Comparison of Immunotherapy in different time in combination with Lenvatinib for the treatment of unresectable hepatocellular carcinoma: a real-world study

Abstract

Abstract Introduction: The Lenvatinib combined with immunotherapy therapies are still controversial in unresectable hepatocellular carcinoma (uHCC). This research aimed to compare the efficacy and safety of Lenvatinib monotherapy (L) and combination therapy with Lenvatinib plus immune checkpoint inhibitors (ICIs) administered synchronously (LI) and sequential therapy with initial Lenvatinib monotherapy followed by subsequent addition of ICIs (L-LI) in uHCC patients. Methods 181 uHCC patients were enrolled in this study. Patients were classified into three groups: (1) Lenvatinib monotherapy (L). (2) Synchronous administration of Lenvatinib and ICIs (LI). (3) Sequential therapy where patients initially received Lenvatinib monotherapy for 3 months followed by addition of ICIs sequentially (L-LI). Overall survival (OS) and progression-free survival (PFS), baseline characteristics, safety were compared among these groups. Results There were 108 patients in these groups after propensity score matching (PSM). OS and PFS were compared among these groups. The subgroup of patients with or without distant metastases were also compared. ECOG PS and AFP were independent prognostic factors for survival. The frequency of grade ≥ 3 AEs demonstrated no significant difference. Conclusions Our study demonstrated that, in all patients, the combination groups (LI, L-LI) had longer OS and PFS than the L group, and there was no statistical difference between the LI group and the L-LI group. However, in the subgroup of patients without distant metastases, the L-LI group exhibited longer PFS compared to the LI group. Conversely, in the subgroup of patients with distant metastases, the LI group showed longer PFS than the L-LI group.