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.

Keywords:

• Microsatellite instability
• mismatch repair deficient
• economic analysis
• cost-effectiveness
• pembrolizumab
• multi-tumour
• histology-independent

JEL CLASSIFICATION CODES:

• D61
• D6
• D
• H51
• H5
• H

Transparency

Declaration of funding

This study was supported by funding from Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Declaration of financial/other interests

KY, RX, and MA are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. GM and CSH are employees of MSD (UK) Ltd., London, UK. MMW and EB are employees of Lumanity, UK, which received consultancy fees from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA in connection with this study. KM was an employee of Lumanity, UK at the time of the study. TM is an employee of Lumanity, US, which received consultancy fees from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA in connection with this study. JM was an employee of MSD, Switzerland, at the time of the study. RAI is an employee of Merck Canada Inc., Kirkland, QC, Canada.

Author contributions

GM, KY, MMW, and TM contributed substantially to the concept and design of the economic evaluation, data analysis and interpretation, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. EB and KM contributed substantially to data analysis and interpretation, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. JM contributed substantially to the statistical analysis and interpretation of the data, and the critical revision of the manuscript for important intellectual content. RX, CSH, and MA contributed substantially to the interpretation of the data, and critical revision of the manuscript for important intellectual content. RA contributed substantially to the concept and design of the economic evaluation, and critical revision of the manuscript for important intellectual content.

Acknowledgements

The authors gratefully acknowledge the support of Jean Muller and Mitashri Chaudhuri of MSD for their support with statistical programming. Howard Thom kindly provided external validation and feedback on the proposed modelling approach and model structure. Gianluca Baio provided technical and methodological input to the design of the Bayesian hierarchical models that informed the cost-effectiveness analysis.

Research sponsor

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD).

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.