Efficacy and safety of lenvatinib for patients with advanced hepatocellular carcinoma: A retrospective, real-world study conducted in China

Abstract

Background: Lenvatinib has become an indispensable part of treatment regimens for patients with advanced hepatocellular carcinoma (aHCC). Several recent real-world studies appear to have confirmed this; however, there are etiological differences. This necessitates further real-world studies of lenvatinib across diverse populations, such as in China.

Aim: To investigate the efficacy and safety of lenvatinib in a Chinese HCC patient population under real-world conditions.

Methods: This is a retrospective and multiregional study involving patients with aHCC receiving lenvatinib monotherapy. Efficacy was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1. Baseline characteristics and adverse events (AEs) were recorded throughout the entire study.

Results: In total, 54 HCC patients treated with lenvatinib monotherapy were included for final analysis. The objective response rate was 22% (n = 12) with a progression-free survival (PFS) of 168 d; however, AEs occurred in 92.8% of patients. Multivariate analysis showed that the Barcelona Clinic Liver Cancer stage [hazard ratio (HR) 0.465; 95%CI: 0.23-0.93; P = 0.031], portal vein tumor thrombus (HR 0.38; 95%CI: 0.15-0.94; P = 0.037) and Child-Pugh classifications (HR 0.468; 95%CI: 0.22-0.97; P = 0.042) were significant factors affecting PFS. The sensitivity (56.7%) and specificity (83.3%) of decreasing serum biomarkers including alpha-fetoprotein were calculated in order to predict tumor size reduction. Gene sequencing also provided insights into potential gene mutation signatures related to the effect of lenvatinib.

Conclusion: Our findings confirm previous evidence from the phase III REFLECT study. The majority of patients in this Chinese sample were suffering from concomitant hepatitis B virus-related HCC. However, further analysis suggested that baseline characteristics, changes in serum biomarkers and gene sequencing may hold the key for predicting lenvatinib responses. Further large-scale prospective studies that incorporate more basic medical science measures should be conducted.

Keywords: Efficacy; Hepatocellular carcinoma; Lenvatinib; Real-world study; Safety; Treatment.

Conflict of interest statement

Conflict-of-interest statement: The authors declare that they have no competing interests.

©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.

Figures

Figure 1

Flow diagram of study population. HCC: Hepatocellular carcinoma; ORR: Objective response rate; DCR: Disease control rate; PFS: Progression-free survival; RECIST 1.1: Response Evaluation Criteria in Solid Tumors version 1.1.

Figure 2

Progression-free survival of hepatocellular carcinoma patients treated with lenvatinib. The median progression-free survival was estimated to be 168 d (95%CI: 130–205 d).

Figure 3

Lenvatinib-related adverse events in patients with hepatocellular carcinoma. The brown bar represents grade 3-4 adverse events; the blue bar represents all-grade adverse events.

Figure 4

Progression-free survival of patients in different subgroups. BCLC: Barcelona Clinic Liver Cancer; HBV: Hepatitis B virus; PVT: Portal vein thrombus.

Figure 5

Progression-free survival of patients in different subgroups. PS: Performance Status; EHS: Extrahepatic spread.

Figure 6

Signature of gene differences based on different tumor size changes. Response standard and partial response were clustered as a group encountering tumor size reduction in response to treatment, which appears green. Tumor size change, progression standard and progressive disease were clustered into a group that did not respond with tumor size reduction, which appears red. The blue block highlights the existence of specific genes, and the left brown block represents the gene that mainly appears in either the tumor reduction or without reduction groups. SS: Response standard; ST: Tumor size change; SP: Progression standard; PD: Progressive disease; PR: Partial response.