Bertranou Evelina, Bodnar Carolyn, Dansk Viktor, Greystoke Alastair, Large Samuel, Dyer Matthew
a PAREXEL Access , London , UK.
b AstraZeneca , Cambridge , UK.
J Med Econ. 2018 Feb;21(2):113-121. doi: 10.1080/13696998.2017.1377718. Epub 2017 Sep 21.
This study presents the cost-utility analysis that was developed to inform the NICE health technology assessment of osimertinib vs platinum-based doublet chemotherapy (PDC) in patients with EGFR-T790M mutation-positive non-small cell lung cancer (NSCLC) who have progressed on epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy.
A partitioned survival model with three health states (progression-free, progressed disease, and death) from a UK payer perspective and over lifetime (15 years) was developed. Direct costs included disease management, treatment-related (acquisition, administration, monitoring, adverse events), and T790M testing costs. Efficacy and safety data were taken from clinical trials AURA extension and AURA2 for osimertinib and IMPRESS for PDC. An adjusted indirect treatment comparison was applied to reduce the potential bias in the non-randomized comparison. Parametric functions were utilized to extrapolate survival beyond the observed period. Health state utility values were calculated from EQ-5D data collected in the trials and valued using UK tariffs. Resource use and costs were based on published sources.
Osimertinib was associated with a gain of 1.541 quality-adjusted life-years (QALYs) at an incremental cost of £64,283 vs PDC (incremental cost-effectiveness ratio [ICER]: £41,705/QALY gained). Scenario analyses showed that none of the plausible scenarios produced an ICER above £44,000 per QALY gained, and probabilistic sensitivity analyses demonstrated a 63.4% probability that osimertinib will be cost-effective at a willingness-to-pay threshold of £50,000.
The analysis is subject to some level of uncertainty inherent to phase 2 single-arm data and the immaturity of the currently available survival data for osimertinib.
Osimertinib may be considered a cost-effective treatment option compared with PDC in the second-line setting in patients with EGFR-T790M mutation-positive NSCLC from a UK payer perspective. Further data from the ongoing AURA clinical trial program will reduce the inherent uncertainty in the analysis.
本研究进行了成本效用分析，旨在为英国国家卫生与临床优化研究所（NICE）对奥希替尼与铂类双联化疗（PDC）用于表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）治疗后进展的EGFR-T790M突变阳性非小细胞肺癌（NSCLC）患者的卫生技术评估提供参考。
从英国付费方的角度出发，建立了一个具有三种健康状态（无进展、疾病进展和死亡）的分区生存模型，时间跨度为终生（15年）。直接成本包括疾病管理、治疗相关（获取、给药、监测、不良事件）以及T790M检测成本。疗效和安全性数据取自奥希替尼的临床试验AURA扩展研究和AURA2以及PDC的IMPRESS研究。采用调整后的间接治疗比较来减少非随机比较中的潜在偏倚。利用参数函数外推观察期之外的生存情况。健康状态效用值根据试验中收集的EQ-5D数据计算得出，并使用英国关税进行估值。资源使用和成本基于已发表的资料。
与PDC相比，奥希替尼可带来1.541个质量调整生命年（QALY）的增益，增量成本为64,283英镑（增量成本效益比[ICER]：41,705英镑/QALY增益）。情景分析表明，在所有合理情景中，均未产生超过44,000英镑/QALY增益的ICER，概率敏感性分析显示，在支付意愿阈值为50,000英镑时，奥希替尼具有成本效益的概率为63.4%。
该分析受到2期单臂数据固有的一定程度的不确定性以及奥希替尼现有生存数据不成熟的影响。
从英国付费方的角度来看，在EGFR-T790M突变阳性NSCLC患者的二线治疗中，与PDC相比，奥希替尼可能被认为是一种具有成本效益的治疗选择。正在进行的AURA临床试验项目的进一步数据将减少分析中固有的不确定性。
