The efficacy and safety of donafenib as postoperative adjuvant therapy in patients at high risk of recurrence following radical resection of hepatocellular carcinoma (HCC): A multicenter retrospective study.

Abstract

4134 Background: Hepatectomy is a crucial treatment for long-term survival in patients with HCC; however, the high recurrence rate significantly impacts prognosis. Currently, there is no standard adjuvant therapy for this patient population. This study investigates the 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 the clinicopathological data of HCC patients with a high risk of recurrence after radical resection, recruited from six medical centers between June 2021 and October 2024. High risk was defined by the presence of any of the following criteria: [i] tumor diameter > 5 cm; [ii] multiple lesions of any size; [iii] microvascular invasion (MVI) grade 1 or 2; [iv] lesions complicated by tumor thrombus (TT); and [v] alpha-fetoprotein (AFP)≥200 μg/L. Patients received either Donafenib monotherapy (D) or combination regimens (D+TACE-DT, D+ICI-DI, or D+TACE+ICI-DTI) as adjuvant therapy. We examined the relapse-free survival (RFS), overall survival (OS), and safety according to CTCAE 5.0. Results: 199 patients were included in this study, with a median age of 60 years (IQR: 53-67) at the data cut-off in January 2025. The cohort comprised 85.7% males, 83.4% with HBV infection, 87.9% with Child-Pugh A, and 79.4% with ECOG PS 0. Among patients at high risk, 52.3% had multiple high-risk factors, 53.3% had tumors > 5 cm, 27.1% had multiple lesions, 53.3% had MVI grade 1 or 2, 13.6% had TT, and 36.7% had AFP≥200 μg/L. Treatment distribution included 70 patients receiving D therapy, 69 receiving DT therapy, 46 receiving DI therapy, and 14 receiving DTI therapy. At the data cut-off, the median RFS for the overall population was 27.8 months (95%CI:22.3 months -NE), with a one-year RFS rate of 72.9% (95%CI:66.0%-80.5%) and two-years RFS rate of 55.4% (95%CI: 45.6%-67.2%). In subpopulations based on treatment regimens (D, DT, DI, DTI), the median RFS was 24.5 months (95%CI:20.6 months -NE), 29.2 months (95%CI:22.3 months -NE), 30.0 months (95%CI:19.0 months -NE), and 20.5 months (95%CI:9.3 months -NE), respectively. The median OS for the overall population and subpopulations had not yet been achieved. Among the overall population, 114 patients (57.3%) experienced treatment-related adverse events (TRAE) of any grade, with an incidence of grade 3 TRAE at 8.0% concluding with rash (5.5%), hand-foot syndrome (2.0%) and thrombocytopenia (0.5%); no patients experienced grade 4 or 5 TRAE. Conclusions: These preliminary results showed that donafenib as postoperative adjuvant therapy may effectively reduce the recurrence rate in patients at high risk of recurrence following radical resection of HCC, demonstrating good safety and tolerability.