基于分区生存模型的帕博利珠单抗单药与化疗一线治疗PD-L1肿瘤比例分数不同的非小细胞肺癌的成本-效果分析

目的：从卫生体系角度出发,评价帕博利珠单抗单药与化疗一线治疗PD-L1肿瘤比例分数≥1%的局部晚期或转移性非小细胞肺癌的经济性,为相关卫生决策提供参考。方法：根据疾病发展进程建立无进展、进展和死亡三状态分区生存模型,以质量调整生命年（QALY）作为产出指标计算增量成本-效果比。生存分析数据来自于一项多中心随机对照非盲的Ⅲ期临床试验KEYNOTE-042,成本数据来自于米内网和8个省市的医疗卫生服务项目价格中位数,效用数据源于已发表文献,并对关键参数进行敏感性分析和情景分析。结果：基础分析结果表明,相较于标准化疗组,帕博利珠单抗单药治疗相对于化疗的增量成本效果比在PD-L1肿瘤比例分数不同的人群中分别为228 254.12元/QALY（TPS≥50%）、351 267.03元/QALY（TPS≥20%）和256 990.96元/QALY（TPS≥1%）。单因素敏感性分析显示帕博利珠单抗价格和PFS状态效用等对ICER的变化有较大影响。概率敏感度分析结果表明模型结构稳定,稳健性较好。结论：在中国3倍人均GDP（193 932.00元）的意愿支付阈值下,帕博利珠单抗单药治疗与化疗相比不具有成本-效果,其经济性未来可通过降低价格来实现。     

帕博利珠单抗单药与化疗二线治疗晚期或转移性食管癌的成本-效果分析

目的:从我国卫生服务体系角度出发,评价帕博利珠单抗单药与化疗二线治疗晚期或转移性食管癌的经济性,为临床用药及相关卫生决策提供参考.方法:建立无进展生存、疾病进展和死亡3种健康状态的分区生存模型,以3周为模型周期,模拟患者终身,利用KEYNOTE-181临床试验数据和已发表的文献数据计算增量成本-效果比(ICER),并对...     

卡瑞利珠单抗联合化疗对比安慰剂联合化疗一线治疗局部晚期或转移性食管鳞状细胞癌的成本效果分析

目的:从中国卫生服务体系的角度出发,评价卡瑞利珠单抗联合化疗与安慰剂联合化疗一线治疗局部晚期或转移性食管鳞状细胞癌的成本效果。方法:基于一项针对中国局部晚期或转移性食管鳞状细胞癌患者的Ⅲ期随机双盲对照临床试验来构建分区生存模型,模拟患者终身的质量调整生命年和增量成本效果比,并进行单因素敏感性分析和概率敏感性分析来检验模型的不确定性。结果:基础分析结果显示,卡瑞利珠单抗组患者比安慰剂组患者多获得0.162个QALYs的同时,多花费33383.57元,增量成本效果比值为205072.47元/QALY,小于3倍人均GDP;单因素敏感性分析显示对模型最敏感的三个因素分别是PFS效用状态、卡瑞利珠单抗成本和效用贴现率;概率敏感性分析显示,当意愿支付数值大于3倍人均GDP时,卡瑞利珠单抗对比化疗方案为更具成本效果的概率为88.6%。结论:从中国卫生服务体系的角度来看,卡瑞利珠单抗联合化疗对比安慰剂联合化疗一线治疗局部晚期或转移性食管鳞状细胞癌是一种有经济效益的选择。     

卡瑞利珠单抗联合化疗对比化疗在晚期鳞状非小细胞肺癌一线治疗中的成本效果分析

目的: 从中国卫生体系角度出发,评价卡瑞利珠单抗联合化疗对比传统化疗一线治疗晚期鳞状非小细胞肺癌的成本效果。方法: 采用分区生存模型,计算95％患者死亡时的治疗成本、生存质量调整年和增量成本效果比,并进行单因素敏感性分析、概率敏感性分析和情景分析以检验基础结果的不确定性。结果: 相对于化疗组,卡瑞利珠单抗联合化疗成本增加100 397.39元,同时多获得0.52个QALY,增量成本效果比为191 281.04元/QALY;单因素敏感性分析显示,卡瑞利珠单抗成本、PFS状态效用和PD状态效用对结果影响较大;概率敏感性分析显示卡瑞利珠单抗联合化疗更具有成本效果的概率为96.7%;情景分析显示,当进展后治疗方案发生变化时,卡瑞利珠单抗组增量成本效果比未发生较大的变动,卡瑞利珠单抗治疗鳞状非小细胞肺癌纳入医保降价使其经济性增加。结论: 从中国卫生体系角度看,在晚期鳞状非小细胞肺癌的一线治疗中使用卡瑞利珠单抗联合化疗相对于化疗更具有成本效果优势。     

