■肾细胞癌是最常见的肾癌类型,占所有肾脏恶性肿瘤的约85%。晚期肾细胞癌患者是国家健康与护理卓越研究所多项技术评估的重点。患者疾病进展的风险取决于许多预后风险因素;患者被分类为具有中等/低风险或有利的疾病进展风险。
■这项多技术评估的目标是评估lenvatinib和pembrolizumab的临床有效性和成本效益,以及美国国家卫生与护理卓越研究所发布的最终范围中列出的相关比较剂:舒尼替尼,帕唑帕尼,tivozanib,卡博替尼和纳武单抗联合伊匹单抗。
■评估小组进行了临床和经济系统评价,并评估了卫材提交的临床和成本效益证据,哈特菲尔德,赫特福德郡,英国(lenvatinib的制造商)和默克夏普和多姆,怀特豪斯车站,NJ,美国(pembrolizumab的制造商)。评估小组使用贝叶斯框架进行固定效应网络荟萃分析,以产生临床有效性的证据。由于数据稀疏,出现了收敛问题,随机效应网络荟萃分析结果不可用.评估小组没有建立从头的经济模型,而是修改了MerckSharp&Dohme提供的分区生存模型。
■评估组临床系统评价确定了一项相关的随机对照试验(CLEAR试验)。清晰的审判是一个很好的质量,第三阶段,多中心,开放标签试验提供了lenvatinib联合pembrolizumab与舒尼替尼相比的有效性和安全性的证据.所有三个风险组的评估组无进展生存网络荟萃分析结果不应用于推断任何治疗比较的统计学显著差异(或缺乏统计学显著差异),这是由于试验内比例风险违反或比例风险假设有效性的不确定性。中/低风险亚组的评估组总体生存网络荟萃分析结果表明,但没有统计学意义,与接受卡博替尼或纳武单抗联合ipilimumab治疗的患者相比,接受乐伐替尼联合派博利珠单抗治疗的患者的总生存期有所改善.由于审判内比例风险违反或比例风险假设有效性的不确定性,对于有利风险亚组和所有风险人群,评估组总体生存网络荟萃分析结果不应用于推断任何治疗比较的统计学显著性差异(或无统计学显著性差异).仅一项成本效益研究被纳入评估小组对成本效益证据的审查。这项研究仅限于所有风险人群,从美国医疗保健系统的角度出发,包括美国国家健康与护理卓越研究所不推荐的未经治疗的晚期肾细胞癌患者的比较。因此,资源使用和结果可推广到NHS的程度尚不清楚.评估组的成本效益来自修改后的分区生存模型,该模型侧重于中/低风险和有利风险子组。评估小组的成本效益结果,使用所有药物的标价生成,表明,对于有利风险亚组的所有比较,与NHS患者可用的所有其他治疗方法相比,乐伐替尼联合派博利珠单抗治疗的成本更高,获益更少.对于中/低风险亚组,与卡博替尼和纳武单抗联合ipilimumab治疗相比,乐伐替尼联合派博利珠单抗治疗成本更高,获益更多.
■Lenvatinib+pembrolizumab与舒尼替尼比较的高质量临床有效性证据可从CLEAR试验中获得。对于大多数评估组贝叶斯风险比网络荟萃分析比较,由于试验中违反比例风险或不确定比例风险假设的有效性,因此很难得出结论.然而,用于填充经济模型的数据(临床效果和成本效果)与NHS临床实践相关,可用于告知美国国家健康与护理卓越研究所的决策.评估小组的成本效益结果,使用所有药物的标价生成,显示lenvatinib联合pembrolizumab的成本效益低于所有其他治疗方案。
■本研究注册为PROSPEROCRD4202128587。
■该奖项由美国国家卫生与护理研究所(NIHR)证据综合计划(NIHR奖项参考:NIHR134985)资助,并在《卫生技术评估》中全文发表;卷。28号49.有关更多奖项信息,请参阅NIHR资助和奖励网站。
肾细胞癌是最常见的肾癌类型。有几种药物治疗选择可用于患有晚期或转移性疾病的NHS患者,治疗的选择取决于患者疾病进展的风险。一种新的药物组合,lenvatinib加pembrolizumab,可能很快就可以用于治疗NHS患者。这篇综述探讨了lenvatinib联合pembrolizumab治疗是否为NHS提供了物有所值。我们回顾了乐伐替尼联合派姆单抗治疗与其他NHS治疗方案的有效性。我们还估计了lenvatinib联合pembrolizumab治疗与目前的NHS治疗对疾病进展风险较高和较低的患者的成本和收益。与目前的NHS治疗相比,乐伐替尼联合派博利珠单抗治疗可能会增加疾病进展风险较高(即疾病恶化)的患者存活时间.然而,对于疾病进展风险较低的患者,现有证据有限,仅表明乐伐替尼联合派姆单抗治疗可延长患者病情稳定的时间.对于所有患者来说,与目前所有的NHS治疗方法相比,lenvatinib联合pembrolizumab治疗非常昂贵.与当前NHS治疗未经治疗的肾细胞癌相比,使用公布的价格(不包括向NHS提供的任何折扣),lenvatinib联合pembrolizumab治疗可能无法为NHS提供良好的物有所值.
UNASSIGNED: Renal cell carcinoma is the most common type of kidney cancer, comprising approximately 85% of all renal malignancies. Patients with advanced renal cell carcinoma are the focus of this National Institute for Health and Care Excellence multiple technology appraisal. A patient\'s risk of disease progression depends on a number of prognostic risk factors; patients are categorised as having intermediate/poor risk or favourable risk of disease progression.
