Efficacy and safety of transarterial therapy combined with donafenib plus programmed cell death protein-1 inhibitors for unresectable hepatocellular carcinoma.

e16210 Background: Hepatocellular carcinoma (HCC) stands as a predominant form of liver cancer, characterized by its aggressive nature and poor prognosis. Current treatment modalities, including systemic therapies, often yield suboptimal outcomes; therefore, the exploration of novel therapeutic strategies is warranted. Donafenib, a relatively new pharmacological agent, has garnered attention for its potential in enhancing the efficacy of established treatments such as programmed cell death protein-1 (PD-1) inhibitors and hepatic arterial intervention (HAIC). This study aimed to evaluate the efficacy and safety of donafenib as a first-line therapy in patients with HCC. Methods: A retrospective analysis was conducted involving 145 patients diagnosed with HCC, who underwent treatment with donafenib in conjunction with PD-1 inhibitors and either transarterial therapy (TACE or HAIC) from 2022 to 2024 at the Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi Medical University. Following strict inclusion criteria, 40 cases were excluded, primarily due to insufficient imaging or lack of efficacy assessment. Efficacy was evaluated using objective response rates based on RECIST1.1 and mRECIST criteria, while safety data focused on the incidence of grade 3-4 adverse events. Results: 105 patients were enrolled, with the media age of 53, 94 (89.5%) of 105 participants were male. The tumor stage of BCLC A/B/C were 22.9%/20%/57.1%, respectively. The objective response rates within the treated cohort were recorded at 61% and 64% according to RECIST1.1 and mRECIST criteria, with the same complete response rate of 18.1%.. The median follow-up duration was 14.2 months, revealing a median progression-free survival (mPFS) of 11.7 months, with the median overall survival (mOS) yet to be established, and 1 year OS rate was 89.9%. Notably, the study recorded an overall incidence of grade 3-4 adverse events at 77.1%, with liver enzyme elevations (ALT at 32.4% and AST at 43.8%) and lymphocyte count reductions (53.3%) dominating the safety profile. Conclusions: The preliminary findings of this single-center real-world study suggest that donafenib exhibits commendable efficacy and an acceptable safety profile as a new targeted agent in the management of hepatocellular carcinoma. Future investigations should aim to further elucidate its role in combination therapies and establish comprehensive protocols to optimize treatment outcomes for patients with HCC.