基于Markov模型的纳武利尤单抗治疗化疗后失败的进展期胃癌的成本效果分析

目的:评价近期在国内批准上市的纳武利尤单抗治疗化疗后失败的进展期胃癌的成本效果。方法:采用ATTRACTION-2临床试验所获数据(纳武利尤单抗组330例,安慰剂组163例),建立Markov模型模拟化疗失败后进展期胃癌的疾病过程。分析每组的成本、生命年(LY)以及质量调整生命年(QALY),然后计算增量成本效果比(ICER),并根据程序性细胞死亡配体1(PD-L1)的表达进行了亚组分析。运用敏感度分析对参数进一步评估,评价模型的稳定性。结果:PD-L1阳性的患者中,纳武利尤单抗组总健康产出值0.357QALY(0.526LY),总成本221171元;安慰剂组总健康产值0.251QALY(0.368LY),总成本40866元,纳武利尤单抗组相比安慰剂组的ICER为1700991元/QALY。PD-L1阴性的患者中,纳武利尤单抗组总健康产出值0.545QALY(0.845LY),总成本333195元;安慰剂组总健康产出值为0.403QALY(0.63LY),总成本为90285元,纳武利尤单抗组相比安慰剂组的ICER为1710634元/QALY。两亚组中纳武利尤单抗的ICER均大于意愿支付值(178980元)。概率敏感度分析显示,纳武利尤单抗具有成本效果性的概率为0。一元敏感度分析提示纳武利尤单抗的价格对结果影响最大。结论:在当前中国医疗保障角度下,纳武利尤单抗对比安慰剂在化疗失败的晚期胃癌患者治疗中不具有成本效果性,但是纳武利尤单抗可以为这些患者带来生存获益,通过开展慈善援助计划、纳入医保等措施可以提高其经济性。

Cost-effectiveness analysis of nivolumab in treatment of chemotherapy-refractory advanced gastric cancer based on Markov model

Objective: To evaluate the cost-effectiveness of nivolumab that has recently been approved for sale in China in treatment of chemotherapy-refractory advanced gastric cancer.  Methods: Using the data obtained from the ATTRACTION-2 trial (330 cases for nivolumab group, and 163 cases for placebo group), Markov model was created for simulation of the disease development process of chemotherapy-refractory advanced gastric cancer. The costs, life-years (LY) and quality-adjusted life-years (QALY) in each group were analysed, then the incremental cost-effectiveness ratio (ICER) was calculated to evaluate the cost-effectiveness, and subgroup analysis was also performed based on the expression of programmed death-ligand 1 (PD-L1). The variables were further valued by sensitivity analysis to assess the reliability of the model. Results: Among PD-L1 positive patients, the overall health output gained in nivolumab group was 0.357 QALY (0.526 LY) at a cost of 221 171 yuan, and in placebo group was 0.251 QALY (0.368 LY) at a cost of 40 866 yuan; the ICER for the nivolumab group compared with placebo group was 1 700 991 yuan/QALY. Among PD-L1 negative patients, the overall health output gained in nivolumab group was 0.545 QALY (0.845 LY) at a cost of 333 195 yuan, and in placebo group was 0.403 QALY (0.63 LY) at a cost of 90 285 yuan; the ICER for the nivolumab group compared with placebo group was 1 710 634 yuan/QALY. The ICER values of nivolumab treatment were greater than that of willingness-to-pay (178 980 yuan) in both subgroups. The probabilistic sensitivity analysis showed that the possibility of cost-effectiveness of nivolumab was 0. One-way sensitivity analysis indicated that the most influential parameter was the price of nivolumab. Conclusion: Nivolumab does not achieve cost-effectiveness compared to placebo for chemotherapy-refractory advanced gastric cancer at current health care environment in China. However, nivolumab can provide a survival benefit to the patients, and its economical effectiveness can be improved by means such as implementing charity care program and medical insurance coverage.