Efficacy of Lenvatinib as Subsequent Therapy After Combination Immune Checkpoint Inhibitors for Unresectable Hepatocellular Carcinoma

Background/Aim: Durvalumab plus tremelimumab (DT) therapy has demonstrated overall survival benefit in a clinical trial and is now widely used as first-line treatment for unresectable hepatocellular carcinoma (u-HCC). However, evidence supporting the efficacy of lenvatinib (LEN) as subsequent therapy after DT progression remains limited. Patients and Methods: This multicenter study enrolled patients who received LEN as first-line therapy (1st-line LEN) and those who received LEN as second-line therapy following DT treatment (2nd-line LEN following DT). The primary endpoints were disease control rate (DCR) and objective response rate (ORR), which were compared between the 1st-line LEN and 2nd-line LEN following DT. Treatment responses were assessed using mRECIST. Results: In the intention-to-treat analysis, DCR was 69.1% in the 1st-line LEN group and 69.2% in the 2nd-line LEN following DT group (p=0.95); ORR was 38.2% and 30.8%, respectively (p=0.44). No significant differences were observed between the two groups. After adjusting for age, sex, and ALBI score, treatment line was not associated with DCR; the odds ratio for 2nd-line LEN following DT versus 1st-line LEN (reference) was 0.83 (95% confidence interval=0.17-4.13, p=0.816). Conclusion: LEN following DT therapy demonstrated equivalent antitumor efficacy to first-line LEN, supporting LEN as a viable second-line option after DT progression in u-HCC.