Ting Jie, Tien Ho PharmD, Xiang Pin, Sugay Amanda, Abdel-Sattar Maher, Wilson Leslie
Department of Clinical Pharmacy, University of California, San Francisco, CA, USA.
Department of Clinical Pharmacy, University of California, San Francisco, CA, USA.
Value Health. 2015 Sep;18(6):774-82. doi: 10.1016/j.jval.2015.04.008. Epub 2015 Jun 22.
To determine the cost-effectiveness of tyrosine kinase inhibitors erlotinib or afatinib, or chemotherapy cisplatin-pemetrexed, for first-line treatment of advanced epithelial growth factor receptor mutation-positive non-small-cell lung cancer in the United States. We also assessed the expected benefit of further research to reduce uncertainty regarding which treatment is optimal.
We developed a Markov model to compare the cost-effectiveness of erlotinib, afatinib, and cisplatin-pemetrexed. Model transition and adverse-effect probabilities were from two published phase III trials: EURTAC (Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer) and LUX-Lung (Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma) 3. EURTAC survival estimates were corrected for patients entering the trial with more severe disease, compared with LUX-Lung 3. Health utilities and costs were from national estimates or the published literature. Inputs were modeled as distributions for probabilistic sensitivity analysis and expected value of perfect information (EVPI) analysis to estimate the expected benefit of reducing uncertainty regarding the decision of optimal treatment.
In the base case, both tyrosine kinase inhibitors were more cost-effective than cisplatin-pemetrexed. Erlotinib had an incremental cost-effectiveness ratio of $61,809/quality-adjusted life-year (QALY) compared with afatinib. The acceptability curve showed that erlotinib was the optimal treatment at a willingness-to-pay threshold of $100,000/QALY (10-year population EVPI = $85.9 million). At a willingness-to-pay threshold of $50,000/QALY to $70,000/QALY (EVPI = $211.5 million-$261.8 million), however, there was considerable uncertainty whether erlotinib or afatinib was the optimal treatment.
Our analysis suggests that erlotinib is the preferred first-line treatment for advanced epithelial growth factor receptor mutation-positive non-small-cell lung cancer. Further research comparing erlotinib and afatinib is potentially justified, although accurate data are needed on the required cost and sample size of the trial.
确定酪氨酸激酶抑制剂厄洛替尼或阿法替尼，或化疗药物顺铂-培美曲塞，用于美国晚期表皮生长因子受体突变阳性非小细胞肺癌一线治疗的成本效益。我们还评估了进一步研究以减少关于哪种治疗最佳的不确定性的预期效益。
我们开发了一个马尔可夫模型，以比较厄洛替尼、阿法替尼和顺铂-培美曲塞的成本效益。模型转换和不良反应概率来自两项已发表的III期试验：EURTAC（厄洛替尼与标准化疗作为欧洲晚期表皮生长因子受体突变阳性非小细胞肺癌患者的一线治疗）和LUX-Lung 3（阿法替尼与基于顺铂的化疗用于表皮生长因子受体突变阳性肺腺癌）。与LUX-Lung 3相比，EURTAC生存估计针对病情更严重的入组患者进行了校正。健康效用和成本来自国家估计或已发表的文献。将输入建模为分布，用于概率敏感性分析和完美信息期望值（EVPI）分析，以估计减少关于最佳治疗决策的不确定性的预期效益。
在基础病例中，两种酪氨酸激酶抑制剂均比顺铂-培美曲塞更具成本效益。与阿法替尼相比，厄洛替尼的增量成本效益比为61,809美元/质量调整生命年（QALY）。可接受性曲线显示，在支付意愿阈值为100,000美元/QALY时，厄洛替尼是最佳治疗方案（10年人群EVPI = 8590万美元）。然而，在支付意愿阈值为50,000美元/QALY至70,000美元/QALY（EVPI = 2.115亿美元至2.618亿美元）时，厄洛替尼或阿法替尼是否为最佳治疗方案存在相当大的不确定性。
我们的分析表明，厄洛替尼是晚期表皮生长因子受体突变阳性非小细胞肺癌的首选一线治疗药物。尽管需要关于试验所需成本和样本量的准确数据，但比较厄洛替尼和阿法替尼的进一步研究可能是合理的。