Cost-effectiveness of pembrolizumab in combination with chemotherapy versus chemotherapy and pembrolizumab monotherapy in the first-line treatment of squamous non-small-cell lung cancer in the US

Objective: To describe the cost-effectiveness of pembrolizumab plus chemotherapy (carboplatin and paclitaxel or nab-paclitaxel; P?+?C) in metastatic, squamous, non-small-cell lung cancer (NSCLC) patients in the US.

Methods: A model comparing P?+?C versus C alone is developed utilizing partitioned survival analysis. Primary clinical efficacy, treatment utilization, health utility and safety data are derived from the KEYNOTE-407 trial and projected over 20?years. Costs for drugs and non-drug disease management are also incorporated. Additionally, the cost-effectiveness of P?+?C vs. pembrolizumab monotherapy (P) is evaluated via an indirect treatment comparison, for patient subgroups with PD-L1 Tumor Proportion Score (TPS)?≥?50% and 1–49%.

Results: Overall, P?+?C is projected to increase life expectancy by 1.95?years vs. C (3.86 versus 1.91). The resultant ICER is $86,293/QALY. In patients with PD-L1?≥?50%, 1–49% and <1 the corresponding incremental cost-effectiveness ratios (ICERs) are $99,777/QALY, $85,986/QALY and $87,507/QALY, respectively. Versus P, in the PD-L1?≥?50% subgroup, P?+?C appears cost saving; however, this result should be interpreted with caution as there is considerable uncertainty in the relative efficacy of these comparators.

Conclusions: Across all eligible patients, the addition of pembrolizumab to chemotherapy is projected to approximately double life expectancy, yielding an extension to a point not previously seen in metastatic squamous NSCLC. Overall, and within all relevant PD-L1 subgroups, use of P?+?C yields an ICER below $100,000/QALY, and can be a cost-effective first-line treatment for eligible metastatic squamous NSCLC patients for whom chemotherapy is currently administered. In the PD-L1?≥?50% subgroup, additional follow-up within trials of pembrolizumab plus chemotherapy and pembrolizumab monotherapy are needed to better define cost-effectiveness between these comparators.     

Cost-effectiveness analysis of axitinib through a probabilistic decision model

Introduction: The Oncology field is characterised by a steady increase in demand and a consistent launching of innovative and expensive products. Therefore, cost-effectiveness analysis can contribute as a significant decision-making tool by elucidating the most economically efficient ways to satisfy compelling health needs.

Areas covered: The scope of this study is to estimate the cost-effectiveness of axitinib versus sorafenib, for the second-line treatment of renal cell carcinoma. A literature review for evidence synthesis was performed and a probabilistic Markov Model was employed to simulate disease progression. This study will also assess Value of Information.

Expert opinion: Compared to sorafenib, axitinib resulted in an incremental cost of 87,936 euro per quality adjusted life year. The probability of axitinib to being cost-effective at the willingness-to-pay threshold of 60,000 euro was 13%, while the corresponding probability of being cost-effective at the highest recommended willingness-to-pay threshold of 100,000 euro was 69.9%. Uncertainty was primarily attributed to the price of the product, the utility values, the progression-free survival and to a lesser degree to the overall survival. Axitinib can be considered as a cost-effective therapeutic option for second-line treatment of renal cell carcinoma.     

阿昔替尼单药或联合帕博利珠单抗治疗舒尼替尼治疗失败的伴肝转移肾细胞癌的疗效及安全性分析

目的 研究阿昔替尼单药或联合帕博利珠单抗治疗舒尼替尼治疗失败的伴肝转移肾细胞癌的疗效及安全性.方法 选取2018年1月—2020年5月南京医科大学第二附属医院和南京医科大学第四附属医院收治的26例肾细胞癌患者为研究对象.对照组13例接受阿昔替尼单药口服治疗,观察组13例接受阿昔替尼口服联合帕博利珠单抗治疗,比较两组患者...     

