Postoperative adjuvant donafenib-based therapy for patients with hepatocellular carcinoma at high risk of recurrence.

e16256 Background: The 5-year recurrence rate after radical resection for hepatocellular carcinoma (HCC) is as high as 70%, with early recurrence within 2 years portending a poor prognosis for high-risk patients. Given the lack of a globally standardized adjuvant therapy, this study aimed to evaluate the efficacy and safety of donafenib as postoperative treatment in this patient population. Methods: This retrospective study included patients with HCC and high-risk recurrence factors who underwent surgical resection at Beijing Ditan Hospital, Capital Medical University, between December 2023 and October 2025. High-risk recurrence factor was defined as the presence of one or more of the following: (a) multiple tumors; (b) tumor diameter > 5 cm; (c) satellite nodules; (d) microvascular invasion (MVI); (e) Edmondson-Steiner grade III–IV; or (f) a pathological margin < 1 cm. Following surgery, patients received adjuvant therapy with donafenib. Primary outcomes were recurrence-free survival (RFS), secondary outcomes included the 1-year RFS rate, overall survival (OS) and safety. Results: A total of 37 patients were included in this study. Among them, 54.1% had a tumor diameter > 5 cm, 27.0% presented with multiple tumors, and 59.5% were classified as Edmondson-Steiner grade III–IV, 45.9% of patients exhibited MVI (M1 or M2). Overall, 27 patients carried two or more high-risk factors. 24 patients received donafenib monotherapy, while 13 were treated with donafenib-based combination therapy (combined with TACE and/or PD-1 inhibitors). At a median follow-up of 12.2 months, 4 patients experienced recurrence, and all recurrences were intrahepatic. The median RFS has not yet been reached, with a 1-year RFS rate of 86.4% (95% CI 74.6% - 100.0%). The 1-year OS rate was 96.6% (95% CI 90.1% - 100.0%). While patients with a single high-risk factor had a 1-year RFS rate of 100.0%, those with ≥2 factors had a rate of 82.3%, Notably, all four recurrent patients had ≥2 high-risk factors. Among 27 patients with ≥2 high-risk factors, 19 received donafenib monotherapy and 8 received combination therapy. The 6- and 12-month RFS rates were 81.9% and 81.9%, respectively, in the monotherapy group, compared with 100.0% and 85.7% in the combination therapy group. No significant change from baseline in albumin-bilirubin (ALBI) score was observed after any treatment cycle (all P > 0.05). The scores remained stable at -2.7 ± 0.5 (baseline), -3.0 ± 1.2 (cycle 1, P = 0.41), -2.8 ± 0.4 (cycle 2, P = 0.47) and -2.8 ± 0.3 (cycle 3, P = 0.25). Treatment-emergent adverse events (TEAEs) occurred in 87.0% of patients, with Grade 3 AEs in 27.0% (n = 10). No Grade 4 or 5 AEs were observed. The most common AEs were increased ALT, anemia, and thrombocytopenia. Conclusions: In summary, adjuvant donafenib shows promise for reducing recurrence with an acceptable safety profile in high-risk HCC patients after radical resection.