Efficacy and safety of transcatheter arterial chemoembolization-lenvatinib sequential therapy for patients with unresectable hepatocellular carcinoma: a single-arm clinical study.

Background: Repeated transcatheter arterial chemoembolization (TACE) could cause ischemia of the tumor tissue and increases production of angiogenic factors in patients with hepatocellular carcinoma (HCC). Lenvatinib can inhibit the expression of angiogenic factors induced by ischemia after TACE and reduce angiogenesis and tumor recurrence. TACE-lenvatinib sequential therapy may improve clinical outcomes. There have been few investigations of TACE-lenvatinib sequential therapy for the treatment of unresectable HCC. We aimed to evaluate the efficacy and safety of TACE-lenvatinib sequential therapy for unresectable HCC. Methods: From May 2018 to May 2021, 53 consecutive patients who underwent TACE-lenvatinib sequential therapy were retrospectively reviewed. Of these, 30 patients who met the inclusion criteria were selected. Lenvatinib treatment started within 1 or 2 weeks after TACE at a dose of 8 or 12 mg once daily. Treatment response was assessed using dynamic magnetic resonance imaging (MRI) according to the modified response evaluation criteria in solid tumor (mRECIST). Blood tests were also performed at every response evaluation. Patients with complete response (CR) or partial response (PR) and stable disease (SD) received continuous lenvatinib therapy, and patients with progressive disease (PD) received repeated TACE. The progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were calculated. Statistical analysis was performed using the Kaplan-Meier method. Results: The median age was 58.5±9.1 years, and 16.7% (5/30) of patients were female. A total of 12 patients were categorized as Barcelona Clinic Liver Cancer (BCLC) Stage B and 18 were BCLC Stage C. The mean follow-up time was 15.7 months. The ORR was 76.7% (23/30), and the DCR was 96.7% (29/30). The median PFS was 6.1 months, and the median OS was 20.7 months. The most common lenvatinib-related AE was rash, and the most common TACE-related AE was elevated aspartate aminotransferase (AST). No treatment-related mortality was observed. Conclusions: From our findings, TACE-lenvatinib sequential therapy may prolong OS and PFS in patients with unresectable HCC, and the side effects are acceptable. The efficacy and safety of the sequential therapy should be confirmed in multiple center randomized controlled trials (RCTs) with a large sample and sufficient follow-up period.