Cost-Effectiveness of Lenvatinib in the Treatment of Patients With Unresectable Hepatocellular Carcinomas in Japan: An Analysis Using Data From Japanese Patients in the REFLECT Trial

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality in Japan. Prognosis is poor, and until recently sorafenib was the only treatment option available for patients with unresectable disease. Lenvatinib is the first therapy to demonstrate noninferiority to sorafenib. An analysis was conducted using clinical data from Japanese patients in the phase III REFLECT trial to assess the cost-effectiveness of lenvatinib versus sorafenib for first-line treatment of unresectable HCC in Japan.Methods: A partitioned survival model was implemented adopting the perspective of the Japanese healthcare system, with costs and outcomes modeled over a lifetime horizon and using a discount rate of 2%, as per Japanese guidelines. Population data from the Japanese subpopulation of REFLECT were used to extrapolate outcomes, and costs and resource use were based on Japanese sources. The Japanese tariff was applied to EQ-5D data collected during the REFLECT clinical trial to obtain utility values reflecting the preferences of the Japanese population.Results: Compared with sorafenib, lenvatinib is dominant because it is associated with a reduction in incremental costs of U156 799 and incremental quality-adjusted life-years of 0.31. These results were robust to changes in key assumptions, and probabilistic outcomes aligned with deterministic outcomes. Conclusion:Given the use of Japan-specific data in the cost-effectiveness model, it is expected that the use of lenvatinib as a first-line treatment in Japan will be associated with cost savings and improved clinical outcomes versus sorafenib for patients with unresectable HCC.

Cost-Effectiveness Analysis of Five Systemic Treatments for Unresectable Hepatocellular Carcinoma in China: An Economic Evaluation Based on Network Meta-Analysis

“…Cai et al (31) confirmed that lenvatinib was economical compared to sorafenib when considered donations. Relevant literature outside of China (29,(32)(33)(34) showed that ICERs of lenvatinib and T + A compared with sorafenib were significantly higher than the threshold in China, which indicated that lenvatinib and T + A were not more cost-effective than sorafenib in China.…”

“…With no direct randomized controlled trials between groups of drugs, indirect comparisons are necessary. Most previous studies (18,29,(32)(33)(34)(35)(36)(37)(38) have used a common control drug as a bridge and adopted the constant HR assumption. This method requires that the KM curves of the test group and control group obey the assumption of equal proportions.…”

Cost-effectiveness analysis of sintilimab plus bevacizumab biosimilar compared with lenvatinib as the first-line treatment of unresectable or metastatic hepatocellular carcinoma

“…There have been several published economic evaluations of lenvatinib in different settings; however, they mainly compared lenvatinib with sorafenib. These analyses showed that across the world, including Japan [22,23], Australia [19], Canada [18,24], and China [25], lenvatinib is more cost-effective than sorafenib for HCC patients. Wen et al [26] and Su et al [27] focused on the cost-effectiveness of an ICI plus a VEGF inhibitor vs. a tyrosine kinase inhibitor (atezolizumab plus bevacizumab vs. sorafenib) for the treatment of advanced HCC in China.…”

Efficacy of immune checkpoint inhibitors plus molecular targeted agents after the progression of lenvatinib for advanced hepatocellular carcinoma

“…In our study, the ICI+Lenva and ICI+Others groups had similar follow-up periods and comparable baseline characteristics, and no significant differences were observed between these two groups in the short-term and long-term efficacy endpoints. In addition, lenvatinib performed well in a cost-effectiveness analysis (25)(26)(27)(28)(29), so the rechallenge of lenvatinib plus ICI is likely to be a better choice. Future prospective clinical trials are needed to prove the above hypothesis.…”