Adjuvant donafenib plus anti–PD-1 therapy in hepatocellular carcinoma with high-risk features after curative resection: A real-world study.

Abstract

e16254 Background: Patients with hepatocellular carcinoma (HCC) and high-risk pathological features have a substantial risk of recurrence after curative resection, and effective adjuvant systemic therapies remain an unmet need. Evidence for postoperative combination therapy in real-world settings is limited. We conducted a real-world study to evaluate the efficacy and safety of adjuvant donafenib plus anti–PD-1 therapy in this population. Methods: This single-center retrospective study included HCC patients who underwent R0 resection followed by adjuvant donafenib plus anti–PD-1 therapy. Eligible patients had ECOG 0–1, Child–Pugh ≤7, and at least one high-risk feature, including tumor diameter ≥5 cm, tumor number ≥2, microvascular invasion (MVI), satellite nodules, or surgical margin <1 cm. The primary endpoint was 1-year recurrence-free survival (RFS). Secondary endpoints included overall survival (OS) and safety. Survival outcomes were estimated using the Kaplan–Meier method, and prognostic factors were explored using Cox regression. Results: Seventy-seven patients were included. Overall, 26% had BCLC stage B or C disease, and 70.2% presented with two or more high-risk features. MVI was observed in 53.2% of patients, and most MVI-positive patients had additional high-risk factors. Median follow-up was 29.35 months. Median time from surgery to initiation of adjuvant therapy was 0.99 months. At data cutoff, 28 patients experienced recurrence and 5 patients died, all after recurrence. Median RFS was not reached; the 1- and 2-year RFS rates were 79.7% and 60.9%, respectively. Among patients with recurrence, intrahepatic recurrence predominated (n=16), followed by extrahepatic recurrence (n=6) and combined intrahepatic and extrahepatic recurrence (n=5); one recurrence pattern was unknown. OS outcomes were favorable, with 1- and 2-year OS rates of 98.5% and 94.8%, respectively, and median OS not reached. In multivariate analysis, portal vein tumor thrombosis (PVTT) was an independent adverse prognostic factor for RFS (HR 4.59, 95% CI 1.53–13.78; P=0.007). MVI showed a consistent trend toward poorer RFS (HR 2.01, 95% CI 0.89–4.57; P=0.094). Patients with two or more high-risk features tended to have shorter RFS than those with one high-risk feature (HR 2.59, 95% CI 0.98–6.84; P=0.054).Treatment-related adverse events occurred in 75% of patients. Grade 3 adverse events were reported in 10%, with no grade 4 or 5 events. Conclusions: In this real-world study of resected HCC patients with substantial recurrence risk, adjuvant donafenib combined with anti–PD-1 therapy demonstrated encouraging RFS outcomes with manageable safety. Recurrence was predominantly intrahepatic, and PVTT and MVI remained key adverse prognostic factors. These findings support further prospective evaluation of this postoperative adjuvant strategy.