卡瑞利珠单抗联合化疗方案治疗复发或转移性鼻咽癌的成本效果分析

目的 评价卡瑞利珠单抗联合化疗方案一线治疗复发或转移性鼻咽癌的经济性。方法 构建分区生存模型,模拟患者的质量调整生命年（QALY）和增量成本效果比（ICER）,并进行单因素敏感性分析、概率敏感性分析和情境分析来检验模型的不确定性。结果 基础分析结果显示,相较于传统安慰剂联合化疗方案,使用卡瑞利珠单抗联合化疗方案一线治疗复发或转移性鼻咽癌的 ICER为 91 570.87元/QALY,远低于我国 3倍人均 GDP;单因素敏感性分析显示对模型结果影响程度最大的3个因素分别是无进展生存状态（PFS）的效用值、卡瑞利珠单抗成本及疾病进展后成本;概率敏感性分析显示,当意愿支付值大于15万元,卡瑞利珠单抗对比安慰剂联合顺铂和吉西他滨（GP方案）更具经济性的概率为100%;情境分析验证了基础分析的稳健性。结论 在我国3倍人均GDP的意愿支付值下,使用卡瑞利珠单抗联合GP方案一线治疗复发或转移性鼻咽癌更具经济性。     

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...     

Tivozanib for the treatment of renal cell carcinoma

Introduction: Renal cell carcinoma (RCC) represents a heterogeneous group of cancers with distinct histological features, molecular alterations, prognosis, and response to therapy. Target agents directed against vascular endothelial growth factor and its receptor and mammalian target of rapamycin (mTOR) inhibitors have completely changed the landscape of RCC. However, the rate of complete response is still low, thus supporting the research of novel therapeutic agents.

Area covered: The authors describe the chemical features of tivozanib, its pharmacodynamic and pharmacokinetic properties, and the results obtained in human phase I–III clinical trials. Tivozanib received its first global approval in EU, Iceland, and Norway on 28 August 2017 for the first-line treatment of adult patients with advanced RCC and for adult patients who are VEGFR and mTOR inhibitor-naive following disease progression after one prior treatment with cytokines.

Expert opinion: The US Food and Drug Administration did not approve tivozanib due to the lack of a significant advantage in terms of survival compared to sorafenib. To date, the role of tivozanib in the pharmaceutical landscape of mRCC appears to be very limited. However, ongoing trials on the association between tivozanib and immunotherapy may represent a promising strategy to be assessed in future clinical trials.     

Axitinib for renal cell carcinoma

Background: The approval of sunitinib, sorafenib and temsirolimus has dramatically altered the management of renal cell carcinoma (RCC). Bevacizumab plus IFN may also be added to the therapeutic armamentarium. Axitinib (AG-013736) is an oral and selective tyrosine kinase inhibitor. Objective: Data supporting the development of axitinib for RCC are reviewed. Methods: Preclinical and clinical data available for axitinib for RCC are presented. Results: Axitinib inhibits VEGFR-1, VEGFR-2 and VEGFR-3 with picomolar potencies, and PDGFR-α, PDGFR-β and c-kit with nanomolar potencies. Phase II clinical trials of axitinib in pretreated RCC following sorafenib or cytokine treatment have demonstrated promising activity accompanied by a favorable toxicity profile. Further development of axitinib for RCC is warranted.     

卡瑞利珠单抗联合卡铂和培美曲塞一线治疗晚期非鳞状非小细胞肺癌患者的成本-效果分析

目的 在2020年新版医保目录执行后癌症免疫治疗类药品降价的背景下,从卫生体系的角度,研究获批一线治疗晚期非鳞状非小细胞肺癌适应证的卡瑞利珠单抗联合化疗药品(卡铂和培美曲塞)与化疗药品单独使用的成本-效果,评估降价后药品的经济性.方法 基于一项在中国患者人群内开展的临床试验(CameL),通过建立分区生存模型,评价卡瑞...     

