First-line treatments for advanced hepatocellular carcinoma: a network meta-analysis and cost-effectiveness analysis in China and the United States

Abstract

Background: Various therapeutic strategies are available for the first-line treatment of patients with advanced hepatocellular carcinoma (aHCC). But which approach is the most cost-effective remains uncertain. Objectives: This study aims to evaluate the cost-effectiveness of first-line strategies in aHCC patients from the perspective of Chinese and US payers. Design: A network meta-analysis (NMA) and cost-effectiveness study. Data sources and methods: A NMA was conducted to collect all first-line strategies with aHCC from 1 October 1 2018 until 1 January 2022. The relevant randomized controlled trial literature in PubMed, Embase, and Cochrane Library for the last 3 years were searched. The abstracts of meetings of the American Society of Clinical Oncology, European Society of Medical Oncology, and American Association for Cancer Research were also reviewed. A Markov model that included three states was developed. One-way sensitivity and probabilistic sensitivity analysis were performed to investigate the uncertainty of the economic evaluation. Scenario analysis was conducted to explore the economic benefits of treatment strategies in low-income populations. Results: Base-case analysis in China included 1712 patients showed that atezolizumab combined with bevacizumab, sintilimab combined with bevacizumab, lenvatinib (LEVA), and sorafenib (SORA) added 0.46, 1.25, 0.77, and −1.08 quality-adjusted life-years (QALYs), respectively, compared with donafenib, resulting in an incremental cost-effective ratio of $85607.88, $12109.27, and $1651.47 per QALY at a willingness-to-pay (WTP) of $11101.70/QALY. In the United States, only the incremental cost-effectiveness ratios (ICERs) of SORA was higher that were lower than the WTP threshold ($69375/QALY), and LEVA was the most cost-effective strategy with the ICERs were 25022.13/QALY. Conclusion: The NMA and cost-effectiveness analysis revealed that LEVA is the favorite choice in the first-line treatment of Chinese aHCC patients and US payers’ perspective when the WTP was $11101.70/QALY in China and $69375.0/QALY in the United States. Registration: This study has been registered on the PROSPERO database with the registration number CRD42021286575.

Cost-effectiveness and prognostic model of hepatic arterial infusion chemotherapy for hepatocellular carcinoma with high tumor burden and/or Vp4 tumor thrombus compared with sorafenib: a post-hoc analysis of the FOHAIC-1 trial

“…Similarly, Sun et al . 27 conducted a network meta-analysis and cost-effectiveness study of several treatment options, including lenvatinib, which was favored as the first-line treatment choice for advanced HCC from the perspectives of Chinese and US payers. Notably, the Phase III REFLECT trial that confirmed the noninferiority of lenvatinib to sorafenib excluded HCC patients with high-risk of Vp-4 portal vein tumor thrombus 28 .…”

Atezolizumab plus bevacizumab versus lenvatinib as first-line therapy for advanced hepatocellular carcinoma: A systematic review and meta-analysis

“…Subsequently, Sun et al . conducted a network meta-analysis with a cost-effective analysis of the first-line treatments for aHCC in China and the United States [ 27 ]. Compared to donafenib, ATE/BEV and LEN added 0.46 and 0.77 quality-adjusted life-years.…”

“…In a cost-effectiveness analysis of five systemic treatments for unresectable HCC in China, donafenib was found to be the most economical option, followed by sorafenib > LEN > sintilimab plus bevacizumab > ATE/BEV [26]. Subsequently, Sun et al conducted a network meta-analysis with a cost-effective analy-sis of the first-line treatments for aHCC in China and the United States [27]. Compared to donafenib, ATE/ BEV and LEN added 0.46 and 0.77 quality-adjusted life-years.…”

Recent advances in recurrent hepatocellular carcinoma therapy

“…Sorafenib, a multitarget tyrosine kinase inhibitor (TKI) and the first approved drug for HCC patients, is most frequently used as an adjuvant therapy in resected HCC patients[ 107 ] and as a frontline systemic treatment in patients with HCC recurrence after LT. However, the current data are mainly based on observational research due to the exclusion of Randomized Protocol studies and Asia-Pacific trials of sorafenib from the registered studies for HCC[ 107 , 108 ]. Sorafenib has a few drawbacks, including poor oral bioavailability and drug toxicities, and its OS is only marginally improved by 2.8 mo[ 107 , 109 ].…”

“…However, the current data are mainly based on observational research due to the exclusion of Randomized Protocol studies and Asia-Pacific trials of sorafenib from the registered studies for HCC[ 107 , 108 ]. Sorafenib has a few drawbacks, including poor oral bioavailability and drug toxicities, and its OS is only marginally improved by 2.8 mo[ 107 , 109 ]. The impacts of sorafenib in patients with recurrent HCC who underwent an incurable liver transplant have been estimated in several retrospective studies.…”