Efficacy and safety of donafenib combined with PD-(L)1 inhibitors plus TACE for unresectable hepatocellular carcinoma patients.

e16178 Background: Previous research suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients in realworld practice. However, the therapeutic response is associated with a decline in liver function and medicine safety, thus, the purpose of this study was to assess the clinical efffcacy of triple therapy (Donafenib + PD-(L)1 + TACE) in uHCC and monitor changes in liver function during the treatment process. Methods: This is a single center retrospective study that collected patient data from July 2022 to October 2024 who received a combination therapy of donafenib with PD-(L)1 blockades plus TACE at the interventional department of the affiliated hospital of qingdao University. Inclusion criteria were: (1) 18-75 years old; (2) At least one measurable lesion. Exclusion criteria were: (1) Previously received systemic treatment; 2) History of other cancers; 3) Incomplete clinical or follow-up information. The primary endpoint was ORR evaluated by mRECIST criteria, while secondary outcomes included PFS, OS, and safety. Results: There were 40 patients screened and included in this study, among them, 31patients (77.5%) was male，and the mean age was 65 years. Most of the disease etiology was HBV（72.5%）。At the start of treatment，most patients had good liver function reserve（Child-pugh A, 70%; ALBI grade 1, 22.5%, ALBI grade 2, 62.5%），Most patients had cirrhosis (75%). 19 patients were classified as CNLC- III. In terms of tumor characteristics, half of the patients had multiple lesions, 45% of patients have vascular invasion. Cumulative targeted lesions were 87 mm. The median PFS was 12.5 months (95% CI: 9.66 – NA), and the the PFS rates at 6 months, 12 months, and 18 months were 78.6%, 51.9%, and 32.4%, respectively. The median OS was NA (95% CI: 14– NA), and the OS rates at 12 months and 18 months were 91.7% and 66.8%, respectively. Based on the mRECIST criteria, the best ORR and DCR were 65.0% (n = 26) and 97.5% (n = 39), respectively. Among the 40 evaluable patients, 35 patients (87.5%) maintained or improved ALBI grading at the end of treatment. The change of ALBI score from baseline to the end of treatment were −2.08 to −2.14 ( p = 0.62). 62.5% of patients experienced any grade TEAEs, while only 7.5% of patients experience grade 3 TEAEs. Conclusions: Donafenib with PD-(L)1 inhibitors plus TACE showed a high tumor response rate (65%) with liver function being maintained during the treatment course.