCC and initially treated with DonaHP or BevHP at the Sun Yat-sen University Cancer Center between April 2022 and July 2023 were retrospectively enrolled. The primary outcome was overall survival (OS), and the secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR), all of which were assessed according to RECIST v1.1, as well as safety. Propensity score matching (PSM) was performed to balance patient characteristics between the two groups. Results: In total, 175 patients (64 in the DonaHP group and 111 in the BevHP group) were included. The mean age was 54.1 years, and 163 (93.1%) patients were male. The median intrahepatic tumor size was 9.8 cm, and multiple tumors were recorded in 134 (76.6%) patients. Macrovascular invasion and extrahepatic metastases were present in 92 (52.6%) and 33 (18.9%) patients, respectively. Before PSM, The 1-, 2-, and 3-year OS rates were 85.3%, 63.1% and 57.8% in the DonaHP group versus 78.6%, 52.7% and 44.1% in the BevHP group (HR: 0.712, 95% CI: 0.448–1.132, P = 0.174). The median PFS was 15.3 months versus 10.3 months (HR: 0.595, 95% CI: 0.411–0.863, P = 0.010). According to RECIST v1.1, the ORR was 48.4% versus 49.5% (P > 0.999), and the DCR was 93.8% versus 86.5% ( P = 0.217). After PSM, 57 patients were included in each group, the 1-, 2-, and 3-year OS rates were 89.0%, 67.2% and 61.3% in the DonaHP group versus 81.8%, 47.9% and 38.5% in the BevHP group (HR: 0.532, 95% CI: 0.304–0.932; P = 0.033). The median PFS was 16.2 months versus 8.1 months (HR: 0.575, 95% CI: 0.359–0.932, P = 0.019). There was no statistically significant difference in the overall incidence of adverse events (AEs) between the DonaHP group and the BevHP group ( P = 0.366), although distinct patterns of specific AEs were observed. Twenty-one (32.8%) patients in the DonaHP group experienced grade 3/4 AEs, whereas 38 (33.8%) patients in the BevHP group experienced grade 3/4 AEs ( P = 0.848). Conclusions: Donafenib plus HAIC and PD-1/PD-L1 antibodies has potential superior anti-HCC efficacy compared with bevacizumab plus HAIC and PD-1/PD-L1 antibodies.