Background and ObjectiveUnresectable hepatocellular carcinoma (uHCC) is the main histological subtype of liver cancer and causes a great disease burden in China. We aimed to evaluate the cost-effectiveness of five first-line systemic treatments newly approved in the Chinese market for the treatment of uHCC, namely, sorafenib, lenvatinib, donafenib, sintilimab plus bevacizumab (D + A), and atezolizumab plus bevacizumab (T + A) from the perspective of China's healthcare system, to provide a basis for decision-making.MethodsWe constructed a network meta-analysis of 4 clinical trials and used fractional polynomial models to indirectly compare the effectiveness of treatments. The partitioned survival model was used for cost-effectiveness analysis. Primary model outcomes included the costs in US dollars and health outcomes in quality-adjusted life-years (QALYs) and the incremental cost-effectiveness ratio (ICER) under a willingness-to-pay threshold of $33,521 (3 times the per capita gross domestic product in China) per QALY. We performed deterministic and probabilistic sensitivity analyses to investigate the robustness. To test the effect of active treatment duration on the conclusions, we performed a scenario analysis.ResultsCompared with sorafenib, lenvatinib, donafenib, D + A, and T + A regimens, it yielded an increase of 0.25, 0.30, 0.95, and 1.46 life-years, respectively. Correspondingly, these four therapies yielded an additional 0.16, 0.19, 0.51, and 0.86 QALYs and all four ICERs, $40,667.92/QALY gained, $27,630.63/QALY gained, $51,877.36/QALY gained, and $130,508.44/QALY gained, were higher than $33,521 except for donafenib. T + A was the most effective treatment and donafenib was the most economical option. Sensitivity and scenario analysis results showed that the base-case analysis was highly reliable.ConclusionAlthough combination therapy could greatly improve patients with uHCC survival benefits, under the current WTP, donafenib is still the most economical option.
