The efficacy and safety of postoperative adjuvant donafenib therapy for patients with high-risk recurrence hepatocellular carcinoma after radical resection: A multicenter retrospective study in China.

Abstract

e16274 Background: Hepatectomy is a crucial treatment for long-term survival in patients with HCC; however, the high recurrence rate impacts prognosis. Currently, there is no standard adjuvant therapy for this patient population. This study investigates efficacy and safety of Donafenib as postoperative adjuvant therapy for patients with a high risk of recurrence after radical resection of HCC. Methods: We analyzed clinicopathological data of HCC patients with a high risk of recurrence after radical resection, recruited from 7 medical centers between January 2021 and October 2024. High risk was defined by tumor diameter > 5 cm; multiple lesions; microvascular invasion (MVI) grade 1 or 2; lesions complicated by tumor thrombus (TT); and alpha-fetoprotein (AFP)≥200 μg/L. Patients with Donafenib Group received Donafenib monotherapy (D) or combination regimens (D+TACE-DT, D+ICI-DI) as adjuvant therapy, and Control Group underwent observation. We examined recurrence-free survival (RFS), overall survival (OS), and safety according to CTCAE 5.0. Results: 394 HCC patients were included, with a median age of 59 years at the data cut-off in August 2025. The median follow-up time is 22.9 months (IQR 14.3 -32.6) in Donafenib Group and 39.1 months (IQR 24.0-45.8) in Control Group. The Donafenib Group contains 219 patients (101 D, 85 DT and 33 DI) and Control Group 175 patients. The general cohort comprised 82.0% males, 77.9% with HBV infection, 91.6% with Child-Pugh A, 86.2% with ECOG PS 0. 50.5% had multiple high-risk factors, 47.7% had tumors > 5 cm, 26.6% multiple lesions, 58.4% MVI grade 1 or 2, 7.4% TT, and 36.0% AFP≥200 μg/L. The median RFS was prolonged in Donafenib Group compared with Control Group (38.6 months vs. 20.4 months; HR, 0.592; 95% CI: 0.442–0.792; p = 0.0004). The RFS rates at 2 and 3 years were 62.0% (54.4–68.7) and 56.9% (47.8–65.0) in Donafenib Group, 46.7% (39.1–53.9) and 36.8% (29.6–44.1) in Control Group. The OS was improved in Donafenib Group (HR, 0.531; 0.324–0.870; p = 0.0108). The OS rates at 2 and 3 years were 89.0% (83.4–92.8) and 88.1% (82.1–92.2) in Donafenib Group, 79.3% (72.4–84.7) and 71.7% (64.1–77.9) in Control Group, respectively. Multivariate analysis identified MVI and China liver cancer stage IIIA as independent risk factors for RFS. Postoperative adjuvant Donafenib was an independent protective factor for RFS (HR, 0.513; p < 0.0001) and OS (HR, 0.523; p = 0.0113). 91 patients (41.6%) experienced treatment-related adverse events (TRAE) of any grade, grade 3 TRAE 4.6% concluding with rash (3.2%), hand-foot syndrome (0.9%) and thrombocytopenia (0.5%); no patients experienced grade 4 or 5 TRAE. Conclusions: Postoperative adjuvant Donafenib was associated with prolonged RFS and OS in HCC patients with high risk of recurrence following radical resection, with a manageable safety profile.