Molecular targeted therapy and immunotherapy in advanced hepatocellular carcinoma: a systematic review and Bayesian network meta-analysis based on randomized controlled trials

Abstract

Objective

The aim of this study was to compare and rank different targeted therapies or immunotherapies for advanced hepatocellular carcinoma based on efficacy.

Methods

A systematic search of the PubMed, EMBASE, and Cochrane Library databases was conducted. All systematic treatment regimens that reported comparisons with sorafenib were included in this analysis. The primary outcome measures were overall survival (OS) and progression-free survival (PFS), and other outcome measures included the objective response rate (ORR) and safety analysis according to reported treatment-related adverse events.

Results

A total of 29 RCTs involving 13376 patients were included in the analysis, including 10 single-agent therapies and 17 combination therapies. Compared with sorafenib, sintilimab plus IBI305 (HR: 0.57, 95% CI: 0.43-0.75), camrelizumab plus rivoceranib (HR: 0.62, 95% CI: 0.49-0.78), and atezolizumab plus bevacizumab (HR: 0.66, 95% CI: 0.52-0.83) ranked in the top three in terms of OS.

Conclusions

PD-1/PD-L1 inhibitors combined with anti-vascular endothelial growth factor (anti-VEGF)-targeting drugs have shown better therapeutic effects in the systematic treatment of patients with advanced hepatocellular carcinoma, and the combination of targeted and immune therapy modes should be further developed.

Keywords:

• Molecular targeted therapy
• immunotherapy
• hepatocellular carcinoma
• meta-analysis
• Bayesian

Ethical approval

Ethical approval was not needed, as this study did not require the use of patient identifiers.

Author contribution

G-Z. Wang and Y-L. Zhang participated in the conception and design of this study; Y-L. Zhang, X-J. Cui and H. Xing collected and analyzed the data; H-F. Ning and G-Z. Wang contributed to interpretation of data; Y-L. Zhang contributed to drafting of the paper; P. Dong and G-Z. Wang revised it critically for intellectual content. All authors agreed to be accountable for all aspects of the work.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The original contributions presented in the study are included in the article. Further inquiries can be directed to the corresponding authors.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This study was supported in part by grants from the Medical and Health Science and Technology Development Project of Shandong Province (No. 2019WS596), and the Natural Science Foundation of Shandong Province (No. ZR2020MH293).