Comparison of Efficacy of Systemic Therapies in Advanced Hepatocellular Carcinoma: Updated Systematic Review and Frequentist Network Meta-Analysis of Randomized Controlled Trials

Robin Park; Laercio Lopes da Silva; Voravech Nissaisorakarn; Ivy Riano; Stephen Williamson; Weijing Sun; Anwaar Saeed

doi:10.2147/JHC.S268305

Comparison of Efficacy of Systemic Therapies in Advanced Hepatocellular Carcinoma: Updated Systematic Review and Frequentist Network Meta-Analysis of Randomized Controlled Trials

J Hepatocell Carcinoma. 2021 Mar 22:8:145-154. doi: 10.2147/JHC.S268305. eCollection 2021.

Authors

Robin Park¹, Laercio Lopes da Silva¹, Voravech Nissaisorakarn¹, Ivy Riano¹, Stephen Williamson², Weijing Sun², Anwaar Saeed²

Affiliations

¹ Department of Medicine, MetroWest Medical Center/Tufts University School of Medicine, Framingham, MA, USA.
² Department of Medicine, Division of Medical Oncology, Kansas University Cancer Center, Kansas City, KS, USA.

Abstract

Background: Several systemic agents have been approved for use in advanced hepatocellular carcinoma (aHCC). However, it is unclear which treatment is superior in either the first- or second-line settings due to the paucity of head-to-head comparative trials. Therefore, we have conducted a systematic review and network meta-analysis for the indirect comparison of the systemic agents in the first line and second line settings.

Methods: Randomized clinical trials evaluating systemic agents in first and second line settings in aHCC from inception to April 2020 were identified by searching PubMed, EMBASE, and Cochrane Databases and the annual ASCO and ESMO conferences from 2017 to 2020. Studies in English reporting clinical outcomes including overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were included. The primary outcomes of interest were pooled hazard ratios (HR) of OS and pooled odds ratios (OR) of ORR in first line studies and pooled HR of PFS and OR of ORR for second line studies. Additionally, OS for second line agents were reported in the qualitative analysis.

Results: Overall, first line studies comprised 8335 patients (13 studies) and second line studies comprised 4612 patients (11 studies). In the first line setting, atezolizumab plus bevacizumab was associated with the highest OS benefit over sorafenib (HR 0.58, 95% CI, 0.42-0.80; P-score 0.993). Additionally, lenvatinib was associated with the greatest ORR benefit (OR 3.34, 95% CI, 2.17-5.14; P-score 0.080) in the first line setting. In the second line setting, cabozantinib was associated with the highest PFS benefit over placebo (HR 0.44, 95% CI, 0.29-0.66; P-score 0.854) as well as the highest ORR benefit (OR 9.40, 95% CI, 1.25-70.83, P-score, 0.266).

Conclusion: Atezolizumab plus bevacizumab appears to have superior efficacy among first line agents whereas cabozantinib appears to be superior in the second line setting. Further studies are warranted to determine whether the type of prior therapy received affects the efficacy of subsequent second line therapy.

Keywords: advanced hepatocellular carcinoma; immunotherapy; systemic therapy; targeted therapy.

Publication types

Review

Grants and funding

The authors did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors for this research.