1011P A prospective study of TACE combined with lenvatinib plus sintilimab for HCC with portal vein tumor thrombus

Portal vein tumor thrombus (PVTT) has a high incidence and poor prognosis in hepatocellular carcinoma (HCC) patients, and the treatment demand for such patients is currently unmet. This study aimed to evaluate efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib and sintilimab in HCC with PVTT. In this prospective study, eligible participants were enrolled and randomized (1:1) into TACE combined with lenvatinib and sintilimab (TACE-LEN-SIN) group and TACE combined with lenvatinib (TACE-LEN) group. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included overall survival (OS), objective response rate (ORR) and disease control rate (DCR) according to mRECIST, and safety. 116 patients were enrolled from January 2022 to December 2022, 58 patients in each group. Patients had a median age of 50 (range, 51-64.2) years and mostly were male (80.2%). Hepatitis B virus infection was the main cause of HCC (85.3%). 37 (31.9%) patients had extrahepatic metastases. As of April 2023, 49 (84.5%) patients in the TACE-LEN group had disease progression and 38 (65.5%) died, while 37 (63.8%) patients in the TACE-LEN-SIN group had disease progression and 16 (27.6%) died. Both median PFS (4.17 vs. 3.33 months, P = 0.01) and median OS (not reached (NR) vs. 8.53 months, P = 0.003) in the TACE-LEN-SIN group were significantly longer than those in the TACE-LEN group. ORR (22.4% vs. 12.1%, P = 0.219) and DCR (69.0% vs. 53.4%, P = 0.127) were slightly higher in the triple group than in the dual group. The results of multivariate Cox regression also found that TACE-LEN-SIN treatment was an independent protective factor for PFS (HR: 0.62, 95% CI: 0.40 – 0.95, P = 0.028) and OS (HR: 0.45, 95% CI: 0.25 – 0.82, P = 0.008). The most common adverse events (AEs) were hypertension, diarrhea and fatigue. And no significant differences in the incidence of AEs between the two groups, except for those related to Sintilimab. TACE combined with lenvatinib and sintilimab improved survival outcomes without increasing the unpredictable safety profile compared with TACE combined with lenvatinib for HCC with PVTT.