酪氨酸激酶抑制剂 (吉非替尼、厄洛替尼、阿法替尼和奥希替尼)一线治疗表皮生长因子受体突变的晚期非小细胞肺癌的成本-效果分析

doi:10.5246/jcps.2021.03.021

中国药学(英文版) ›› 2021, Vol. 30 ›› Issue (3): 253-263.DOI: 10.5246/jcps.2021.03.021

酪氨酸激酶抑制剂 (吉非替尼、厄洛替尼、阿法替尼和奥希替尼)一线治疗表皮生长因子受体突变的晚期非小细胞肺癌的成本-效果分析

骆少红¹, 董凉凉¹, 李逸元¹, 徐丹², 陈敏³^,^*()

1. 福建医科大学附属第一医院药学部, 福建福州 350005
2. 福建省立金山医院药学部, 福建福州 350028
3. 福建医科大学省立临床医学院; 福建省立医院药学部, 福建福州 350001

收稿日期:2020-12-24 修回日期:2021-01-15 接受日期:2021-02-05 出版日期:2021-03-29 发布日期:2021-03-29
通讯作者: 陈敏
作者简介:
+ Tel.: +86-13960787789, E-mail: chenmin163com@163.com

Cost-effectiveness analysis of tyrosine kinase inhibitors (erlotinib, gefitinib, afatinib and osimertinib) as first-line therapy for epidermal growth factor receptor-mutated advanced non-small cell lung cancer

Shaohong Luo¹, Liangliang Dong¹, Yiyuan Li¹, Dan Xu², Min Chen³^,^*()

1 Department of Pharmacy, First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China
2 Department of Pharmacy, Fujian Provincial Jinshan Hospital, Fuzhou 350028, China
3 Clinical College of Fujian Medical University Provincial Hospital; Department of Pharmacy, Fujian Provincial Hospital, Fuzhou 350001, China

Received:2020-12-24 Revised:2021-01-15 Accepted:2021-02-05 Online:2021-03-29 Published:2021-03-29
Contact: Min Chen

摘要/Abstract

摘要：

吉非替尼、厄洛替尼、阿法替尼和奥希替尼已被推荐为表皮生长因子受体突变的晚期非小细胞肺癌的一线治疗药物, 但同时比较这四种酪氨酸激酶抑制剂在中国的经济性目前尚无研究。本研究旨在评价吉非替尼、厄洛替尼、阿法替尼和奥希替尼一线治疗表皮生长因子受体突变的晚期非小细胞肺癌的成本-效果性。通过构建马尔科夫模型, 从中国医疗系统角度评价四种酪氨酸激酶抑制剂对初治的表皮生长因子受体突变的晚期非小细胞肺癌患者的影响。临床数据和效用值来源于文献, 成本来源于中国官方网站。主要结局指标为增量-成本效果比, 通过敏感性分析检验模型的稳健性。研究发现阿法替尼治疗成本最低, 生存获益最少; 奥希替尼治疗成本最高, 生存获益最大。与阿法替尼相比, 吉非替尼每多获得一个质量调整生命年需多花费732美元, 该数值低于29 382美元/每质量调整生命年的意愿支付阈值。与吉非替尼相比, 厄洛替尼治疗成本更高但生存时间更短, 因此被认为是劣势方案。奥希替尼与吉非替尼比较的增量-成本效果比为71 330美元/每质量调整生命年, 超过意愿支付阈值。这表明, 从中国医疗系统角度来看, 吉非替尼是表皮生长因子受体突变晚期非小细胞肺癌一线治疗中性价比最高的方案。降低奥希替尼的价格或将意愿支付阈值提高到68 558美元/每质量调整生命年可能可以提高奥希替尼的经济性。单因素敏感性分析表明该模型是稳健的。

关键词: 成本-效果分析, 马尔科夫模型, 酪氨酸激酶抑制剂, 非小细胞肺癌, 一线治疗, 表皮生长因子受体

Abstract:

