Adjuvant donafenib for patients with hepatocellular carcinoma at high risk of recurrence following radical resection: A multi-center, retrospective study in China.

e15129 Background: The implementation of adjuvant therapy in reducing tumor recurrence of hepatocellular carcinoma (HCC) is an essential approach for extending the prognosis of patients. The exploration of treatment strategies that are both efficacious and secure remains a prominent area of research in recent years. Donafenib is a novel, oral, small-molecule, multikinase inhibitor, and has demonstrated promising efficacy and safety profiles in preclinical and clinical studies. However, there is currently a lack of reported data on the adjuvant donafenib for HCC following radical resection (R0). The present study aimed to explore the efficacy and safety of adjuvant donafenib for HCC patients at high risk of recurrence following R0. Methods: This retrospective study analyzed 196 patients who underwent R0 for HCC between April 2021 and October 2022. All patients exhibited at least one of the following high risk recurrence factors:① single lesion > 5 cm or multiple lesions of any size; ② microvascular invasion (MVI); and ③ satellite nodules. Among these patients, 49 received donafenib, while 147 (control group) did not. In the donafenib group, donafenib was administered at a dose of 100 or 200 mg bid until tumor recurrence and serious adverse events (AEs). The 1-year and 2-year recurrence-free survival (RFS) rates and overall survival (OS) rates were compared between the two groups, as well as the incidence of adverse events (AEs) in the donafenib group. Inverse probability of treatment weighting (IPTW) was used. Results: The patient population consisted of 167 males and 29 females, with a median age of 59 (range 30-83). All patients exhibited a high risk of recurrence (number of tumors single/multiple, 167/29; tumor size within 5.0/above 5.0 cm, 78/118; MVI yes/no, 140/56; satellite nodules yes/no, 39/157). The median follow-up was 21.8 (range 3.8-32.0) months. Before IPTW, the donafenib group exhibited significantly higher 1-year and 2-year RFS rates compared to the control group (83.7%, 68.0% vs 66.7%, 47,6%, p = 0.023), while no significant difference in 1-year and 2-year OS rates (97.8%, 93.9% vs 91.8%, 80.6%, p = 0.120). After IPTW, the 1-year, 2-year RFS rates and OS rates were more favorable for the donafenib group compared to the control group (86.6%, 72.5% vs 64.8%, 45.0%, P = 0.004; 97.9%, 95.6% vs 89.5%, 77.9%, P = 0.043, respectively). In the donafenib group, AEs occurred in 44 patients, including 39 with grade 1 or 2 AEs and 5 with grade 3 AEs. The most common AEs included hand-foot skin reaction, decreased platelet count, and diarrhea. Conclusions: Adjuvant donafenib may improve RFS of HCC patients at high risk of recurrence following R0, while exhibiting favorable safety. This finding deserves further exploration.