Retrospective Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 14, 2020; 26(30): 4465-4478
Published online Aug 14, 2020. doi: 10.3748/wjg.v26.i30.4465
Efficacy and safety of lenvatinib for patients with advanced hepatocellular carcinoma: A retrospective, real-world study conducted in China
Dong-Xu Wang, Xu Yang, Jian-Zhen Lin, Yi Bai, Jun-Yu Long, Xiao-Bo Yang, Samuel Seery, Hai-Tao Zhao
Dong-Xu Wang, Xu Yang, Jian-Zhen Lin, Yi Bai, Jun-Yu Long, Xiao-Bo Yang, Hai-Tao Zhao, Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Samuel Seery, Department of Humanities, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Author contributions: Wang DX and Yang X collected the data and wrote the manuscript; Lin JZ, Long JY, Bai Y and Yang XB helped to collect literature and participated in discussions; Zhao HT designed the study; Seery S and Zhao HT examined and verified the study; all authors read and approved the final manuscript.
Supported by the International Science and Technology Cooperation Projects, No. 2016YFE0107100; the Capital Special Research Project for Health Development, No. 2014-2-4012; the Beijing Natural Science Foundation, No. L172055 and No. 7192158; the National Ten-thousand Talent Program, the Fundamental Research Funds for the Central Universities, No. 3332018032; and the CAMS Innovation Fund for Medical Science (CIFMS), No. 2017-I2M-4-003 and No. 2018-I2M-3-001.
Institutional review board statement: The protocol of this study was compliant with the principles of the Declaration of Helsinki and was also approved by the Institutional Review Board and Ethics Committee at Peking Union Medical College Hospital.
Informed consent statement: All patients were fully informed of the objectives of this study and provided formal consent before being fully considered.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Hai-Tao Zhao, MD, Professor, Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing, Beijing 100730, China. zhaoht@pumch.cn
Received: March 14, 2020
Peer-review started: March 14, 2020
First decision: April 12, 2020
Revised: April 25, 2020
Accepted: July 4, 2020
Article in press: July 4, 2020
Published online: August 14, 2020
Processing time: 152 Days and 20.2 Hours
ARTICLE HIGHLIGHTS
Research background

Lenvatinib has become an indispensable part of regimens for patients with advanced hepatocellular carcinoma (aHCC). Recently, several real-world studies appear to have confirmed this.

Research motivation

Ethnicity appears to, at least partially, cause etiological differences, which necessitates further real-world studies of lenvatinib across diverse populations, such as in China.

Research objectives

To develop a more comprehensive understanding of the real-world effectiveness of lenvatinib by analyzing its efficacy and safety from a variety of aspects.

Research methods

This is a retrospective and multiregional study involving patients from across China who were diagnosed with aHCC and received lenvatinib monotherapy. Data were collected from patients during lenvatinib interventions from December 2018 to December 2019. After strict eligibility criteria were applied, efficacy was assessed using the RECIST 1.1 criteria. Baseline characteristics and adverse events (AEs) were recorded throughout the entire study.

Research results

In total, 54 HCC patients treated with lenvatinib monotherapy were included for final analysis. The majority of patients in this Chinese sample were suffering from concomitant HBV-related HCC. The objective response rate was 22% with a progression-free survival (PFS) of 168 d; however, AEs occurred in 92.8% of patients. The multivariate analysis showed that the Barcelona Clinic Liver Cancer stage, portal vein tumor thrombus and Child-Pugh classifications were significant factors affecting PFS. The sensitivity and specificity were calculated for decreasing serum biomarkers including alpha-fetoprotein in order to predict tumor size reduction. Gene sequencing also provided insights into potential gene mutation signatures related to the lenvatinib effect.

Research conclusions

Our findings confirm previous evidence from the phase III REFLECT study. Further analysis suggests that baseline characteristics, changes in serum biomarkers and gene sequencing may hold the key for predicting lenvatinib responses.

Research perspectives

Randomized controlled studies and real-world studies consistently report the beneficial effect of lenvatinib, but its application in HCC patients has only recently begun. Future research should focus on screening patients to ensure that we can identify those who will benefit most from lenvatinib and how the side effects can be effectively managed.