奥希替尼一线治疗EGFR突变局部晚期或转移性非小细胞肺癌的成本效果分析

目的对比奥希替尼与标准表皮生长因子受体-酪氨酸激酶抑制剂(EGFR-TKIs,吉非替尼或厄洛替尼)一线治疗EGFR突变的局部晚期或转移性非小细胞肺癌(NSCLC)的成本效果。方法运用Markov模型,评价两种治疗策略下的总成本与总健康产出,总成本以元表示,总产出以质量调整生命年(QALYs)表示。根据FLAURA试验数据,以增量成本效果比(ICER)为评价指标,通过TreeAge pro软件进行成本效果分析,并进行敏感性分析。结果与标准EGFR-TKIs治疗相比,奥希替尼治疗提高了0.48 QALYs,额外增加成本为93628.73元,ICER为196852.40元·QALY^-1,低于意愿支付成本阈值(198018元·QALY^-1)。敏感性分析结果显示,状态间的转化概率和状态的效用值是对研究结果造成最大影响的参数,奥希替尼与标准EGFR-TKIs相比具有成本效果优势的概率为85.067%。结论奥希替尼作为EGFR突变的局部晚期或转移性NSCLC的一线治疗方案比标准EGFR-TKIs具有成本效果优势。     

奥希替尼一线治疗非小细胞肺癌药物经济学评价

摘要：目的:基于卫生服务体系的角度,评价奥希替尼相对于标准表皮生长因子受体-酪氨酸激酶抑制药（EGFR-TKI）吉非替尼或厄洛替尼一线治疗非小细胞肺癌（NSCLC）的经济性。方法:基于FLAURA临床试验数据建立Markov模型,以增量成本-效果比（ICER）为指标评价奥希替尼与标准EGFR-TKI（吉非替尼或厄洛替尼）的成本-效果。模型周期为1个月,基线分析时间跨度设为5年,折现率为5%。采用单因素敏感度分析和概率敏感度分析对结果的不确定性进行评价。结果:5年的模拟结果显示,与标准EGFR-TKI组相比,奥希替尼组多获得0.73质量调整生命年（QALYs）,成本增加了42.3万元。ICER为57.9万元/QALY,超过了3倍人均国内生产总值（GDP）;敏感度分析结果提示,贴现率和奥希替尼的费用对总成本影响最大,其他参数影响较小。结论:奥希替尼一线治疗能延长NSCLC患者的生命年,提高生命质量,但同时也增加医疗成本。根据WHO 3倍人均GDP的判断标准,使用奥希替尼不具有成本-效果优势。     

EGFR- TKIs类药物治疗晚期非小细胞肺癌的药物经济学评价

【摘要】目的：引入Markov模型评价埃克替尼、吉非替尼和厄洛替尼三种EGFR- TKIs类药物二线治疗晚期非小细胞肺癌(NSCLC)的经济性,指导临床合理用药。方法：建立埃克替尼、吉非替尼和厄洛替尼治疗晚期非小细胞肺癌的Markov模型,分别对三种药物治疗晚期非小细胞肺癌患者疾病稳定、疾病缓解、疾病进展和死亡的动态变化进行模拟,同时对成本和效用值进行敏感度分析,找出临床相对较优的治疗药物。结果：Markov模型成本-效用分析显示：3%的贴现率下埃克替尼治疗晚期非小细胞肺癌3年所需累积成本为375594.37元,累积效用为1.50个质量调整生命年;吉非替尼所需累积成本为531222.33元,累积效用为1.51个质量调整生命年;厄洛替尼所需累积成本为694611.22元,累积效用为1.51个质量调整生命年。敏感度分析显示各参数在设定的范围内变化不影响模型分析结论。结论：三种EGFR- TKIs类药物相比,埃克替尼的成本效用比(250396.25元/QALY)远远小于吉非替尼(351802.87元/QALY)和厄洛替尼(460007.43元/QALY),是优选方案。因此,应优先选择埃克替尼作为晚期非小细胞肺癌的治疗药物,从而获得更优的经济学效益,使有限的医疗资源利用最大化。     

