OBJECTIVES : Although the efficacy and safety of Regorafenib as a second-line treatment for advanced hepatocellular carcinoma (HCC) patients were confirmed in RESOURCE, a randomized and placebo-controlled phase 3 trial, its societal value has not been assessed properly. This study aimed to evaluate the cost-effectiveness of Regorafenib for advanced HCC patients following Sorafenib treatment compared with best supportive care (BSC) in the third-party payer’s and the U.S. societal perspectives.

METHODS : A Markov model with a five-year horizon and one month cycle was simulated using the clinical data of RESOURCE. Possible health transitions reflected three states (Stable disease, Progressive disease, and Death). The third-party payer’s perspective analysis was conducted based on costs of managing patients and out-of-pocket costs. In the societal perspective analysis, time costs of informal caregivers and non-time costs were considered additionally. All costs were measured in 2017 USD. QALYs were calculated based on EQ-5D. A 3% time discount rate was used in the societal perspective analysis and 7% in the third-party payer’s analysis.

RESULTS : Incremental QALYs for Regorafenib compared to BSC was 0.12 (0.51 vs 0.39). Total costs was $33,434 higher in Regorafenib from the societal perspective ($65,901 vs $ 32,467). Thus, ICERs was $ 277,463/QALY, which exceeds a U.S. societal willingness-to-pay (WTP) of $150,000. One-way sensitivity analysis ($206,740/QALY ~ $509,485/QALY) demonstrated that ICER was sensitive to the overall survival of Regorafenib and BSC and daily dose of Regorafenib. According to probabilistic sensitivity analysis, the likelihood of Regorafenib being cost-effective was shown to be 4.7% and would not reach 50% otherwise WTP increased up to $270,000.

CONCLUSIONS : Regorafenib is not a cost-effective alternative to BSC for patients with advanced HCC from the U.S. societal perspective. The sensitivity analyses indicate that this result is robust.