OBJECTIVES Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in England. Lenvatinib (LEN) met the primary endpoint of non-inferiority in overall survival (OS) versus sorafenib (SOR) in the REFLECT trial, with a hazard ratio (HR) of 0.92 in favour of LEN (95% confidence interval [CI]: 0.79, 1.06), in patients with advanced or unresectable HCC (a/u HCC). However, baseline imbalances in the proportion of patients with AFP levels ≥200 ng/mL, and in HCV aetiology, may have favoured the SOR arm. After adjustment for baseline imbalances, the HR for OS was nominally superior in favour of LEN at 0.82 (95% CI: 0.70, 0.96). Economic analysis was undertaken to assess the cost-effectiveness of LEN versus SOR in the treatment of adults with untreated a/u HCC, from a UK healthcare system perspective.

METHODS A partitioned survival model was used to extrapolate costs and quality-adjusted life-years (QALYs) over a lifetime time horizon. Survival curves for progression-free survival (PFS) and OS were based on multivariable parametric models adjusting for imbalances in baseline characteristics and other key prognostic variables. Using multivariable parametric survival models improves precision, avoiding conditional bias from covariate imbalance. Utility values were derived from EQ-5D-3L data collected in REFLECT, and costs were taken from published sources.

RESULTS The model estimates a survival increase of 3.1 months with LEN, and incremental costs and QALYs of £8,541 and 0.18, respectively, resulting in an incremental cost-effectiveness ratio (ICER) of £48,494. A willingness to pay of £50,000 per QALY is assumed, which is an accepted UK threshold where end of life criteria apply.

CONCLUSIONS Using list prices, LEN represents a cost-effective use of NHS resources. Results were robust to changes in key assumptions when sensitivity analyses were performed.