达可替尼对比吉非替尼一线治疗表皮生长因子受体突变晚期非小细胞肺癌的成本-效果分析

目的:从我国卫生体系的角度出发,在新版医保目录实施的背景下,评估降价后的达可替尼对比吉非替尼一线治疗EGFR突变的NSCLC的经济性。方法:基于一项三期临床试验的数据构建Markov模型,以增量成本-效果比(ICER)为指标评价达可替尼对比吉非替尼的经济性,并对结果进行敏感性分析。结果:模型运行结果显示,达可替尼相比吉非替尼的ICER为12 976 3.86元/QALY,小于3倍的我国人均GDP,达可替尼具有成本-效果优势。敏感性分析结果显示,无进展状态的效用值和达可替尼的成本对结果的影响最大;在WTP为3倍的我国人均GDP时,达可替尼具有成本-效果优势的概率为83.04%。结论:加入医保目录降价后的达可替尼对比吉非替尼一线治疗EGFR突变的NSCLC更具有经济性。     

达可替尼对比吉非替尼一线治疗EGFR突变晚期或转移性非小细胞肺癌的成本效果分析

目的比较达可替尼和吉非替尼一线治疗中国表皮生长因子受体(EGFR)突变晚期或转移性非小细胞肺癌(NSCLC)的成本效果。方法建立无疾病进展、疾病进展和死亡三种健康状态的分区生存模型。基于ARCHER 1050临床试验获取转移概率和安全性数据,根据已发表文献获得健康效用值,从卫生服务体系角度只考虑直接医疗成本,包括药品费用、随访费用、支持治疗费用和不良反应治疗费用。采用单因素和概率敏感性分析观察模型稳定性。结果一线治疗EGFR突变晚期或转移性NSCLC,达可替尼相比吉非替尼增加了0.80质量调整生命年(QALYs),每例患者的费用增加350 916.6元,增量成本效果比为303 033.2元·QALYs-1,高于全国3倍人均GDP的支付意愿阈值,低于北京、上海等经济发达地区3倍人均GDP的支付意愿阈值。单因素敏感性分析和概率敏感性分析结果表明,模型中的参数在一定范围内变化并未对结果产生显著影响。结论达可替尼一线治疗EGFR突变晚期或转移性非小细胞肺癌,与吉非替尼相比在全国人群中不具有成本效果优势,但在北京、上海等经济发达地区具有成本效果优势。     

EGFR-TKIs治疗晚期非小细胞肺癌的成本-效果分析

目的：评价埃克替尼、吉非替尼和厄洛替尼三种EGFR-TKIs类药物治疗晚期非小细胞肺癌（NSCLC）的成本-效果。方法：效果数据来源于文献资料的Meta分析结果,成本指直接药品成本,运用传统决策分析的原理和方法,评价三种二线治疗方案的经济性。结果：埃克替尼、吉非替尼和厄洛替尼组的成本分别为143550.85元、200750.00元和260662.14元,有效率分别为27.27%、25.57%和20.66%,疾病控制率分别为74.09%、73.52%和70.56%。结论：埃克替尼作为二线药物治疗晚期NSCLC效果略优于吉非替尼和厄洛替尼,且具有绝对的成本效果优势。     

阿法替尼和吉非替尼一线治疗EGFR突变阳性非小细胞肺癌的成本效用分析

目的 从中国医疗保健支付者的角度,评价阿法替尼与吉非替尼在表皮生长因子受体（epidermal growth factor receptor,EGFR）突变阳性非小细胞肺癌一线治疗中的成本效用。方法 基于一项高质量、多中心的二期随机临床试验（LUNG7）,依据疾病发展进程建立三状态Markov模型（无进展生存状态、疾病进展状态、死亡状态）,模型各状态转移概率与不良反应发生率通过临床试验数据提取并计算,效用值取自研究文献中的中国人群效用值,直接医疗成本取自本地收费或相关文献。对总人群Markov模型进行为期10年的成本效用评估,并对模型分析结果的稳定性进行确定敏感性和概率敏感性分析。结果 在基础分析中,10年间阿法替尼组相对于吉非替尼组需多花费$16 499.77,但同时可多获得0.29个质量调整生命年（quality-adjusted life years,QALYs）,其增量成本效果比（incremental cost-effectiveness ratio,ICER）为$57 428.17/QALY。此时ICER值高于中国支付意愿阈值（willingness to pay,WTP）$26 331/QALY,表明阿法替尼目前相对于吉非替尼不具经济优势。一维敏感性分析结果显示疾病进展阶段的效用值、吉非替尼和阿法替尼的价格以及无进展生存期效用值对结果的稳定性影响较大,但除吉非替尼价格外,其他变量均不能使ICER值降至WTP之下,表明模型结果稳定。结论 对于中国EFGR突变阳性非小细胞肺癌患者,阿法替尼在一线治疗中相对于吉非替尼当前没有表现出经济性。     

