Evidence of Anlotinib as First- or Second-line Monotherapy for Advanced Hepatocellular Carcinoma and Clinical Role of α-fetoprotein: a Multicenter Retrospective Study in China

Background Anlotinib, a novel multi-targeting tyrosine kinase inhibitor (TKI), has been investigated in a variety of malignant tumors. This retrospective study was designed to investigate the efficacy and safety of anlotinib as first- or second-line therapy for advanced or metastatic hepatocellular carcinoma (HCC), and to identify early predictors for disease control. Methods This multicenter retrospective study included 158 patients with advanced HCC. 54 patients received anlotinib and 104 patients received sorafenib. Progression-free survival (PFS), overall survival (OS), and treatment response were compared. Subgroup analyses and biomarker evaluations were also conducted. Results The anlotinib group demonstrated significantly longer OS (16.0 months) compared to sorafenib (14.0 months; HR: 1.779; P  = 0.002), while PFS was similar (5.0 vs. 4.0 months; HR: 1.217; P  = 0.251). Drug-related adverse effects were comparable between groups, with no new safety concerns. Subgroup analyses revealed significant benefits of anlotinib in patients with baseline AFP ≥ 400 ng/mL and in HBV-positive individuals. As for anlotinib group, AFP reduction of ≥ 25% at 4 weeks post-treatment was an independent predictor of disease control ( P  = 0.001). Conclusion Anlotinib showed promising efficacy and tolerability in Chinese patients. AFP response was an early predictor of disease control in patients with anlotinib treatment.