UNASSIGNED: The objectives of this multiple technology appraisal were to appraise the clinical effectiveness and cost-effectiveness of lenvatinib plus pembrolizumab versus relevant comparators listed in the final scope issued by the National Institute for Health and Care Excellence: sunitinib, pazopanib, tivozanib, cabozantinib and nivolumab plus ipilimumab.
UNASSIGNED: The assessment group carried out clinical and economic systematic reviews and assessed the clinical and cost-effectiveness evidence submitted by Eisai, Hatfield, Hertfordshire, UK (the manufacturer of lenvatinib) and Merck Sharp & Dohme, Whitehouse Station, NJ, USA (the manufacturer of pembrolizumab). The assessment group carried out fixed-effects network meta-analyses using a Bayesian framework to generate evidence for clinical effectiveness. As convergence issues occurred due to sparse data, random-effects network meta-analysis results were unusable. The assessment group did not develop a de novo economic model, but instead modified the partitioned survival model provided by Merck Sharp & Dohme.
UNASSIGNED: The assessment group clinical systematic review identified one relevant randomised controlled trial (CLEAR trial). The CLEAR trial is a good-quality, phase III, multicentre, open-label trial that provided evidence for the efficacy and safety of lenvatinib plus pembrolizumab compared with sunitinib. The assessment group progression-free survival network meta-analysis results for all three risk groups should not be used to infer any statistically significant difference (or lack of statistically significant difference) for any of the treatment comparisons owing to within-trial proportional hazards violations or uncertainty regarding the validity of the proportional hazards assumption. The assessment group overall survival network meta-analysis results for the intermediate-/poor-risk subgroup suggested that there was a numerical, but not statistically significant, improvement in the overall survival for patients treated with lenvatinib plus pembrolizumab compared with patients treated with cabozantinib or nivolumab plus ipilimumab. Because of within-trial proportional hazards violations or uncertainty regarding the validity of the proportional hazards assumption, the assessment group overall survival network meta-analysis results for the favourable-risk subgroup and the all-risk population should not be used to infer any statistically significant difference (or lack of statistically significant difference) for any of the treatment comparisons. Only one cost-effectiveness study was included in the assessment group review of cost-effectiveness evidence. The study was limited to the all-risk population, undertaken from the perspective of the US healthcare system and included comparators that are not recommended by the National Institute for Health and Care Excellence for patients with untreated advanced renal cell carcinoma. Therefore, the extent to which resource use and results are generalisable to the NHS is unclear. The assessment group cost-effectiveness results from the modified partitioned survival model focused on the intermediate-/poor-risk and favourable-risk subgroups. The assessment group cost-effectiveness results, generated using list prices for all drugs, showed that, for all comparisons in the favourable-risk subgroup, treatment with lenvatinib plus pembrolizumab costs more and generated fewer benefits than all other treatments available to NHS patients. For the intermediate-/poor-risk subgroup, treatment with lenvatinib plus pembrolizumab costs more and generated more benefits than treatment with cabozantinib and nivolumab plus ipilimumab.
UNASSIGNED: Good-quality clinical effectiveness evidence for the comparison of lenvatinib plus pembrolizumab with sunitinib is available from the CLEAR trial. For most of the assessment group Bayesian hazard ratio network meta-analysis comparisons, it is difficult to reach conclusions due to within-trial proportional hazards violations or uncertainty regarding the validity of the proportional hazards assumption. However, the data (clinical effectiveness and cost-effectiveness) used to populate the economic model are relevant to NHS clinical practice and can be used to inform National Institute for Health and Care Excellence decision-making. The assessment group cost-effectiveness results, generated using list prices for all drugs, show that lenvatinib plus pembrolizumab is less cost-effective than all other treatment options.
UNASSIGNED: This study is registered as PROSPERO CRD4202128587.
UNASSIGNED: This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis Programme (NIHR award ref: NIHR134985) and is published in full in Health Technology Assessment; Vol. 28, No. 49. See the NIHR Funding and Awards website for further award information.
Renal cell carcinoma is the most common type of kidney cancer. Several drug treatment options are available for NHS patients with advanced or metastatic disease, and the choice of treatment varies depending on a patient’s risk of disease progression. A new drug combination, lenvatinib plus pembrolizumab, may soon become available to treat NHS patients. This review explored whether treatment with lenvatinib plus pembrolizumab offered value for money to the NHS. We reviewed the effectiveness of treatment with lenvatinib plus pembrolizumab versus other NHS treatment options. We also estimated the costs and benefits of treatment with lenvatinib plus pembrolizumab versus current NHS treatments for patients with higher and lower risks of disease progression. Compared with current NHS treatments, treatment with lenvatinib plus pembrolizumab may increase the time that people with a higher risk of disease progression (i.e. worsening disease) were alive. However, for patients with a lower risk of disease progression, the available evidence is limited and only shows that treatment with lenvatinib plus pembrolizumab may prolong the time that patients have a stable level of disease. For all patients, compared to all current NHS treatments, treatment with lenvatinib plus pembrolizumab is very expensive. Compared with current NHS treatments for untreated renal cell carcinoma, using published prices (which do not include any discounts that are offered to the NHS), treatment with lenvatinib plus pembrolizumab may not provide good value for money to the NHS.