肾细胞癌辅助治疗研究进展

肾细胞癌(renal cell carcinoma,RCC)是泌尿外科常见的恶性肿瘤之一.早期RCC的治疗以根治性切除为主,但仍有约20％的患者最终发生远处转移.对于具有转移、复发高风险的患者以及已失去根治性手术机会的患者来说,通过辅助治疗来提高总的生存率,延长无进展生存期,提高生活质量是十分有意义的.虽然RCC对放化疗不敏感,但免疫治疗以及各种新的靶向治疗药物和方法给RCC的治疗带来了更多的选择和希望.文中就RCC辅助治疗研究进展进行综述.     

索拉非尼治疗转移性肾细胞癌的疗效及安全性研究

目的 评价索拉非尼治疗转移性肾癌的疗效及安全性.方法 转移性肾癌40例患者,均给予甲基磺酸索拉非尼片治疗,初始剂量为800 mg/d,2次/d,连续给药21 d,停药7d,观察疗效和不良反应,以及免疫组织化学检测结果.结果 40例患者中未见完全缓解（CR）和部分缓解（PR）;疾病稳定（SD） 32例（80.0％）和疾病进展（PD）8例（20.0％）;消化系统不良反应发生28例（70.0％）;间隙连接蛋白32（ Cx32）在局限性肾癌中表达阳性率为30.5％,明显低于转移性肾癌组织的1.2％（x2=8.123,P＜0.01）,Cx32表达与临床分期呈负相关（r=-0.419,P＜0.05）;肾癌组织中血管内皮生长因子（VEGF）蛋白表达的阳性率75.5％,明显高于正常肾组织的18.5％ （x2 =8.723,P＜0.01）;VEGF在局限性肾癌阳性表达率72.0％与转移性肾癌的89.1％差异无统计学意义（x2=1.978,P＞0.05）.结论 索拉非尼对晚期肾癌病情控制有较好的效果,是治疗转移性肾癌的新选择.     

Lenvatinib for use in combination with everolimus for the treatment of patients with advanced renal cell carcinoma following one prior anti-angiogenic therapy

Introduction: In patients with mRCC options for second line therapies, following progression on anti-angiogenic agents, that demonstrate a survival advantage in clinical trials have been limited. Recently a number of agents have demonstrated efficacy in this setting. Here in we profile one such therapy, the combination of lenvatinib and everolimus, and discuss the expanded options for therapy available in this setting.

Areas covered: In this review, we discuss current algorithms for treatment of mRCC in both the first-line and second-line setting. We discuss the recent addition of cabozantinib and nivolumab, in the second line setting, to the market. Lenvatinib’s pharmacology, clinical efficacy and toxicity profile is discussed. A comprehensive literature review was performed using PUBMED.

Expert commentary: The current treatment algorithms for mRCC will likely see significant change in the coming years. The addition of immunotherapy to our treatment options in mRCC is of particular importance. Future trials examining the use of immunotherapy, both as monotherapy and in combination with VEGF targeted therapy, will likely be a dominant influence in the therapeutic landscape of mRCC. Progress in terms of the rapid expansion of available active therapies in mRCC needs to be balanced with current deficiencies in terms of predictive biomarkers.     

Safety of available treatment options for renal cell carcinoma

ABSTRACT

Introduction: For many years, cytokines (high-dose interleukin (IL)-2 and interferon (IFN)) have been the unique available treatment options for metastatic renal cell carcinoma (mRCC) and they provided durable but modest responses at the cost of significant toxicities. To date, targeted therapies have replaced cytokine therapy due to higher response rates and more favorable toxicity profiles. The major classes of targeted therapy for mRCC include tyrosine kinase inhibitors, monoclonal antibody against vascular endothelial grow factors and inhibitors of the mammalian target of rapamycin. Thanks to these new strategies, the prognosis for the mRCC is shifting toward a chronic disease and the new challenges are the adequate treatment of adverse events (AEs) and the care for quality of life, which is crucial. Emerging immunotherapies targeting the programmed death-1 (PD-1) receptor and the programmed death ligand-1 (PD-L1) ligand have shown promising results in both efficacy and safety profiles.

Areas covered: Safety data published on available treatment options for renal cell carcinoma RCC are reviewed.

Expert opinion: Various toxicities are associated with targeted agents; these toxicities are generally well tolerated but careful monitoring and appropriate management are needed to optimize the use of these strategies.