Cost-effectiveness of pembrolizumab for previously treated MSI-H/dMMR solid tumours in the UK

Patients with previously treated microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) tumours have limited chemotherapeutic treatment options. Pembrolizumab received approval from the EMA in 2022 for the treatment of colorectal, endometrial, gastric, small intestine, and biliary MSI-H/dMMR tumour types. This approval was supported by data from the KEYNOTE-164 and KEYNOTE-158 clinical trials. This study evaluated the cost-effectiveness of pembrolizumab compared with standard of care (SoC) for previously treated MSI-H/dMMR solid tumours in line with the approved EMA label from a UK healthcare payer perspective. A multi-tumour partitioned survival model was built consisting of pre-progression, progressed disease, and dead health states. Pembrolizumab survival outcomes were extrapolated using Bayesian hierarchical models (BHMs) fitted to pooled data from KEYNOTE-164 and KEYNOTE-158. Comparator outcomes were informed by published sources. Tumour sites were modelled independently and then combined, weighted by tumour site distribution. A SoC comparator was used to formulate the overall cost-effectiveness result with pembrolizumab as the intervention. SoC comprised a weighted average of the comparators by tumour site based on market share. Drug acquisition, administration, adverse events, monitoring, subsequent treatment, end-of-life costs, and testing costs were included. Sensitivity and scenario analyses were performed, including modelling pembrolizumab efficacy using standard parametric survival models. Pembrolizumab, at list price, was associated with £129,469 in total costs, 8.30 LYs, and 3.88 QALYs across the pooled tumour sites. SoC was associated with £28,222 in total costs, 1.14 LYs, and 0.72 QALYs across the pooled tumour sites. This yields an incremental cost-effectiveness ratio (ICER) of £32,085 per QALY. Results were robust to sensitivity and scenario analyses. This model demonstrates pembrolizumab provides a valuable new alternative therapy for UK patients with MSH-H/dMMR cancer at the cost of £32,085 per QALY, with confidential discounts anticipated to improve cost-effectiveness further.

既往接受过治疗的微卫星高度不稳定（microsatellite instability-high, MSI-H）/错配修复缺陷（mismatch repair deficient, dMMR）肿瘤患者，其化疗可选方案十分有限。帕博利珠单抗（Pembrolizumab）于2022年获欧洲药品管理局（EMA）批准，用于治疗结直肠癌、子宫内膜癌、胃癌、小肠癌及胆道癌的MSI-H/dMMR肿瘤亚型。此项获批得到了KEYNOTE-164与KEYNOTE-158两项临床试验数据的支持。本研究从英国医疗支付方视角出发，结合EMA获批的适应症标签，评估了帕博利珠单抗对比标准治疗（SoC）用于既往经治MSI-H/dMMR实体瘤的成本效果。研究构建了包含进展前、疾病进展及死亡三种健康状态的多肿瘤分区生存模型。利用拟合KEYNOTE-164与KEYNOTE-158合并数据的贝叶斯分层模型（BHMs）外推帕博利珠单抗的生存结局，对照干预的结局则基于已发表文献来源确定。研究对不同肿瘤部位分别建模后进行合并，权重由各肿瘤部位的分布比例决定。以标准治疗作为对照干预、帕博利珠单抗作为试验干预，计算整体成本效果结果；标准治疗为基于市场份额按肿瘤部位加权的各对照干预的平均方案。研究纳入了药品采购、给药、不良事件、监测、后续治疗、临终关怀成本及检测成本。本研究开展了敏感性分析与场景分析，包括采用标准参数生存模型对帕博利珠单抗的疗效进行建模。按挂牌价计算，帕博利珠单抗在合并肿瘤队列中的总成本为129469英镑，对应8.30个生命年（LYs）与3.88个质量调整生命年（QALYs）；标准治疗的总成本为28222英镑，对应1.14个生命年与0.72个质量调整生命年。据此计算得到增量成本效果比（ICER）为32085英镑每质量调整生命年。敏感性分析与场景分析结果均显示该结论稳健可靠。本模型证实，以32085英镑每质量调整生命年的成本，帕博利珠单抗可为英国MSI-H/dMMR癌症患者提供极具价值的新型治疗选择，而预计的保密折扣将进一步提升其成本效果。