EGFR-TKIs治疗晚期非小细胞肺癌效果的Meta分析

目的：根据临床研究文献,采用 Meta 分析法综合评价EGFR-TKIs类药物治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的临床疗效。方法：检索 CNKI、维普、万方、SCI、Pubmed、Science Direct等数据库中2005年至2013 年期间发表的有关EGFR-TKIs对比治疗晚期NSCLC的临床研究资料,采用 RevMan5.0和ITC软件,对入选的国内外10篇有关EGFR-TKIs对比治疗晚期NSCLC的研究文献进行综合定量分析。结果：Meta 分析结果显示,埃克替尼与吉非替尼治疗晚期NSCLC有效率和疾病控制率的RR值分别为1.07(P＝0.69)、1.01(P＝0.89);吉非替尼与厄洛替尼治疗晚期NSCLC有效率和疾病控制率的RR值分别为1.23(P＝0.10)、1.04(P＝0.46);埃克替尼与厄洛替尼治疗晚期NSCLC有效率和疾病控制率的RR值分别为1.32(P＝0.79)、1.05(P＝0.95)。结论：埃克替尼、吉非替尼和厄洛替尼治疗晚期NSCLC的效果无显著性差异,但三者的临床有效性尚需要更多高质量的临床随机对照研究来证实。     

埃克替尼治疗表皮生长因子受体突变型非小细胞肺癌患者49例

目的评价埃克替尼治疗表皮生长因子受体(EGFR)突变型非小细胞肺癌(NSCLC)患者的临床有效性及安全性。方法回顾性分析本院2011年12月—2013年12月年内住院的服用埃克替尼治疗的49例EGFR突变型NSCLC患者,以同期服用吉非替尼治疗的21例患者作为对照,比较两组的体能状态、生活质量评价及疗效和安全性评价。结果埃克替尼和吉非替尼组客观有效率分别为59%和57%,疾病控制率分别为84%和81%,两组相比无显著差异(P>0.05)。埃克替尼组在不良反应发生的类别、发生率及不良反应的分级等方面与吉非替尼组无显著差异(P>0.05)。结论埃克替尼治疗EGFR突变型NSCLC患者疗效确切、不良反应发生率较低,与吉非替尼相似。     

克唑替尼一线治疗ALK阳性非小细胞肺癌的成本-效果分析

摘要：目的:比较克唑替尼和培美曲塞联合顺铂一线治疗间变淋巴瘤激酶(ALK)阳性非小细胞肺癌(NSCLC)的成本-效果。方法:从医疗保健系统角度出发,构建三状态Markov模型模拟疾病病程,根据Ⅲ期临床试验数据获得各状态之间的转移概率,从已发表文献获得成本数据,效果指标为质量调整生命年(QALY);采用成本-效果分析法比较两方案的经济性,并进行敏感性分析。结果:克唑替尼组和培美曲塞联合顺铂化疗组的两年总成本分别为554 322.4元和293 622.8元,分别获得1.48QALYs和1.33 QALYs,克唑替尼组的收益较化疗组更高,但成本也高于化疗组,增量成本-效果比(ICER)为1 698 291元/QALY,高于支付意愿阈值161 805元(3倍人均GDP)。结论:短期分析结果提示,与培美曲塞联合顺铂化疗相比,克唑替尼治疗ALK阳性晚期NSCLC不具有经济性,克唑替尼组效用值为主要决定因素。     

