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

Abstract Aims 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. Methods 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. Results 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. Conclusions 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.