Efficacy and safety of TACE combined with anlotinib compared with TACE alone among patients with intermediate or advanced hepatocellular carcinoma (HCC): A randomized, controlled, phase II clinical study.

Abstract

581 Background: Anlotinib hydrochloride is an oral multi targeted tyrosine kinase inhibitor, mainly targeting VEGFR1-3, FGFR 1-4 and PDGFR α/β. Transcatheter arterial chemoembolization (TACE) is the preferred choice for the treatment of intermediate or advanced HCC. Previous studies have proved that antiangiogenic drugs combined with TACE have synergistic effects. The purpose of this study was to explore the efficacy and safety of TACE combined with anlotinib in the treatment of intermediate or advanced liver cancer compared with TACE alone. Methods: This single-center, randomized controlled, phase II study involved 38 HCC patients with BCLC staging B or C and ECOG PS ≤ 1. Enrolled pts were treated with TACE plus anlotinib (12mg, qd, d1-d14, q3w) and TACE alone until disease progression or unacceptable toxicity. The primary endpoint was progression free survival (PFS), the secondary outcomes included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. Both PFS and tumor response were assessed by investigator per RECIST v1.1. Results: At the cutoff date of April 2022, 18 pts received TACE combined anlotinib and 20 pts received TACE alone. The median PFS was 11.04 months (95%CI, 7.17-14.92) in combination group and 6.87 months (95%CI, 5.58-8.16) in TACE group (HR 0.46, 95% CI 0.23 to 0.92, P=0.022). The median OS has not been reached yet. ORR was 27.8% (95%CI, 9.7%-53.5%) and 30% (95%CI, 11.9%-54.3%) and DCR was 94.4% (95%CI 72.7%-99.9%) and 100% (95%CI 83.2%-100%), respectively, with no statistical difference.The median times of TACE are 2 and 3 respectively.The treatment-related adverse events (TRAEs) of any grade occurred in 15 patients (83.3%) and 19 patients (95%). The most common TRAEs were HFSR (61.1%), hypertension (27.8%), thrombocytopenia (11.1%) in combination group and vomiting (35%), upper abdominal liver pain (35%), upper abdomen pain (30%), low fever (10%), fatigue (10%) in TACE group.Grade ≥ 3 TRAEs occurred in 2 pts (11.1%) in combination group and 1pts (5%) in TACE group. Conclusions: Anlotinib combined with TACE is a safe and effective regimen in the treatment ofpatients with intermediate or advanced-stage hepatocellular carcinoma (HCC). This study still needs longer follow-up to evaluate its efficacy more comprehensively. Clinical trial information: NCT04066543 .