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Nivolumab Versus Docetaxel for Previously Treated Advanced Non-Small Cell Lung Cancer in China: A Cost-Effectiveness Analysis.

纳武利尤单抗与多西他赛治疗中国既往治疗的晚期非小细胞肺癌: 成本-效果分析。

  • 影响因子:2.04
  • DOI:10.1007/s40261-019-00869-3
  • 作者列表:"Liu Q","Luo X","Peng L","Yi L","Wan X","Zeng X","Tan C
  • 发表时间:2020-02-01

BACKGROUND AND OBJECTIVE:The economic assessment of immuno-oncology agents in Chinese patients is limited despite a need for new therapies. Nivolumab is the first immune checkpoint inhibitor approved for the second-line treatment of non-small cell lung cancer (NSCLC) in China, and it significantly prolongs overall survival. However, considering the high cost of nivolumab, it is urgent to assess its value in China in terms of both efficacy and cost. The objective of this study was to investigate the cost-effectiveness of nivolumab vs docetaxel in the second-line setting for NSCLC patients from the Chinese healthcare system perspective. METHODS:A Markov model consisting of three health states, was designed to evaluate the lifetime cost and effectiveness of nivolumab vs docetaxel in the second-line treatment of NSCLC patients. Clinical data was derived from the CheckMate 078 phase III clinical trial, which included 504 patients predominantly from China. Parametric survival models to fit and extrapolate survival data were chosen based on clinical rationality, visual fit and statistical goodness-of-fit. Lifetime costs and health outcomes were calculated, and US$28,899 and $63,564 per quality-adjusted life-year (QALY) were selected as the willingness-to-pay (WTP) threshold values for general regions and affluent regions, respectively. One-way and probabilistic sensitivity analyses were undertaken to explore the robustness of the model. Additional subgroup analyses were performed. RESULTS:In base case analysis, Nivolumab yielded an additional 0.24 QALYs, at a cost of $93,307 per QALY. Sensitivity analyses suggested that the results to be most sensitive to the price of nivolumab per kg (mean $60.00; range $26.00-$60.00) and the mean patient weight (65 kg, range 52-78 kg). Utility values in progression-free survival state (mean 0.804; range 0.643-0.965) and overall survival hazard ratio (0.68; 97.7% CI 0.52-0.90) had moderate impact on the model results. Subgroup analyses indicated that nivolumab was most cost-effective for patients who were 65 years of age or older ($85,171/QALY), followed by female patients ($85,273/QALY) and patients with tumor PD-L1 expression at least 1% ($90,309/QALY). CONCLUSIONS:Nivolumab is unlikely to be cost-effective compared with docetaxel for patients with previously treated advanced NSCLC in China. Ensuring that nivolumab is included in the National Reimbursement Drug List (NRDL) may be a valid mean of meeting extensive treatment demands in China.


背景和目的: 尽管需要新的治疗方法,但对中国患者免疫肿瘤药物的经济学评估是有限的。纳武利尤单抗是国内首个获批用于非小细胞肺癌 (NSCLC) 二线治疗的免疫检查点抑制剂,显著延长总生存期。然而,考虑到纳武利尤单抗的高成本,从疗效和成本两方面评估其在中国的价值迫在眉睫。本研究的目的是从中国医疗系统的角度调查纳武利尤单抗与多西他赛在二线治疗NSCLC患者中的成本效益。 方法: 设计了由三种健康状态组成的Markov模型,以评估纳武利尤单抗与多西他赛在NSCLC患者二线治疗中的终生成本和有效性。临床数据来源于CheckMate 078 III期临床试验,该试验包括 504 例主要来自中国的患者。基于临床合理性、视觉拟合和统计拟合优度选择用于拟合和外推生存数据的参数生存模型。计算终生成本和健康结果,选择每质量调整生命年 (QALY) 28,899 美元和 63,564 美元作为支付意愿 (WTP) 阈值分别为一般地区和富裕地区。进行了单向和概率敏感性分析,以探索模型的稳健性。进行了额外的亚组分析。 结果: 在基本病例分析中,Nivolumab产生了额外的 0.24 个QALY,每个QALY的成本为 93,307 美元。敏感性分析表明,结果对每公斤纳武利尤单抗的价格 (平均 60.00 美元; 范围 26.00-60.00 美元) 和平均患者体重 (65千克,范围 52-78千克)。无进展生存状态 (平均 0.804; 范围 0.643-0.965) 和总生存风险比 (0.68; 97.7% CI 0.52-0.90) 中的效用值对模型结果具有中等影响。亚组分析表明,纳武利尤单抗对 65 岁或以上的患者最具成本效益 ($85,171/QALY),其次是女性患者 ($85,273/QALY) 和患者肿瘤PD-L1 表达至少 1% ($90,309/QALY)。 结论: 与多西他赛相比,纳武利尤单抗治疗中国既往治疗的晚期NSCLC患者不太可能具有成本效益。确保纳武利尤单抗被纳入国家报销药物目录 (NRDL) 可能是满足中国广泛治疗需求的有效手段。



