Cost-effectiveness analysis of lenvatinib treatment for patients with unresectable hepatocellular carcinoma (uHCC) compared with sorafenib in Japan

Abstract

Background: Lenvatinib demonstrated a treatment effect on overall survival by the statistical confirmation of non-inferiority to sorafenib for the first-line treatment of uHCC. The objective of this study was to evaluate the cost-effectiveness of lenvatinib compared with sorafenib for patients with uHCC in Japan.

Methods: A partitioned-survival model was developed to estimate the cost-effectiveness of lenvatinib versus sorafenib when treating uHCC patients over a lifetime horizon and considering total public healthcare expenditure. Efficacy and safety data were extracted from the REFLECT trial. Utility values were derived from the European Quality-of-Life 5-Dimension Questionnaire, conducted with patients enrolled in the REFLECT trial. Direct medical costs, such as primary drug therapy, outpatient visits, diagnostic tests, hospitalization, post-progression therapy, and adverse-event treatments, were included. Cost parameters unavailable in the clinical trial or publications were obtained based on the consolidated clinical standards from a Delphi panel of four Japanese medical experts.

Results: For lenvatinib versus sorafenib, the incremental cost was - 406,307 Japanese Yen (JPY), and the incremental life years and quality-adjusted life years (QALYs) were 0.27 and 0.23, respectively. Thus, lenvatinib dominated sorafenib, due to the mean incremental cost-effectiveness ratio falling in the fourth quadrant, conferring more benefit at lower costs compared with sorafenib. The probabilistic sensitivity analysis showed that 81.3% of the simulations were favorable to lenvatinib compared with sorafenib, with a payer's willingness-to-pay-per-QALY of 5 million JPY.

Conclusions: Lenvatinib was cost-effective compared with sorafenib for the first-line treatment of uHCC in Japan.

Keywords: Cost-effectiveness; Hepatocellular carcinoma; Lenvatinib; QALY; Sorafenib.

Fig. 1

Breakdown of costs in the base case

Fig. 2

Deterministic sensitivity analysis (a), probabilistic sensitivity analysis (b), and cost-effectiveness acceptability curves (c), in lenvatinib compared to sorafenib. In a PSA, using a set of input parameter values drawn 1000 times by random sampling from each distribution, the model generates 1000 outcomes appeared as a “cloud” of potential outcomes (b), or graphed as a proportion in CEAC (c). b Visibly shown the four quadrants that the outcomes (i.e., ICER) can be fallen. The first quadrant is the area that lenvatinib is more effective (measured by QALY) and more costly compared with sorafenib. Similarly, the fourth quadrant is the area that lenvatinib is more effective and less costly compared with sorafenib. c tells that 81.3% of ICERs simulations fall the area considered cost-effective in relation to a given Japanese cost-effectiveness threshold of 5 million JPY per QALY. AFP alpha-fetoprotein, CT scan computed-tomography scan, ICER incremental cost-effectiveness ratio, INR prothrombin time and international normalized ratio, LEN lenvatinib, MRI magnetic resonance imaging, PIVKA-2 protein induced by vitamin K absence-II, QALY quality-adjusted life year, SOR sorafenib, WTP willingness-to-pay

Fig. 2

Deterministic sensitivity analysis (a), probabilistic sensitivity analysis (b), and cost-effectiveness acceptability curves (c), in lenvatinib compared to sorafenib. In a PSA, using a set of input parameter values drawn 1000 times by random sampling from each distribution, the model generates 1000 outcomes appeared as a “cloud” of potential outcomes (b), or graphed as a proportion in CEAC (c). b Visibly shown the four quadrants that the outcomes (i.e., ICER) can be fallen. The first quadrant is the area that lenvatinib is more effective (measured by QALY) and more costly compared with sorafenib. Similarly, the fourth quadrant is the area that lenvatinib is more effective and less costly compared with sorafenib. c tells that 81.3% of ICERs simulations fall the area considered cost-effective in relation to a given Japanese cost-effectiveness threshold of 5 million JPY per QALY. AFP alpha-fetoprotein, CT scan computed-tomography scan, ICER incremental cost-effectiveness ratio, INR prothrombin time and international normalized ratio, LEN lenvatinib, MRI magnetic resonance imaging, PIVKA-2 protein induced by vitamin K absence-II, QALY quality-adjusted life year, SOR sorafenib, WTP willingness-to-pay