Comparative efficacy and safety of systemic therapy for advanced hepatocellular carcinoma: a systematic review and network meta-analysis

Di Wu; Binyang Jia; Muyuan Jia; Haitao Zhao; Hong Zhao; Jinxue Zhou

doi:10.3389/fonc.2023.1274754

Comparative efficacy and safety of systemic therapy for advanced hepatocellular carcinoma: a systematic review and network meta-analysis

Front Oncol. 2023 Dec 6:13:1274754. doi: 10.3389/fonc.2023.1274754. eCollection 2023.

Authors

Di Wu^#¹, Binyang Jia^#², Muyuan Jia^#³, Haitao Zhao⁴, Hong Zhao⁵, Jinxue Zhou²

Affiliations

¹ Department of Otolaryngology, Head and Neck Surgery, Graduate College of Youjiang Medical University for Nationalities, Baise, Guangxi Zhuang, China.
² Department of Hepatobiliary and Pancreatic Surgery, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China.
³ Department of Neuro-Oncology, Beijing Arion Cancer Center, Beijing, China.
⁴ Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁵ Department of Hepatobiliary Surgery, National Cancer Centre/National Clinical Research Centre for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

^# Contributed equally.

Abstract

Background: In recent years, there has been rapid development in systemic therapeutic agents for advanced hepatocellular carcinoma. However, most treatment modalities lack head-to-head comparisons, and the distinctions in their efficacy and safety have yet to be elucidated. Consequently, the accurate selection of a treatment regimen poses a significant challenge for clinicians.

Methods: This study incorporated twenty-three randomized controlled trials, encompassing fifteen first-line and eight second-line treatments, and involving a total of 14,703 patients with advanced hepatocellular carcinoma. Results: In the context of first-line treatment, it was observed that the combination of a PD-1 inhibitor with bevacizumab (1/15) significantly extended overall survival in patients with advanced HCC. Furthermore, PD-1 inhibitors combined with TKIs (1/15) and PD-1 inhibitors combined with bevacizumab (2/15) exhibited enhanced efficacy in reducing the risk of progression-free survival events. In second-line therapy, the network meta-analysis revealed that all investigational agents prolonged progression-free survival in patients with advanced hepatocellular carcinoma when compared to placebo. Cabozantinib ranked first (1/7) in this regard. However, this translated into an overall survival benefit only for cabozantinib, regorafenib, ramucirumab, and pembrolizumab, with regorafenib achieving the highest ranking (1/7).

Conclusion: In the treatment of advanced HCC, the immune checkpoint inhibitor combined with bevacizumab regimen and the immune checkpoint inhibitor combined with TKI regimen stand out as the two most effective first-line treatment options. It is noteworthy that, for patients with absolute contraindications to VEGF inhibitors, dual immunotherapy is the preferred choice. For second-line treatment, regorafenib and cabozantinib are identified as the two most effective options.

Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023440173.

Keywords: first-line treatment; hepatocellular carcinoma; immune checkpoint inhibitors; second-line treatment; targeted therapy; tyrosine kinase inhibitors.

Publication types

Systematic Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was sponsored by the Henan Provincial Medical Science and Technology Research Project (LLRGJ20220191), the Key Scientific Research Project of Colleges and Universities in He-nan Province (23A320033), the Henan Provincial Science and Technology Project (232102311080).