Comprehensive Unit for Health Economic Evidence Review and Decision Support (CHEERS), Research Organization of Science and Technology, Ritsumeikan University, #215, Kyoto Research Park Bld. No. 6, 93 Awata-machi, Chudoji, Shimogyo-ku, Kyoto, 600-8815, Japan.
Comprehensive Unit for Health Economic Evidence Review and Decision Support (CHEERS), Research Organization of Science and Technology, Ritsumeikan University, #209, Research Park Bid. No.2, 134, Minamimachi, Chudoji, Simogyo-ku, Kyoto, 600-8813, Japan.
Clin Drug Investig. 2022 Jul;42(7):599-609. doi: 10.1007/s40261-022-01168-0. Epub 2022 Jun 8.
In Japan, indications for nivolumab have been expanded to include the combination therapy with ipilimumab in various cancers. This study aimed to evaluate the cost-effectiveness of combination therapy of nivolumab plus ipilimumab (NIV + IPI) for patients with advanced non-small-cell lung cancer (NSCLC), comparing it with platinum-doublet chemotherapy in Japanese settings.
A partitioned survival model was developed to predict costs and quality-adjusted life-years (QALYs) in a NIV + IPI arm and a chemotherapy arm. Data on overall survival and progression-free survival were derived from the CheckMate 227 trial. Cost estimates were based on a Japanese healthcare system perspective using real-world data from the JMDC claims database. Utilities were derived from published sources outside Japan. The incremental cost-effectiveness ratio (ICER) of NIV + IPI therapy compared with chemotherapy was estimated. A scenario analysis on the level of programmed death-ligand 1 (PD-L1) expression was conducted. In addition, sensitivity analyses were performed to assess the uncertainty in parameter settings.
Compared with chemotherapy, NIV + IPI therapy incurred an additional cost of USD102,623 and conferred an additional 1.007 QALY, which resulted in an ICER of USD101,950/QALY gained. Contrary to prior expectations, the ICER of patients with a PD-L1 expression level ≥ 1% was higher than that of patients with a PD-L1 expression level < 1% (USD145,868/QALY and USD127,737/QALY, respectively). Sensitivity analyses showed a relatively robust result with the ICERs remaining higher than a Japanese price adjustment threshold of USD75,000/QALY with a few exceptions.
The combination of NIV + IPI as first-line therapy would not be cost effective under a willingness-to-pay threshold of USD75,000/QALY from the perspective of the Japanese healthcare system.
在日本，纳武利尤单抗的适应证已扩大到包括与伊匹单抗联合用于各种癌症。本研究旨在评估纳武利尤单抗联合伊匹单抗（NIV+IPI）联合疗法用于晚期非小细胞肺癌（NSCLC）患者的成本效果，与日本环境下的铂类双联化疗进行比较。
采用分割生存模型预测 NIV+IPI 组和化疗组的成本和质量调整生命年（QALY）。总生存和无进展生存数据来源于 CheckMate 227 试验。成本估算基于 JMDC 索赔数据库中的真实世界数据，从日本医疗保健系统的角度出发。效用值来源于日本以外的已发表资料。对 NIV+IPI 治疗与化疗相比的增量成本效果比（ICER）进行了估计。对程序性死亡配体 1（PD-L1）表达水平进行了情景分析。此外，还进行了敏感性分析，以评估参数设置的不确定性。
与化疗相比，NIV+IPI 治疗增加了 102623 美元的额外成本，并带来了 1.007 个 QALY，导致 ICER 为 101950 美元/QALY。与之前的预期相反，PD-L1 表达水平≥1%的患者的 ICER 高于 PD-L1 表达水平<1%的患者（分别为 145868 美元/QALY 和 127737 美元/QALY）。敏感性分析显示，除少数例外，在日本 75000 美元/QALY 的价格调整阈值下，ICER 仍然较高，结果相对稳健。
从日本医疗保健系统的角度来看，在愿意支付 75000 美元/QALY 的阈值下，纳武利尤单抗联合伊匹单抗作为一线治疗的方案不具有成本效果。
