The efficacy and safety of bevacizumab as a salvage therapy for patients with advanced hepatocellular carcinoma targeting immune tolerance

Longhao Zhang; Jingnan Xue; Nan Zhang; Yunchao Wang; Xu Yang; Shanshan Wang; Mingjian Piao; Kai Liu; Chengpei Zhu; Yanyu Wang; Jiashuo Chao; Cong Ning; Xinmu Zhang; Ziyu Xun; Yiran Li; Huishan Sun; Xiaobo Yang; Lijin Zhao; Haitao Zhao

The efficacy and safety of bevacizumab as a salvage therapy for patients with advanced hepatocellular carcinoma targeting immune tolerance

Am J Cancer Res. 2023 Aug 15;13(8):3582-3590. eCollection 2023.

Authors

Longhao Zhang^{1

2}, Jingnan Xue^{1

2}, Nan Zhang², Yunchao Wang², Xu Yang², Shanshan Wang², Mingjian Piao², Kai Liu^{1

2}, Chengpei Zhu², Yanyu Wang², Jiashuo Chao², Cong Ning², Xinmu Zhang², Ziyu Xun², Yiran Li², Huishan Sun², Xiaobo Yang², Lijin Zhao¹, Haitao Zhao²

Affiliations

¹ Digestive Disease Hospital Affiliated to Zunyi Medical University, Department of General Surgery, Affiliated Hospital of Zunyi Medical University Zunyi 563099, Guizhou, China.
² Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100730, China.

PMID: 37693157
PMCID: PMC10492105

Abstract

As is well understood that malignant tumour progression requires additional blood vessels to provide the nutrients necessary for growth. Many patients with advanced hepatocellular carcinoma (aHCC) experience disease progression after treatment with lenvatinib (Lenva) and immune checkpoint inhibitors (ICIs). Therefore, we designed a double-arm retrospective study to evaluate the antitumour activity of additional bevacizumab (Beva, an anti-vascular endothelial growth factor-targeting drug) as a means to reduce the blood vessels needed for tumour growth. Compared with the control group, the group that received Beva had prolonged progression-free survival (PFS) and a trend toward a benefit for overall survival duration. This study aimed to evaluate the anticancer effect of Beva in patients with aHCC who experienced tumour progression after treatment with Lenva+ICIs. From April 2021 to March 2023, we retrospectively included 20 patients as the experimental group and 21 patients as the control group. The patients in the experimental group experienced disease progression after receiving targeted therapy and ICIs, after which we added Beva to the treatment. The patients in the control group only received targeted therapy and ICIs. The efficacy endpoints were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR), which were evaluated according to RECIST v1.1. Adverse events were assessed using NCI-CTCAE v5.0. Ultimately, 20 patients with aHCC in the experimental group of received Beva after disease progression, compared with 21 patients in the control group. The median OS was 12.6 mo (95% CI: 6.8-18.7) vs. 9.3 mo (95% CI: 4.3-14.4), and the median PFS was 6.9 mo (95% CI: 6.4-7.4) vs. 4.1 mo (95% CI: 2.4-5.8). The ORR for all patients was 5%, and the DCR for all patients was 70.0%. The median follow-up time for all patients was 7.5 mo (95% CI: 5.0-10.0). All patients had adverse events, but no fatal adverse events were observed. In conclusion, Bevacizumab is a drug resistant treatment option for patients with advanced hepatocellular carcinoma after Lenva+PD-1/PD-L1 treatment.

Keywords: Bevacizumab; advanced hepatocellular carcinoma; immune checkpoint inhibitors; lenvatinib; targeted immunotherapy; tumor resistance.