Interim analysis of efficacy and safety of adjuvant donafenib plus transarterial chemoembolization in patients with hepatocellular carcinoma and high-risk features after curative resection.

Abstract

e16251 Background: Postoperative recurrence remains a major challenge in hepatocellular carcinoma (HCC), particularly among patients with high-risk pathological features. Currently, no globally accepted standard adjuvant therapy exists after curative resection. This study reports an interim analysis evaluating the efficacy and safety of adjuvant donafenib combined with transarterial chemoembolization (TACE) in patients with high-risk HCC following surgery. Methods: This prospective, single-arm, single-center study enrolled patients with hepatocellular carcinoma who underwent curative resection and had predefined high-risk recurrence features, including tumor size > 5 cm, microvascular invasion, satellite lesions, or portal vein tumor thrombus. Patients received donafenib (200 mg BID) combined with a fixed single session of postoperative transarterial chemoembolization for a planned duration of 6 months. The primary endpoint was 12-month recurrence-free survival rate, with secondary endpoints including recurrence-free survival, overall survival, time to recurrence, and safety. This study was registered at ClinicalTrials.gov (NCT05161143). Results: As of December 10, 2025, 25 patients were enrolled, with a median follow-up of 9.7 months. High-risk features included tumor size ≥5 cm (56.0%), MVI (56.0%), satellite lesions (20.0%), and multiple concurrent high-risk factors (36.0%), and notably, the inclusion of patients with concomitant PVTT (n = 2). At data cut-off, 4 patients experienced recurrence, including one death. The 6-month RFS rate was 95.2% (95% CI, 86.6-100), and the estimated 12-month RFS rate was 74.9% (95% CI, 56.0-100); median RFS was not reached. In subgroup analyses, 12-month RFS rates were 81.5% and 66.7% in patients with tumor size ≥5 cm and < 5 cm, respectively. Patients without MVI showed a numerically higher 12-month rate than those with MVI (80.8% vs 66.7%). No stable subgroup-specific differences were observed according to satellite lesions or PVTT. Overall survival data remain immature. Treatment-emergent adverse events (TEAEs) occurred in 84.0% of patients, with grade ≥3 TEAEs reported in 36.0%. No grade 4 or 5 treatment-related adverse events were observed. ALBI scores remained stable during treatment, with no significant difference between baseline and end of treatment (median −3.12 vs −3.14, p = 0.68), indicating preserved liver function. Conclusions: This interim analysis suggests that adjuvant donafenib combined with a single session of postoperative TACE demonstrates encouraging antitumor activity and a manageable safety profile in patients with high-risk HCC after curative resection. Longer follow-up and larger studies are warranted to confirm the durability of benefit. Clinical trial information: NCT05161143 .