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Drug-Related Hypertension Associated with the Efficacy of Apatinib on Hepatocellular Carcinoma

Authors Yang X, Hou Z, Zhu K, Zhang S, Gu X, Wang Z, Mu H, Zhou H, Chen P, Zhu X, Cui Y, Li Q, Li H, Zhang T

Received 29 November 2019

Accepted for publication 9 April 2020

Published 6 May 2020 Volume 2020:12 Pages 3163—3173

DOI https://doi.org/10.2147/CMAR.S240394

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Professor Rudolph Navari


XueJiao Yang, ZhenYu Hou, KeYun Zhu, Su Zhang, XiaoYing Gu, ZhiWei Wang, Han Mu, HongYuan Zhou, Ping Chen, XiaoLin Zhu, YunLong Cui, Qiang Li, HuiKai Li, Ti Zhang

Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, People’s Republic of China

Correspondence: Ti Zhang; HuiKai Li
Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, 24 Bin Shui Road, Hexi District, Tianjin 300060, China
Tel/Fax +86-22-2335-9984
Email zhangti@tjmuch.com; tjchlhk@126.com

Purpose: We retrospectively evaluated the efficacy and safety of apatinib as a first-line treatment for advanced hepatocellular carcinoma (HCC) and explored whether drug-related hypertension (HTN) could predict its efficacy.
Patients and Methods: This retrospective analysis included patients with advanced HCC who received oral treatment with apatinib. We evaluated the effectiveness by overall survival (OS), progression-free survival (PFS), time to progression (TTP), and disease control rate (DCR), and assessed the safety of the drug based on the occurrence of adverse events. In order to explore whether apatinib-related HTN can be used as a predictor of therapeutic effect, patients were divided into an HTN group and a non-HTN group and adjusted for propensity score-matched (PSM) to reduce mixed deviation. Subgroup analyses of negative prognostic factors for advanced HCC were also performed, including alpha-fetoprotein (AFP), Child–Pugh Score, macrovascular invasion, and extrahepatic metastasis.
Results: A total of 208 patients were analyzed, of which 40.9% (n =85) developed drug-related HTN. For all patients, the OS was 13.4 months (95% CI, 12.2– 14.6), the PFS was 5.7 months (95% CI, 5.1– 6.3), and the TTP was 6.9 months (95% CI, 6.0– 7.8). The OS of the HTN group and the non-HTN group was 17.4 months (m) and 12.5m (p=0.001), and the PFS was 7.4m and 4.7m (p=0.000), respectively. After PSM, the OS (p=0.001) and PFS (p=0.003) of the HTN group were still significantly better than the non-HTN group. Subgroup analysis suggested that overall survival was significantly longer in patients with HTN when serum AFP ≤ 400 μg/L or extrahepatic metastases. Moreover, OS in the HTN group increased significantly with or without macrovascular invasion. In addition, through the analysis of two groups of patients with PFS> 6m and PFS≤ 6m, we know that the patients with drug-related HTN may develop resistance later, so they have longer survival time.
Conclusion: Apatinib demonstrates compelling anti-cancer activity and acceptable safety in advanced HCC. Apatinib-related HTN can potentially predict prolonged survival in patients with advanced HCC.

Keywords: VEGFR-2, HTN, HCC, resistance, liver cancer

Corrigendum for this paper has been published

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