A retrospective study on the efficacy and safety of donafenib combined with transarterial chemoembolization (TACE) and with/without immunotherapy in intermediate-advanced hepatocellular carcinoma (HCC).

e16171 Background: Recent phase III clinical trial ZGDH3 and several real-world studies have demonstrated the potential of Donafenib in improving overall survival (OS) in advanced HCC. This study aims to evaluate the efficacy and safety of Donafenib combined with TACE and with/without immunotherapy as first-line treatment in intermediate-advanced HCC. By retrospectively analyzing data from previous clinical trials, we will further explore the potential of Donafenib in enhancing the survival rate of patients with intermediate-advanced HCC and its safety profile. Methods: Thirty-eight patients diagnosed with intermediate-advanced HCC through pathology or clinical assessment were included in the study. We conducted a retrospective analysis of the efficacy and safety of patients treated with at least one cycle of Donafenib between September 2021 and December 2023, at the Affiliated Hospital of Nantong University and the Third People's Hospital of Nantong City. The primary endpoints were Objective Response Rate (ORR) and Progression-Free Survival (PFS). Secondary endpoints included Disease Control Rate (DCR), overall survival (OS) and safety. Safety and efficacy were assessed according to CTCAE v5.0 and mRECIST, respectively. Survival data were calculated using the Kaplan-Meier method. Results: The median age was 67 years old, and 76.3% were male. 39.5% of patients had Child-Pugh score A, 39.5% had BCLC stage B, and 60.5% had stage C. 17 patients (44.7%) received Donafenib combined with TACE treatment, while the remaining patients (55.3%) received Donafenib combined with TACE and immunotherapy. The median duration of therapy (mDOT) was 7.18 months (range, 2.14 -21.75). The ORR and DCR were 57.89% (22/38) and 89.47% (34/38), respectively. The median follow-up time was 9.17 months (range, 2.99-27.93), and the 6-month PFS rate was 81.1% (95% CI: 67.1%-98.0%). The 12-month PFS rate was 73.7% (95% CI: 56.5%-96.2%). The 6-month OS rate was 94.0% (95% CI: 86.2%-100.0%), and the 12-month OS rate was 88.1% (95% CI: 75.6%-100.0%), with the median PFS and OS not reached yet. Most patients took Donafenib 200mg twice a day. A total of 6 patients (15.79%) experienced grade 3 adverse events (AEs). The common grade 3 AEs included hand-foot syndrome (7.89%), diarrhea (2.63%), rash (2.63%), and hypertension fatigue (2.63%). No grade 4 or 5 AEs or new safety signals were found. Conclusions: Donafenib combined with TACE and with/without immunotherapy showed manageable safety and promising efficacy in intermediate-advanced HCC patients.