作者列表:["Mammana M","Zuin A","Serra E","Bellini A","Rea F"]

METHODS::Pulmonary artery sling is a rare congenital anomaly of the origin and course of the left pulmonary artery. Patients with this condition typically present with respiratory failure in young infancy, and asymptomatic cases are uncommon. We describe the case of an adult patient with a lung adenocarcinoma of the right upper lobe, extending into the hilum and superior mediastinum, and with a previously unknown pulmonary artery sling anomaly. The local invasiveness of the tumor and the peculiar vascular anatomy contributed to a unique surgical scenario, wherein multiple reconstructive procedures were required.

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作者列表:["Hata A","Nakajima T","Matsusaka K","Fukuyo M","Morimoto J","Yamamoto T","Sakairi Y","Rahmutulla B","Ota S","Wada H","Suzuki H","Matsubara H","Yoshino I","Kaneda A"]

METHODS::Patients with idiopathic pulmonary fibrosis (IPF) have higher risk of developing lung cancer, for example, squamous cell carcinoma (SCC), and show poor prognosis, while the molecular basis has not been fully investigated. Here we conducted DNA methylome analysis of lung SCC using 20 SCC samples with/without IPF, and noncancerous lung tissue samples from smokers/nonsmokers, using Infinium HumanMethylation 450K array. SCC was clustered into low- and high-methylation epigenotypes by hierarchical clustering analysis. Genes hypermethylated in SCC significantly included genes targeted by polycomb repressive complex in embryonic stem cells, and genes associated with Gene Ontology terms, for example, "transcription" and "cell adhesion," while genes hypermethylated specifically in high-methylation subgroup significantly included genes associated with "negative regulation of growth." Low-methylation subgroup significantly correlated with IPF (78%, vs. 17% in high-methylation subgroup, p = 0.04), and the correlation was validated by additional Infinium analysis of SCC samples (n = 44 in total), and data from The Cancer Genome Atlas (n = 390). The correlation between low-methylation subgroup and IPF was further validated by quantitative methylation analysis of marker genes commonly hypermethylated in SCC (HOXA2, HOXA9 and PCDHGB6), and markers specifically hypermethylated in high-methylation subgroup (DLEC1, CFTR, MT1M, CRIP3 and ALDH7A1) in 77 SCC cases using pyrosequencing (p = 0.003). Furthermore, low-methylation epigenotype significantly correlated with poorer prognosis among all SCC patients, or among patients without IPF. Multivariate analysis showed that low-methylation epigenotype is an independent predictor of poor prognosis. These may suggest that lung SCC could be stratified into molecular subtypes with distinct prognosis, and low-methylation lung SCC that significantly correlates with IPF shows unfavorable outcome.

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作者列表:["Zhang L","Yang Y","Chai L","Bu H","Yang Y","Huang H","Ran J","Zhu Y","Li L","Chen F","Li W"]

METHODS::The role of Fyn-related kinase (FRK) in malignant tumors remains controversial. Our study investigated the function of FRK in lung cancer. Immunohistochemistry staining and generating a knockout of FRK by CRISPR/Cas9 in H1299 (FRK-KO-H1299) cells were strategies used to explore the role of FRK. Immunohistochemistry staining indicated that FRK expression was elevated in 223 lung cancer tissues compared to 26 distant normal lung tissues. FRK contributed to poor survival status in lung cancer patients and acted as a predictor for poor prognosis of lung cancer. Knockout of FRK by CRISPR/Cas9 markedly inhibited proliferation, invasion, colony formation and epithelial-mesenchymal transition (EMT) process in the lung cancer cell line H1299. Further exploration indicated that FRK-KO damaged the stemness phenotype of H1299 by inhibiting CD44 and CD133 expression. Seahorse detection and a U-13 C flux assay revealed that FRK-KO induced metabolism reprogramming by inhibiting the Warburg effect and changing the energy type in H1299 cells. Epidermal growth factor stimulation recovered the expression of FRK and biological functions, metabolic reprogramming and stemness phenotype of H1299 cells. FRK plays an oncogenic role in lung cancer cells via a novel regulation mechanism of enhancing the stemness of H1299 cells by inducing metabolism reprogramming, which finally promotes EMT and metastasis. Our study also indicates that FRK could be used as a potential therapeutic target for drug development.

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