School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
Department of Clinical Oncology, Hospital Authority, Queen Elizabeth Hospital, Hong Kong SAR, China.
PLoS One. 2021 Mar 1;16(3):e0247860. doi: 10.1371/journal.pone.0247860. eCollection 2021.
Tyrosine kinase inhibitors (TKIs) therapy targets at epidermal growth factor receptor (EGFR) gene mutations in non-small-cell lung cancer (NSCLC). We aimed to compare the EGFR mutation-guided target therapy versus empirical chemotherapy for first-line treatment of advanced NSCLC in the public healthcare setting of Hong Kong.
A Markov model was designed to simulate outcomes of a hypothetical cohort of advanced (stage IIIB/IV) NSCLC adult patients with un-tested EGFR-sensitizing mutation status. Four treatment strategies were evaluated: Empirical first-line chemotherapy with cisplatin-pemetrexed (empirical chemotherapy group), and EGFR mutation-guided use of a TKI (afatinib, erlotinib, and gefitinib). Model outcome measures were direct medical cost, progression-free survival, overall survival, and quality-adjusted life-years (QALYs). Incremental cost per QALY gained (ICER) was estimated. Sensitivity analyses were performed to examine robustness of model results.
Empirical chemotherapy and EGFR mutation-guided gefitinib gained lower QALYs at higher costs than the erlotinib group. Comparing with EGFR mutation-guided erlotinib, the afatinib strategy gained additional QALYs with ICER (540,633 USD/QALY). In 10,000 Monte Carlo simulations for probabilistic sensitivity analysis, EGFR mutation-guided afatinib, erlotinib, gefitinib and empirical chemotherapy were preferred strategy in 0%, 98%, 0% and 2% of time at willingness-to-pay (WTP) 47,812 USD/QALY (1x gross domestic product (GDP) per capita), and in 30%, 68%, 2% and 0% of time at WTP 143,436 USD/QALY (3x GDP per capita), respectively.
EGFR mutation-guided erlotinib appears to be the cost-effective strategy from the perspective of Hong Kong public healthcare provider over a broad range of WTP.
酪氨酸激酶抑制剂（TKI）的治疗靶点是表皮生长因子受体（EGFR）基因在非小细胞肺癌（NSCLC）中的突变。我们旨在比较 EGFR 突变指导的靶向治疗与经验性化疗在香港公共医疗保健环境下对晚期 NSCLC 的一线治疗。
设计了一个马尔可夫模型来模拟一组未经测试的 EGFR 敏感突变状态的晚期（IIIb/IV 期）NSCLC 成年患者的假设队列的结果。评估了四种治疗策略：经验性一线化疗顺铂-培美曲塞（经验性化疗组）和 EGFR 突变指导的 TKI（阿法替尼、厄洛替尼和吉非替尼）的使用。模型结果指标为直接医疗成本、无进展生存期、总生存期和质量调整生命年（QALY）。估计增量成本每获得一个 QALY（ICER）。进行敏感性分析以检查模型结果的稳健性。
经验性化疗和 EGFR 突变指导的吉非替尼在花费更高的情况下获得的 QALYs 低于厄洛替尼组。与 EGFR 突变指导的厄洛替尼相比，阿法替尼策略的 ICER（540,633 美元/QALY）获得了额外的 QALYs。在 10,000 次蒙特卡罗模拟的概率敏感性分析中，在支付意愿（WTP）为 47,812 美元/QALY（1x 人均国内生产总值（GDP））时，EGFR 突变指导的阿法替尼、厄洛替尼、吉非替尼和经验性化疗在 0%、98%、0%和 2%的时间内成为首选策略，在 WTP 为 143,436 美元/QALY（3x GDP 人均）时，分别在 30%、68%、2%和 0%的时间内成为首选策略。
从香港公共医疗保健提供者的角度来看，EGFR 突变指导的厄洛替尼在广泛的 WTP 范围内似乎是一种具有成本效益的策略。
