Adjuvant anlotinib plus TACE in hepatocellular carcinoma with postoperative high-risk recurrence: a single-arm, multi-center, phase II study

Purpose: This study assessed the efficacy and safety of anlotinib plus transcatheter arterial chemoembolization (TACE) as adjuvant therapy in hepatocellular carcinoma (HCC) at high-risk recurrence after resection. Methods: This multi-center, single-arm, phase II study (ALTER-H004) enrolled patients with TACE-eligible HCC at high risk of recurrence after surgery. Three to five days after TACE, patients received 12 mg oral anlotinib once daily on days 1–14 every 3 weeks until recurrence, extrahepatic metastasis, or discontinuation was determined by investigators. Primary endpoint was disease-free survival (DFS). Results: Twenty-nine patients were enrolled between April 2020 and August 2022. Median follow-up was 34.1 (IQR, 32.0–40.9) months. Of 27 with assessable efficacy, median DFS was 40.9 (95% CI, 11.4–70.3) months, with 1-, 2-, and 3-year DFS rates of 72.1% (95% CI, 50.2%-85.6%), 63.0% (95% CI, 40.7%-78.9%), and 56.7% (95% CI, 33.6%-74.5%), respectively. Four (14.8%) patients achieved DFS of > 36 months. Median time to recurrence (TTR) was 40.9 (95% CI, 11.4–70.3) months. Median OS was 43.3 (95% CI, not estimable [NE]-NE) months; OS rate was estimated as 92.1% (95% CI, 71.9%-98.0%) at 1 year, 87.9% (95% CI, 67.0%-96.0%) at 2 years, and 83.3% (95% CI, 61.2%-93.4%) at 3 years. Five (18.5%) patients experienced ≥ grade 3 treatment-related adverse events, including hypertension (7.4%), white blood cell decreased (7.4%), ascites (3.7%), and blood bilirubin increased (3.7%). No treatment-related deaths or serious AEs occurred. Conclusion: The study demonstrated manageable safety and promising clinical benefits of adjuvant anlotinib plus TACE for high-risk recurrent HCC following resection, indicating a potential intervention for this population. Clinical trial registration: ClinicalTrials.gov NCT04213118.