Efficacy and safety of donafenib combined with TACE and with/without PD-(L)1 inhibitors for unresectable hepatocellular carcinoma (uHCC): A multicenter retrospective study.

e16212 Background: Donafenib(Dona) have shown superiority over sorafenib in improving OS and has favorable safety and tolerability in Chinese patients with advanced HCC. Transarterial chemoembolization (TACE) can effectively reduce tumor burden by delivering chemotherapy drugs directly to the tumor while blocking its blood supply. This study aims to assess the clinical efficacy of combination therapy (Dona+TACE±PD-(L)1 ) in uHCC and monitor changes in liver function throughout the treatment course. Methods: In this retrospective study, we collected patients diagnosed with uHCC who received a combination therapy of Dona plus TACE with/without PD-(L)1 inhibitors Dona＋TACE±PD-(L)1 as the first-line therapy at The First Affiliated Hospital of Sun Yat-sen University, The First Affiliated Hospital of Guangxi Medical University, The Third Affiliated Hospital of Sun Yat-sen University, The First People's Hospital of Foshan and The Affiliated Cancer Hospital and Institute of Guangzhou Medical University from January 2022 to July 2025. The primary endpoint was progression-free survival (PFS) according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST), secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. Results: A total of 142 patients were enrolled (53 in Dona＋TACE group, 89 in Dona＋TACE ＋PD-(L)1 group ). Among all patients, median age was 59 years, 129 patients (90.8%) were male, 79(56.0%) were at BCLC stage C. Most of the disease etiology was HBV (82.4%), 103 (72.5%) had cirrhosis. Most patients had multiple lesions (75.4%), hepatic venous invasion was observed in 63 (44.4%) of the patients, median maximum tumor diameter was 7.3cm (IQR, 4.9-10.3). Most patients had good liver function reserve (Child-pugh A, 78.2%; ALBI grade1, 25.7%; ALBI grade2, 67.1%). The median number of TACE sessions per patients was 2 (IQR, 1-4). Up to the date of January 12,2026, the median follow-up was 22.8 months. The median PFS was 11.6 months (95%CI: 8.8-14.4), and the PFS rates at 6months and 12 months were 72.0% and 48.5%, respectively, the OS rates at 1 year and 2 years were 80.3% and 63.8%, respectively. Based on the mRECIST criteria, the best ORR and DCR were 69.7% (n = 99) and 95.1% (n = 135), respectively. For Dona＋TACE group and Dona＋TACE ＋PD-(L)1 group, the ORR was 67.9% and 71.0%, respectively. Among the 113 evaluable patients, 89 patients (78.8%) maintained or improved ALBI grading at the end of treatment. 41.5% of patients experienced any grade treatment-emergent adverse events (TEAEs), while only 12.7% of patients experience grade 3 or 4 TEAEs, and no treatment-related deaths occurred. Conclusions: Donafenib plus TACE and with/without PD-(L)1 inhibitors showed encouraging antitumor activity and manageable safety, which maybe a potential regimen option for uHCC.