Gefitinib, erlotinib, afatinib and osimertinib have been recommended as the first-line treatment for epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC), whereas no studies have compared the cost-effectiveness of these four tyrosine kinase inhibitors (TKIs) simultaneously in China. In the present study, we aimed to estimate the cost-effectiveness of erlotinib, gefitinib, afatinib and osimertinib for untreated EGFR-mutated advanced NSCLC. A Markov model was constructed to compare the 10-year impact of four TKIs for patients with treatment-naive EGFR-mutated advanced NSCLC from the perspective of the Chinese medical system. Clinical data and utility values were derived from published literature, and costs were obtained from Chinese official websites. The primary output indicator was the incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed to test the robustness of the model. We found that afatinib was estimated to spend the lowest cost with minimum life-years (LYs), while osimertinib was the most expensive regimen with maximum LYs. The ICER of gefitinib versus afatinib was \$732/quality-adjusted life-year (QALY), which was less than the willingness-to-pay (WTP) of \$29 382/QALY. Compared with gefitinib, erlotinib yielded a higher cost and a shorter lifetime, hence it was identified as a dominated strategy. Then, osimertinib was compared to gefitinib, which produced an ICER of \$71 330/QALY, exceeding the WTP. It suggested that gefitinib was the most cost-effective regimen as the first-line treatment for EGFR-mutated advanced NSCLC. Decreasing the osimertinib price or increasing the WTP threshold to \$68 558/QALY might enhance the favorability of the outcome, by which osimertinib might become more cost-effective. One-way sensitivity analysis manifested that the model was robust.

Key words: Cost-effectiveness analysis, Markov model, Tyrosine kinase inhibitor, Non-small cell lung cancer, First-line therapy, Epidermal growth factor receptor

Supporting:

骆少红, 董凉凉, 李逸元, 徐丹, 陈敏. 酪氨酸激酶抑制剂 (吉非替尼、厄洛替尼、阿法替尼和奥希替尼)一线治疗表皮生长因子受体突变的晚期非小细胞肺癌的成本-效果分析[J]. 中国药学(英文版), 2021, 30(3): 253-263.

Shaohong Luo, Liangliang Dong, Yiyuan Li, Dan Xu, Min Chen. Cost-effectiveness analysis of tyrosine kinase inhibitors (erlotinib, gefitinib, afatinib and osimertinib) as first-line therapy for epidermal growth factor receptor-mutated advanced non-small cell lung cancer[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(3): 253-263.

图/表 9

Figure 1. Potential treatment sequences in EGFR mutation-positive NSCLC. EGFR: epidermal growth factor receptor; NSCLC: non-small cell lung cancer; BSC: best supportive care.

Figure 2. Markov state transition model.

Table 1. Key clinical data inputted to model.

Table 2. Costs of drug and examinations.

Table 3. Utility values of different health states and probability of SAEs.

Table 4. Sensitivity analysis of parameter ranges and distribution.

Table 5. Summary of cost and outcome results.

Figure 3. Tornado diagram for one-way sensitivity analysis: (a) gefitinib vs. afatinib; (b) osimertinib vs. gefitinib. QALYs: quality-adjusted life years; ICER: incremental cost-effectiveness ratio; BSC: best supportive care; PFS: progression-free survival; PD: progressive disease; AEs: adverse effects; G: gefitinib; E: erlotinib; A: afatinib.

Figure 4. Cost-effectiveness acceptability curve. WTP: willingness-to-pay.

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酪氨酸激酶抑制剂 (吉非替尼、厄洛替尼、阿法替尼和奥希替尼)一线治疗表皮生长因子受体突变的晚期非小细胞肺癌的成本-效果分析

Cost-effectiveness analysis of tyrosine kinase inhibitors (erlotinib, gefitinib, afatinib and osimertinib) as first-line therapy for epidermal growth factor receptor-mutated advanced non-small cell lung cancer

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