Wu Bin, Lu Shun
Medical Decision and Economic Group, Department of Pharmacy, Ren Ji Hospital, South Campus, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Shanghai Lung Cancer Center, Shanghai Chest Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China.
Transl Lung Cancer Res. 2020 Oct;9(5):1770-1784. doi: 10.21037/tlcr-19-605.
The effectiveness of adding pembrolizumab to chemotherapy improve outcomes in newly diagnosed metastatic non-small-cell lung cancer (NSCLC). We aimed to evaluate the economic outcomes of first-line treatment by adding pembrolizumab to chemotherapy with and without the use of PD-L1 testing for patient selection.
A decision-analytic model was adopted to project the disease course of newly diagnosed metastatic nonsquamous and squamous NSCLC without EGFR or ALK mutations. The efficacy and toxicity data were gathered from the KEYNOTE-189 and KEYNOTE-407 trials. Transition probabilities were estimated from the reported survival probabilities in each group. Cost and health preference data were derived from published economic evaluations. The incremental cost-effectiveness ratio (ICER) was measured, and subgroup, one-way and probabilistic sensitivity analyses (PSA) were performed for exploring the model uncertainties.
In the US context, pembrolizumab plus chemotherapy is projected to increase quality-adjusted-life year (QALY) by 1.168 and 0.988 in comparison with chemotherapy and the ICERs were $122,248 and $121,375/QALY in the whole nonsquamous and squamous patients with unconfirmed PD-L1 tumor proportion scores (TPS), respectively. After the selection of patients by PD-L1 TPS by PD-L1 testing, the ICERs of adding pembrolizumab treatment for patients with confirmed PD-L1 TPS >1% and ≥50% were $143,282 and $127,661/QALY in nonsquamous disease, and $131,495 and $121,554/QALY in squamous disease, respectively. The ICERs of adding pembrolizumab treatment for Chinese patients were higher than $40,000/QALY regardless of the histology and TPS subgroups, which highly exceed the willingness-to-pay threshold of $29,196/QALY (three times of per capita gross domestic product of China in 2018) in China.
Pembrolizumab plus chemotherapy as first-line treatment for untreated metastatic NSCLC without EGFR or ALK mutations is a cost-effective option regardless of PD-L1 expression status in the US context, and not cost-effective in the Chinese context. However, PD-L1 categories-directed pembrolizumab could not increase the cost-effectiveness of immunotherapy.
在新诊断的转移性非小细胞肺癌(NSCLC)中,帕博利珠单抗联合化疗可改善治疗效果。我们旨在评估在有和没有使用PD-L1检测进行患者选择的情况下,帕博利珠单抗联合化疗一线治疗的经济结果。
采用决策分析模型预测新诊断的无EGFR或ALK突变的转移性非鳞状和鳞状NSCLC的疾病进程。疗效和毒性数据来自KEYNOTE-189和KEYNOTE-407试验。转移概率根据每组报告的生存概率估算。成本和健康偏好数据来自已发表的经济评估。测量增量成本效益比(ICER),并进行亚组、单向和概率敏感性分析(PSA)以探索模型的不确定性。
在美国背景下,与化疗相比,帕博利珠单抗联合化疗预计可使质量调整生命年(QALY)分别增加1.168和0.988,在未确认PD-L1肿瘤比例评分(TPS)的全部非鳞状和鳞状患者中,ICER分别为122,248美元和121,375美元/QALY。通过PD-L1检测按PD-L1 TPS选择患者后,在非鳞状疾病中,为确认的PD-L1 TPS>1%和≥50%的患者添加帕博利珠单抗治疗的ICER分别为143,282美元和127,661美元/QALY,在鳞状疾病中分别为131,495美元和121,554美元/QALY。无论组织学和TPS亚组如何,为中国患者添加帕博利珠单抗治疗的ICER均高于40,000美元/QALY,这大大超过了中国29,196美元/QALY(2018年中国人均国内生产总值的三倍)的支付意愿阈值。
在美国背景下,帕博利珠单抗联合化疗作为未治疗的无EGFR或ALK突变的转移性NSCLC的一线治疗是一种具有成本效益的选择,而在中国背景下则不具有成本效益。然而,针对PD-L1类别使用帕博利珠单抗并不能提高免疫治疗的成本效益。