Cost-effectiveness of Osimertinib in the First-Line Treatment of Patients With EGFR-Mutated Advanced Non-Small Cell Lung Cancer
Cost-effectiveness of Osimertinib in the First-Line Treatment of Patients With EGFR-Mutated Advanced Non-Small Cell Lung Cancer
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DOI：
10.1001/jamaoncol.2018.1395
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发表时间：
2018-08-01
期刊：
影响因子：
28.4
通讯作者：
Lopes, Gilberto de Lima, Jr.
中科院分区：
文献类型：
--
作者：
Aguiar, Pedro N., Jr.;Haaland, Benjamin;Lopes, Gilberto de Lima, Jr.
重要性具有表皮生长因子受体(EGFR)基因突变的晚期非小细胞肺癌(NSCLC)患者的生存率在过去十年中随着靶向酪氨酸激酶抑制剂(TKIs)的开发而显著提高。Osimertinib是一种被美国食品和药物管理局批准用于治疗发生EGFR T790M突变的患者的第三代TKI，最近显示出与吉非替尼和厄洛替尼相比，对于未接受治疗的患者，Osimertinib的临床结果更好。目的本研究的目的是评估Osimertinib用于EGFR突变的NSCLC.DESIGN患者一线治疗的成本-效果，设置和参与者进行成本-效果分析，我们从Flaura随机临床试验中提取了单个患者的数据，并使用我们早期荟萃分析的结果来开发决策分析模型，并确定了奥西美替尼(AZD9291)与第一代和第二代EGFR-TKI在10年时间范围内的成本效益。所有的直接成本都是基于美国和巴西支付者的观点。主要结果和措施本研究的主要结果是在未治疗的EGFR突变的非小细胞肺癌中，使用osimertinib与第一代或第二代EGFR-TKI相比，以每质量调整寿命年获得的成本表示的增量成本-效果比(ICER)。结果在基础病例中，使用Flaura试验报告的数据，与第一代和第二代EGFR-TKI相比，osimertinib的QALY增加了0.594。在美国，奥西美替尼ICER为226 527美元对厄洛替尼，231 123美元对吉非替尼，219 874美元对法替尼。在巴西，ICER分别为162 329美元、180 804美元和175 432美元。Flaura试验中报告的总存活率(95%CI)(风险比0.63；95%CI，0.45-0.88)与ICER(从84342美元到859771美元)有最强的相关性。Osimertinib价格调整提高了Flaura试验数据的成本效益。例如，与基础病例ICER相比，osimertinib获取成本折扣10%与ICER降低20%相关，与基础病例ICER相比osimertinib获取成本折扣20%与ICER降低40%相关。结论根据世界卫生组织的成本效果阈值标准，根据当前成本和相关性，osimertinib对于美国或巴西的EGFR突变NSCLC一线治疗是不划算的。
IMPORTANCE The survival of patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene mutations has improved substantially in the last decade with the development of targeted tyrosine kinase inhibitors (TKIs). Osimertinib, a third-generation TKI that is approved by the US Food and Drug Administration for the treatment of patients who develop EGFR T790M mutations, has recently shown improved clinical outcomes compared with gefitinib and erlotinib for treatment-naive patients.OBJECTIVE The aim of this study was to assess the cost-effectiveness of osimertinib for the first-line treatment of patients with EGFR-mutated NSCLC.DESIGN, SETTING, AND PARTICIPANTS For this cost-effectiveness analysis, we extracted individual patient data from the FLAURA randomized clinical trial and used findings of our earlier meta-analysis to develop a decision-analytic model and determine the cost-effectiveness of osimertinib (AZD9291) compared with first-and second-generation EGFR-TKIs over a 10-year time horizon. All direct costs were based on US and Brazilian payer perspectives.MAIN OUTCOMES AND MEASURES The main outcome of this study was the incremental cost-effectiveness ratio (ICER) expressed as cost per quality-adjusted life-year (QALY) gained by using osimertinib compared with first-or second-generation EGFR-TKIs in previously untreated EGFR-mutated NSCLC.RESULTS In the base case using the data as reported in the FLAURA trial, the incremental QALY for osimertinib was 0.594 compared with the first-and second-generation EGFR-TKIs. In the United States, the osimertinib ICERs were $226 527 vs erlotinib, $231 123 vs gefitinib, and $219 874 vs afatinib. In Brazil, the ICERs were $162 329, $180 804, and $175 432, respectively. The overall survival (95% CI) reported in the FLAURA trial (hazard ratio, 0.63; 95% CI, 0.45-0.88) had the strongest association with the ICER (ranging from $84 342 to $859 771). Osimertinib price adjustments to the FLAURA trial data improved cost-effectiveness. For example, a discount of 10% on osimertinib acquisition cost was associated with a 20% decreased ICER compared with the base case ICER, and a discount of 20% on osimertinib acquisition cost was associated with a 40% decreased ICER compared with the base case ICER.CONCLUSIONS AND RELEVANCE At current costs, by World Health Organization cost-effectiveness threshold criteria, osimertinib is not cost-effective for first-line therapy of EGFR-mutated NSCLC in either the United States or Brazil.