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

Abstract

Objectives 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. Methods 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. Results 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. Conclusions 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.