A retrospective study of donafenib with or without TACE as postoperative adjuvant therapy for hepatocellular carcinoma (HCC) patients at high risk of recurrence after radical resection.

Abstract

e16258 Background: Although hepatectomy offers a potential cure for HCC, postoperative recurrence remains high and adversely impacts long-term survival. Currently, no standard adjuvant therapy has been established for patients at high risk of recurrence. This study evaluated the efficacy and safety of adjuvant donafenib with or without transarterial chemoembolization (TACE) in this population. Methods: We retrospectively analyzed clinicopathological data from HCC patients with high recurrence risk after radical resection at Nantong Third People’s Hospital, between March 2023 and November 2025. High risk was defined as meeting at least two of the following criteria: tumor diameter > 5 cm; multiple tumors; microvascular invasion (MVI) positive; Edmondson–Steiner grade Ⅲ–Ⅳ; postoperative alpha-fetoprotein (AFP) at the first month ≥10 μg/L; or postoperative des-gamma-carboxy prothrombin (DCP) at the first month > 32 mAU/mL. Patients received adjuvant donafenib alone or combined with one session of TACE; the TACE procedure was performed within the first postoperative month. Recurrence-free survival (RFS), overall survival (OS), and safety (assessed per CTCAE v5.0) were analyzed. Results: At data cutoff (December 2025), 37 patients were included with a median age of 64.4 years (SD: 9.0), most were male (73.0%), and had HBV infection (89.2%). All patients with Child-Pugh A liver function and ECOG PS 0. High-risk features included: tumor > 5 cm (29.7%), multiple lesions (37.8%), MVI-positive (73.0%), Edmondson-Steiner grade Ⅲ (89.2%), postoperative AFP≥10 μg/L (18.9%), and postoperative DCP > 32 mAU/mL (32.4%). Treatment distribution included donafenib monotherapy (n = 19) and donafenib plus TACE (n = 18). For the overall population, median RFS and OS were not reached, and the 1-year RFS rate was 76.4% (95% CI: 59.8–97.8%); the 2-year RFS rate was 67.9% (95% CI: 48.5–95.2%). Subgroup analyses were performed based on treatment, biomarker levels, and pathological features. The 1-year RFS was 81.2% for donafenib alone and 73.3% for donafenib plus TACE. According to postoperative AFP levels, the 1-year RFS was 57.1% in patients with AFP≥10 μg/L and 81.3% in those with AFP < 10 μg/L. By MVI status, the rate was 100.0% in MVI-negative patients and 71.1% in MVI-positive patients. According to Edmondson–Steiner grade, the 1-year RFS was 100.0% for grade Ⅱ and 74.9% for grade Ⅲ. Treatment-related adverse events (TRAEs) occurred in 7 patients (18.9%), all grade 1–2; no grade ≥3 TRAEs were observed. Conclusions: In this retrospective analysis, adjuvant donafenib with or without TACE demonstrated promising recurrence-free survival with a favorable safety profile in HCC patients at high risk of recurrence after radical resection. These results support further investigation in prospective studies.