Donafenib combined with anti–PD-1 antibody as adjuvant therapy for patients with hepatocellular carcinoma at high risk of recurrence after resection.

e16266 Background: A growing incidence of hepatocellular carcinoma and its high risk of recurrence after curative-intent treatment underscore the need for effective adjuvant treatment options. This study aimed to assess the efficacy of adjuvant donafenib with anti-PD-1 in patients with hepatocellular carcinoma (HCC) following radical resection. Methods: This single-center retrospective study enrolled primary HCC patients with high risk recurrence factors who underwent R0 resection at Hunan Provincial People's Hospital from October 2021 to November 2024. High-risk recurrence factors included: microvascular invasion (MVI), tumor diameter ≥5 cm, the number of tumors ≥ 2, satellite lesions and poor tumor differentiation (Edmondson stage III-IV). Patients received adjuvant therapy of donafenib combined with anti-PD-1 after surgery. Patients’ demographic characteristics, etiological characteristics, 1-year recurrence-free survival rate (RFSR), recurrence-free survival (RFS), overall survival (OS), and treatment-related safety were analyzed. Results: A total of 55 patients were enrolled with a median age of 58.9 years, 89.1% were male. Patients were classified as CNLC stage Ia/Ib/IIa/IIb/IIIa 12.7%/29.1%/9.1%/14.5%/34.5%. 50 patients (90.9%) were coinfected with HBV. All patients had an ECOG PS score of 0 and Child-Pugh grade A. Preoperative serum a-fetoprotein levels were ≥400 ng/mL in 30.9%. A total of 26 patients (47.3%) with MVI were pathologically reported after surgery, classified as M1 in 10 and M2 in 16. Additionally, 35 patients (63.6%) had a tumor diameter ≥5cm, 16 patients (29.1%) had had two or more tumors, and 14 patients (25.5%) had satellite lesions. Poorly differentiated tumors (Edmondson grade III-IV) were present in 38 patients (69.1%). 36 patients (65.5%) had more than one risk factor. The median follow up duration was 7.72 months (95% CI: 6.63-9.29), 6 patients experienced recurrence. The 6-month and 1-year recurrence-free survival rate was 91.6%（95% CI：84.0%-99.8%）, and 84.8% (95% CI: 73.8%-97.4%) respectively. The median RFS and OS were not reached. Patients with two or more tumors or satellite lesions exhibited higher rate of tumor recurrence after operation. Among all the patients who received adjuvant therapy, 47(85.5%) patients had at least one treatment-related adverse events (TRAE). TRAEs ≥Grade 3 occurred in 11 (20.0%) patients. Common TRAEs included platelet count decreased (40.0%), lymphocyte count decreased (27.3%), hand-foot syndrome (25.5%), white blood cell count decreased (21.8%). Conclusions: The combination of donafenib and anti-PD-1 antibody as adjuvant therapy demonstrated promising efficacy and was well tolerated in HCC patients with high risks of recurrence.