Osimertinib使用於台灣表皮生長因子受器突變陽性晚期肺腺癌之成本效果分析

Cost-Effectiveness of Osimertinib in Taiwan for Epidermal Growth Factor Receptor Mutation Positive Advanced Lung Adenocarcinoma

陳柏諺(Po-Yen Chen)

指導教授 ： 陳崇鈺

共同指導教授 ： 許茜甯(Chien-Ning Hsu)

高雄醫學大學/藥學院/藥學系臨床藥學碩士班/碩士(2020年)

摘要

研究背景及目的
Osimertinib (Tagrisso，泰格莎)在臨床試驗中相較於既有治療方式具有顯著較佳臨床效果。然而目前對於osimertinib在現實世界中的成本效益仍然未知。本研究旨在從台灣健保體系與付費者的觀點評估osimertinib相較於現有的表皮生長因子受體酪氨酸激酶抑制劑使用於表皮生長因子受體突變之晚期肺腺癌病人一線治療的成本效益。
研究方法
使用台灣國家健康保險資料庫(2014至2017年)，世代追蹤研究設計比較成年病人首次使用表皮生長因子受體酪氨酸激酶抑制劑(gefitinib、erlotinib、afatinib)作為一線治療的生命年和直接醫療費用差異。Osimertinib的生命年資料參考臨床試驗結果，並以健保給付單價作為參考成本。以三種健康狀態: 無惡化存活、疾病惡化與死亡代表疾病進程。根據整體存活所觀察的生命年，使用代表台灣群體的文獻估值資料計算生活品質調整後生命年為四個表皮生長因子受體酪氨酸激酶抑制劑治療選項的療效評估指標。
相對成本效益評估期間包括資料庫追蹤的四年與模型推估的十年。以分區生存模型比較十年評估期間四個治療選項的總成本與生活品質調整後生命年。以2017年新台幣幣值，每年3%折現率的療效與成本進行遞增成本效果比值計算，並以世界衛生組織建議<1單位國內生產總值(NT$760,000)作為具成本效益的閾值。除了以中樞系統轉移進行分組分析，每項遞增成本效果比值皆以決定性敏感度分析與機率性敏感度分析測試模型的穩健性。
研究結果
本研究收錄共10,046名病人，其中3,649位接受gefitinib治療、3,310位接受erlotinib治療、3,041位接受afatinib治療。Gefitinib組無惡化存活期中位數為9.5個月、erlotinib組為9.7個月、afatinib組為11.5個月；整體存活期中位數分別為21.3、21.8和23.9個月。每位病人的終身治療總醫療費用平均為新台幣801,144、797,554和862,616元。
在四年的評估期間中，osimertinib相較於gefitinib、erlotinib和afatinib分別額外得到0.5、0.4和0.4個生活品質調整後生命年，增加的費用為新台幣3,283,706、3,230,367和3,094,619元，遞增成本效果比值分別為6,604,398、7,551,052元和7,866,921元。而在十年的評估期間中，osimertinib相較於其他表皮生長因子受體酪氨酸激酶抑制劑分別額外得到0.6、0.5、0.5個生活品質調整後生命年，增加的費用為新台幣3,996,554、4,041,424和3,683,301元以及遞增成本效果比值分別為6,657,873、7,485,712和7,941,010元。該模型的主要影響因素包括病人接受治療後於無惡化存活期之估值以及osimertinib的費用。
研究結論
根據世界衛生組織建議台灣成本效益閾值為一個國內生產總值新台幣760,000元的標準下，osimertinib相較早期表皮生長因子受體酪氨酸激酶抑制劑作為表皮生長因子受體突變晚期肺腺癌患者的第一線治療被認為是不符合成本效益。

關鍵字

成本效果分析 ； osimertinib ； 晚期肺腺癌 ； 表皮生長因子受體突變 ； 第一線治療

並列摘要

Introduction and objective
Osimertinib (Tagrisso) showed remarkable efficacy in clinical trials. However, the cost-effectiveness of osimertinib in real-world remains uncertain. The study aim was to evaluate the cost-effectiveness of osimertinib compared to existing epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in first-line treatment for patients with EGFR-mutated advanced lung adenocarcinoma from the perspective of Taiwan health insurance system.
Methods
The life-year (LY) gains and direct medical costs were ascertained among adult patients newly treated with first-line therapy of earlier-generation EGFR-TKIs (gefitinib, erlotinib, afatinib) using Taiwan national health insurance research database between 2014 and 2017. LYs of osimertinib was based on FLAURA trial and its reimbursement unit price was used as reference cost. Literature-based utility was used to calculate quality-adjusted life years (QALYs). Three health states (progression-free, progressive disease and death) were applied to represent the disease course and a partitioned survival analysis (PartSA) model was developed to compare total cost and QALYs of four treatments in a 10-year time horizon. Discount rate was set to annual 3% and sensitivity analyses tested the robustness of the model.
Results
A total of 10,046 patients were identified and 3,649 received gefitinib, 3,310 receive erlotinib and 3,041 receive afatinib. Median progression-free survival (PFS) was 9.5 months for gefitinib arm, 9.7 months for erlotinib and 11.5 months in afatinib arm; median OS were 21.3, 21.8, 23.9 months, respectively. Life-time total cost per person was NT$801,144, 797,554, and 862,616 in 2017 New Taiwan dollar value.
In 4-year time horizon, osimertinib compared with gefitinib, erlotinib, afatinib associated with additional 0.5, 0.4 and 0.4 QALYs with incremental costs of NT$3,283,706, 3,230,367 and 3,094,619. The incremental cost effectiveness ratios (ICERs) per QALY of osimertinib were NT$6,604,398, 7,551,052 and 7,866,921, respectively. Within 10-year period, the additional QALYs derived from osimertinib against other EGFR-TKIs were 0.6, 0.5, and 0.5 QALYs with incremental costs of NT$3,996,554, 4,041,424 and 3,683,301. The ICERs per QALY of osimertinib were NT$6,657,873, 7,485,712 and 7,941,010, respectively. The model was sensitive to the utility in progression-free period and osimertinib cost.
Conclusions
Osimertinib as a first-line treatment option for patients with EGFR mutant advanced lung adenocarcinoma is not a cost-effective alternative to earlier-generation of EGFR-TKIs according to WHO cost-effectiveness criteria of NT$760,000 (1 gross domestic product) threshold in Taiwan.

並列關鍵字

cost-effectiveness analysis ； osimertinib ； advanced lung adenocarcinoma ； EGFR mutation ； first-line treatment

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