Cost-effectiveness of first-line systemic therapies for unresectable hepatocellular carcinoma

To examine the cost-effectiveness of first-line systemic therapies recommended by the National Comprehensive Cancer Network guidelines for Unresectable Hepatocellular Carcinoma (uHCC) from the US social and payer's perspective. A cost-effectiveness analysis was conducted using a three-state partitioned survival model to assess the cost-effectiveness of atezolizumab plus bevacizumab, tremelimumab plus durvalumab, durvalumab, lenvatinib and sorafenib as first-line treatments for uHCC. Clinical efficacy was derived from a published network meta-analysis. Cost and utility inputs were collected from literature. Main outcomes measured were quality-adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER). Univariate and probabilistic sensitivity analyses, as well as scenario analyses were performed. Over a 10-year time horizon, atezolizumab plus bevacizumab yielded the highest QALYs. Compared to sorafenib, atezolizumab plus bevacizumab, tremelimumab plus durvalumab and lenvatinib had ICERs of $196 704/QALY, $800 755/QALY and $2 032 756/QALY, respectively. Sorafenib was dominated by durvalumab due to lower QALYs and higher costs. At a willingness-to-pay threshold of $150 000/QALY, probabilistic sensitivity analysis revealed that durvalumab had a 99.96% probability of providing the highest net monetary benefit. At a willingness-to-pay threshold of $150 000/QALY, durvalumab is likely the most cost-effective first-line systemic therapy for uHCC compared to sorafenib. Although atezolizumab plus bevacizumab yielded the highest QALYs, their ICERs exceeded the commonly accepted cost-effectiveness threshold ($150 000$ per QALY gained). These findings can inform clinical decision-making, resource allocation and future research priorities in managing uHCC.