Cost-effectiveness analysis of tyrosine kinase inhibitors (erlotinib,gefitinib, afatinib and osimertinib) as first-line therapy for epidermal growth factor receptor-mutated advanced non-small cell lung cancer

Gefitinib, erlotinib, afatinib and osimertinib have been recommended as the first-line treatment for epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC), whereas no studies have compared the cost-effectiveness of these four tyrosine kinase inhibitors (TKIs) simultaneously in China. In the present study, we aimed to estimate the cost-effectiveness of erlotinib, gefitinib, afatinib and osimertinib for untreated EGFR-mutated advanced NSCLC. A Markov model was constructed to compare the 10-year impact of four TKIs for patients with treatment-naive EGFR-mutated advanced NSCLC from the perspective of the Chinese medical system. Clinical data and utility values were derived from published literature, and costs were obtained from Chinese official websites. The primary output indicator was the incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed to test the robustness of the model. We found that afatinib was estimated to spend the lowest cost with minimum life-years (LYs), while osimertinib was the most expensive regimen with maximum LYs. The ICER of gefitinib versus afatinib was \$732/quality-adjusted life-year (QALY), which was less than the willingness-to-pay (WTP) of \$29 382/QALY. Compared with gefitinib, erlotinib yielded a higher cost and a shorter lifetime, hence it was identified as a dominated strategy. Then, osimertinib was compared to gefitinib, which produced an ICER of \$71 330/QALY, exceeding the WTP. It suggested that gefitinib was the most cost-effective regimen as the first-line treatment for EGFR-mutated advanced NSCLC. Decreasing the osimertinib price or increasing the WTP threshold to \$68 558/QALY might enhance the favorability of the outcome, by which osimertinib might become more cost-effective. One-way sensitivity analysis manifested that the model was robust.     

Safety of gefitinib in non-small cell lung cancer treatment

ABSTRACT

Introduction: The development of EGFR TKI and the subsequent identification of activating EGFR mutations have dramatically changed how NSCLC is treated. With its recent approval by the US Food and Drug Administration, gefitinib adds to the list of recommended first-line treatments for lung cancer harboring EGFR mutations, which hitherto includes erlotinib and afatinib.

Areas covered: This review summarizes the pharmacological property, clinical efficacy, and safety of gefitinib in major clinical trials and post-marketing studies.

Expert opinion: Gefitinib is a well-tolerated treatment for advanced NSCLC. The most common adverse events are skin reaction and diarrhea, both of which are generally mild, noncumulative, and manageable. Other side effects such as interstitial lung disease and liver toxicity are less common but can be serious. Which EGFR TKI is the preferred first-line treatment is a matter of debate. Gefitinib and erlotinib have comparable efficacy, whereas afatinib may exert superior clinical activity over gefitinib. In terms of the most common toxicities of skin reaction and diarrhea, gefitinib may be the most tolerable of the three. Hence, despite being the earliest EGFR TKI developed, gefitinib continues to be one of the first-line treatments for advanced EGFR-mutated NSCLC, especially when skin and gastrointestinal toxicity is a concern.     

Pharmacokinetic drug evaluation of osimertinib for the treatment of non-small cell lung cancer

Introduction: First- and second-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, erlotinib, icotinib, and afatinib are the standard-of-care for first-line therapy of non-small-cell lung cancer (NSCLC) harboring activating EGFR mutations. Unfortunately, after initial activity of an average 9–13 months, disease progression has been reported in the majority of patients. In about 50% of cases the progression is due to the onset of the T790M mutation in exon 20 of the EGFR gene. Third-generation EGFR-TKIs targeting this mutation were investigated, with osimertinib the only reaching clinical practice.

Areas covered: A structured search of bibliographic databases for peer-reviewed research literature and of main meetings using a focused review question addressing osimertinib, was undertaken.

Expert opinion: Osimertinib is the standard-of-care for EGFR-mutated patients progressing to first-line EGFR-TKIs due to the acquired EGFR T790M mutation. Results from the head-to-head first-line trial comparing osimertinib versus gefitinib or erlotinib in activating EGFR mutations might change the front-line approach. Osimertinib in combination regimens, such as immunotherapy, and in adjuvant setting are ongoing. Thus, the strategic approach for the management of EGFR-mutated NSCLC patients will change further in the next few years.     

