Cost-Effectiveness Analysis of Five Systemic Treatments for Unresectable Hepatocellular Carcinoma in China: An Economic Evaluation Based on Network Meta-Analysis

Abstract

Background and objective: Unresectable 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.

Methods: We 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.

Results: Compared 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.

Conclusion: Although combination therapy could greatly improve patients with uHCC survival benefits, under the current WTP, donafenib is still the most economical option.

Keywords: cost-effectiveness analysis; fractional polynomial; network meta-analysis; partitioned survival; unresectable hepatocellular carcinoma.

Figure 1

Model structure of a decision tree combining the partitioned survival model. (HCC, hepatocellular carcinoma; P, progression-free survival; D + A, sintilimab plus bevacizumab; T + A, atezolizumab plus bevacizumab).

Figure 2

One-way sensitivity analysis chart. (C_AT, unit price of atezolizumab; C_BED, unit price of bevacizumab (D + A group); C_BEA, unit price of bevacizumab (T + A group); C_DO, unit price of donafenib; C_LE, unit price of lenvatinib; C_RE, unit price of regorafenib; C_SF, unit price of sorafenib; DR_inAT, dosage density of T + A; DR_inLE, dosage density of lenvatinib; DR_inSIN, dosage density of D + A; d0_os_das, OS HR (D + A vs sorafenib); d0_os_ds, OS HR (donafenib vs sorafenib);d0_os_ls, OS HR (lenvatinib vs sorafenib); d0_os_ts, OS HR (T + A vs sorafenib); d0_pfs_das, PFS HR (D + A vs sorafenib); d0_pfs_ds, PFS HR (donafenib vs sorafenib); d0_pfs_ts, PFS HR (T + A vs sorafenib); ME_SOS, theta for lognormal model of OS (sorafenib); ME_SPFS, theta for lognormal model of PFS (sorafenib); SD_SOS, sigma for lognormal model of OS (sorafenib); SD_SPFS, sigma for lognormal model of PFS (sorafenib); SE_DOR, probability of TKIs therapy after donafenib progression; SE_LER, probability of TKIs therapy after levatinib progression; SE_SINR, probability of TKIs therapy after D + A progression; SE_SORR, probability of TKIs therapy after sorafenib progression; U_PFS, utility for PFS; U_PD, utility for PD).

Figure 3

Base-case probabilistic sensitivity analysis: scatter plot (10,000 iterations).

Figure 4

Base-case probabilistic sensitivity analysis: cost-effectiveness acceptability curve (10,000 iterations).