Efficacy and safety of donafenib plus transarterial chemoembolization and immunotherapy for hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide and currently lacks effective treatment options. This is particularly true for advanced HCC, for which conventional therapies often lead to a poor prognosis.

Aim: To assess the safety and efficacy of transarterial chemoembolization (TACE) with donafenib and immune checkpoint inhibitors (ICIs) for unresectable HCC.

Methods: We retrospectively assessed the data of patients with HCC who underwent TACE combined with donafenib and an ICI (tislelizumab or cedilimumab). Patients received oral donafenib daily for 2 weeks before TACE, followed by tislelizumab or cedilimumab 200 mg intravenously on day 1 of a 21-day therapeutic cycle. The primary endpoints were objective response rate, disease control rate, and duration of response according to the modified RECIST criteria. The secondary endpoint was presence of treatment-related adverse events (TRAEs).

Results: The median follow-up was 7.8 months (95%CI: 5.0-11.8 months). The objective response rate was 60.0% (18/30), while the disease control rate was 93.3%. The median duration of response in confirmed responders was 6.6 months (95%CI: 1.3-12.9 months). The median progression-free survival was 11.8 months (95%CI: 8.3-15.4 months). More than half of the patients survived until the end of the study. Grade > 3 TRAEs occurred in 40% of the patients with no grade 5 TRAEs reported. The most common grade 3/4 TRAE was palmar-plantar erythrodysesthesia, a dermatologic condition characterized by painful redness and swelling of the palms and soles, with an incidence of 56.7%. No ICI-related adverse effects were observed.

Conclusion: TACE combined with donafenib and ICI is a promising and safe therapeutic regimen for unresectable HCC.