阿替利珠单抗联合标准化疗方案治疗广泛期小细胞肺癌的成本-效用分析

目的:从卫生体系角度评价阿替利珠单抗联合标准化疗方案对比单用化疗方案一线治疗广泛期小细胞肺癌(ES-SCLC)的经济性。方法:参考一项Ⅲ期临床试验数据(IMpower133研究)及其他文献数据构建ES-SCLC患者分区生存模型,评价阿替利珠单抗联合标准化疗方案(依托泊苷+卡铂)对比单纯化疗方案(依托泊苷+卡铂)一线治疗ES-SCLC的经济性;并采用单因素敏感性分析和概率敏感性分析法评价结果的稳定性。结果:成本-效用分析结果显示,阿替利珠单抗联合化疗组的成本为489598.52元,效用为0.70质量调整生命年(QALYs);单纯化疗组的成本为126276.80元,效用为0.55 QALYs;两组相比的增量成本-效用比(ICUR)为2361709.05元/QALY,远超意愿支付阈值(WTP)(即2019年我国3倍人均GDP,212676元)。单因素敏感性分析结果显示,阿替利珠单抗联合化疗组无进展状态效用值对成本-效用分析结果的影响最大;概率敏感性分析结果提示,在0~500000元/QALY的WTP范围内,阿替利珠单抗联合化疗方案始终不具有经济性。结论:阿替利珠单抗联合化疗方案对比单用化疗方案治疗ES-SCLC在我国现有的经济水平下不具有成本-效用优势。     

Class act: safety comparison of approved tyrosine kinase inhibitors for non-small-cell lung carcinoma

Introduction: The past decade has seen the development and widespread use of tyrosine kinase inhibitors (TKIs) targeting a mutated EGFR (mEGFR) for the treatment of metastatic NSCLC. We discuss the main properties of the TKIs currently recommended for the treatment of mEGFR NSCLC: gefitinib, erlotinib and afatinib.

Areas covered: The mechanism of action, pharmacodynamics and pharmacokinetics of these drugs, with emphasis on the historical context of their preclinical and clinical development, will be covered, including potential resistance mechanisms to these first-generation TKIs that has driven the trial design for second and third generations of EGFR inhibitors. Six Phase III clinical trials comparing these three TKIs with cisplatin-based chemotherapy upfront for mEGFR NSCLC provide the basis for the comparative safety and toxicity analysis between these agents. Class-related toxicity of these EGFR inhibitors, including life-threatening effects, will be discussed.

Expert opinion: Toxicity and safety analysis from the Phase III trials of these agents in mEGFR populations suggests that afatinib has more frequent and severe side effects. Given that an efficacy advantage has not yet been demonstrated for afatinib over erlotinib and gefitinib, the consistent class toxicity profile of these agents means that gefitinib and erlotinib are a safer first-line treatment recommendation.     

基于Markov模型评价罗沙司他对比重组人促红素治疗非透析患者肾性贫血的经济学研究

目的：从医疗体系角度,比较罗沙司他与重组人促红素治疗非透析依赖性慢性肾病（NDD-CKD）患者贫血的经济性,为肾性贫血的治疗提供参考依据。方法：使用Markov模型评价罗沙司他与重组人促红素的成本与效用,得到患者的治疗成本和质量调整生命年（QALY）。临床参数来自DOLOMITES研究;相关成本和效用数据来自国内外文献。对成本-效用分析结果进行单因素敏感性分析和概率敏感性分析。结果：罗沙司他总治疗成本为44 940.33元,重组人促红素总治疗成本为18 732.60元,使用罗沙司他的患者可获得的QALY为9.51,使用重组人促红素的患者可获得的QALY为9.38,增量成本效果比（ICER）分析显示：ICER为201 597.92元/QALY,小于3倍人均GDP。因此,与重组人促红素相比,罗沙司他治疗NDD-CKD患者具有一定的成本-效用优势。结论：在中国目前的经济情况下,罗沙司他在治疗NDD-CKD患者贫血时具有一定的经济学优势。