Adjuvant Lenvatinib in Combination with Transarterial Chemoembolization for Hepatocellular Carcinoma Patients with High-Risk of Postoperative Recurrence: A Prospective Cohort Study

Abstract Background The high probability of tumor recurrence after curative surgery hinders the survival of patients with hepatocellular carcinoma (HCC). This prospective cohort study aimed to evaluate the efficacy and safety of lenvatinib (LEN) plus transarterial chemoembolization (TACE) as an adjuvant therapy in pre-defined HCC patients with high-risk of postoperative recurrence. Methods Patients who met the eligible criteria were enrolled between November 2018 to May 2021 from 8 hepatobiliary centers in China. The primary endpoint was disease-free survival (DFS). The secondary endpoints were overall survival (OS) and safety. Additionally, propensity score matching (PSM) and other propensity score analyses were performed to balance the potential confounding factors between groups to validate the conclusion. The treatment-related adverse events (AEs) were recorded throughout the entire study period. Results A total of 297 patients were enrolled, with 147 patients in the LEN + TACE group and 150 patients in the TACE group. Before PSM, patients in the LEN + TACE group achieved significantly better DFS than those in the TACE group (19.0 vs. 10.0 months, P = 0.011). PSM analysis identified 111 matched pairs of patients. LEN + TACEgroup also showed longer DFS in than the TACE group after PSM (19.0 vs. 9.0 months, P = 0.018). Further other three propensity score analyses yielded similar DFS benefit tendency after the potential confounding factors were adjusted in two groups. Although the median OS had not been reached in either of the two groups, both primary cohort and PSM cohort showed favorable OS benefit tendency in the LEN + TACE group. Intrahepatic recurrence was the most common recurrent location in both groups. Lenvatinib treatment-related AEs of grade 3 or 4 occurred in 28.6% of the patients in LEN + TACE group. Conclusions This study suggested that adjuvantlenvatinib plus TACE might be a promising approach for HCC patients with high-risk of postoperative recurrence, which could significantly reduce postoperative recurrence and prolong survival with a manageable safety profile. Trial Registration ClinicalTrials.gov Identifier: NCT03838796.