DataSheet1_Immune Checkpoint Inhibitors Plus an Anti-VEGF Antibody as the First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Network Meta-Analysis and Cost-Effectiveness Analysis.docx

Background: Sintilimab + a bevacizumab biosimilar (IBI305) (SB) and atezolizumab + bevacizumab (AB) have been approved for the treatment of unresectable hepatocellular carcinoma (HCC). At present, oncologists and their patients remain indecisive on their preferred treatment regime. Therefore, assessing their efficacy via a network meta-analysis and determining their comparative cost-effectiveness is necessary.
Objective: To evaluate the cost-effectiveness of SB and AB compared with sorafenib alone for the treatment of unresectable HCC.
Materials and Methods: The data used in our analysis were obtained from patients in ORIENT-32 and IMbrave150 phase III randomized clinical trials. A Bayesian network meta-analysis and cost-effectiveness analysis that included 1,072 patients were performed in this study. A partitioned survival model was applied to the patients with unresectable HCC. The model was designed with a 15-year time horizon, 1-month cycle, and 5% discount rate for costs and outcomes. In China, an incremental cost-effectiveness ratio (ICER) value of less than $33,500 (three times the GDP per capita in 2020) per quality-adjusted life-year (QALY) is considered cost-effective. The influence of parameter uncertainty on the results was verified by one-way deterministic sensitivity analysis and probability sensitivity analysis. Furthermore, scenario analyses of the patient assistance program (PAP) were conducted to explore the cost-effectiveness of SB and AB.
Results: For the model of 1,072 patients, treatment with SB produced an additional 0.617 QALYs compared with sorafenib, resulting in an ICER of $39,766.86/QALY. Similarly, treatment with AB produced an additional 0.596 QALYs compared with sorafenib, resulting in an ICER of $103,037.66/QALY. The probability sensitivity analysis showed that when the willingness-to-pay (WTP) threshold was $33,500/QALY, the cost-effectiveness of SB and AB was 15.4 and 0.4%, respectively. However, in the scenario analyses, the probability of SB and AB regimens being cost-effective was 65.4 and 15.8%, respectively, at a WTP of $33,500/QALY.
Conclusion: The findings from our study showed that sintilimab + a bevacizumab biosimilar is a cost-effective regimen compared with sorafenib as the first-line therapy for unresectable HCC in China at a $33,500 WTP threshold if sintilimab PAP is considered. However, the atezolizumab + bevacizumab regimen is not cost-effective whether atezolizumab PAP is considered or not.

背景：信迪利单抗（Sintilimab）联合贝伐珠单抗生物类似药（bevacizumab biosimilar）IBI305（简称SB）与阿替利珠单抗（atezolizumab）联合贝伐珠单抗（简称AB）均已获批用于不可切除肝细胞癌（unresectable hepatocellular carcinoma, HCC）的治疗。目前，肿瘤医师与患者仍对二者的治疗方案选择存在犹豫。因此，通过网状meta分析评估其疗效并比较二者的成本-效果具有重要意义。

目的：评估SB、AB对比单用索拉非尼（sorafenib）治疗不可切除HCC的成本-效果。

材料与方法：本分析所用数据来源于ORIENT-32与IMbrave150两项III期随机临床试验的受试者。本研究纳入1072例患者，开展了贝叶斯网状meta分析与成本-效果分析。针对不可切除HCC患者，本研究采用分区生存模型，设定15年模拟时限、1个月为循环周期，并对成本与结局采用5%的贴现率。在中国，每获得1个质量调整生命年（quality-adjusted life-year, QALY）的增量成本效果比（incremental cost-effectiveness ratio, ICER）低于33500美元（为2020年人均GDP的3倍）即被视为具有成本-效果。本研究通过单因素确定性敏感性分析与概率敏感性分析验证了参数不确定性对研究结果的影响。此外，本研究还开展了患者援助项目（patient assistance program, PAP）情景分析，以探索SB与AB的成本-效果情况。

结果：在针对1072例患者的模型中，与单用索拉非尼相比，SB治疗可额外获得0.617个QALY，对应的ICER为39766.86美元/QALY。同理，AB治疗较单用索拉非尼可额外获得0.596个QALY，对应的ICER为103037.66美元/QALY。概率敏感性分析结果显示，当支付意愿（willingness-to-pay, WTP）阈值设定为33500美元/QALY时，SB与AB的成本-效果概率分别为15.4%与0.4%。但在情景分析中，当WTP阈值为33500美元/QALY时，SB与AB治疗方案具备成本-效果的概率分别升至65.4%与15.8%。

结论：本研究结果表明，在中国，当WTP阈值为33500美元/QALY且纳入信迪利单抗患者援助项目时，信迪利单抗联合贝伐珠单抗生物类似药作为不可切除HCC的一线治疗方案，对比索拉非尼具备成本-效果。然而，无论是否纳入阿替利珠单抗患者援助项目，阿替利珠单抗联合贝伐珠单抗方案均不具备成本-效果。