Efficacy and safety of donafenib combined with PD-1 inhibitors and transarterial chemoembolization (TACE) in unresectable hepatocellular carcinoma (uHCC): A retrospective study.

e16188 Background: Emerging evidence suggests that combining TACE with tyrosine kinase inhibitors (TKIs) and PD-1 inhibitors may improve outcomes in patients with uHCC. Donafenib has been approved in China as a standard first-line systemic therapy for uHCC, and preliminary data indicate that combination regimens incorporating donafenib are promising. This study aimed to evaluate the efficacy and safety of donafenib in combination with PD-1 inhibitors and TACE in patients with uHCC. Methods: This single-center, retrospective study included patients with uHCC who received donafenib plus PD-1 inhibitor and TACE at The First Affiliated Hospital of Bengbu Medical University between February 2022 and July 2025. Eligible patients had at least one measurable lesion per modified Response Evaluation Criteria in Solid Tumors (mRECIST). The primary endpoint was progression-free survival (PFS) assessed according to mRECIST. Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and treatment-related adverse events (TRAEs). Results: A total of 48 patients with uHCC were enrolled. All patients received oral donafenib in combination with intravenous PD-1 inhibitors—camrelizumab, sintilimab, or tislelizumab—administered every 3 weeks (Q3W), along with TACE performed on an as-needed basis. The median age was 59 years (range, 47–75). 98.0% patients (47/48) had chronic hepatitis B virus (HBV) infection, and 43.8% (21/48) had baseline alpha-fetoprotein (AFP) levels ≥400 ng/mL. Thirty-one patients (64.6%) received the regimen as first-line therapy, and 17 (35.4%) as second-line therapy. As of the data cutoff (December 30, 2025), the median follow-up duration was 14.2 months (16.3 months in the first-line group; 11.7 months in the second-line group). Based on the mRECIST criteria, the best ORR was 72.9% overall (80.6% in first-line; 58.8% in second-line), and the DCR was 93.8% (93.5% in first-line ; 94.1% in second-line). The CR rate was 33.3%. Notably, the median time to response of 2.2 months in the first-line group indicated rapid therapeutic onset. Median PFS and OS were not reached. The estimated 6-month PFS rates were 92.0% (first-line) and 79.9% (second-line); the corresponding 12-month OS rates were 79.0% and 74.3%. TRAEs occurred in 33 patients (68.7%), with grade 3 events reported in 3 patients (6.3%). No grade 4 or 5 TRAEs were observed. Conclusions: The combination of donafenib, PD-1 Inhibitors,and TACE demonstrated robust antitumor activity and a favorable safety profile in patients with uHCC, both in first- and second-line settings. These encouraging results warrant validation in prospective, randomized controlled trials.