Cost-effectiveness of pembrolizumab for the first-line treatment of patients with unresectable or metastatic MSI-H/dMMR colorectal cancer in the United States

Abstract

Aims

Approximately, 4% of Stage IV colorectal cancers (CRC) are microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) tumors. Patients with metastatic MSI-H/dMMR CRC receiving conventional therapies experience lower response rates and tend to have worse overall survival compared with patients with microsatellite stable (MSS)/proficient mismatch repair (pMMR) CRC. Pembrolizumab received FDA approval in 2020 for first-line treatment of Stage IV MSI-H/dMMR CRC based on significantly longer progression-free survival versus standard of care (SoC, 5-fluorouracil-based therapy with or without bevacizumab or cetuximab). This study evaluated the cost-effectiveness of pembrolizumab vs. SoC as per KEYNOTE-177 and other first-line treatments for MSI-H/dMMR CRC from a US healthcare system perspective.

Methods

A three-health-state partitioned-survival model was built using progression-free and overall survival data from KEYNOTE-177 and a network meta-analysis. Utilities were derived from KEYNOTE-177 EQ-5D-3L data. Drug acquisition, administration, AE, surgery, monitoring, subsequent treatment, and terminal care costs were included. Sensitivity and scenario analyses were performed, including utilizing a state-transition model structure and adopting a societal perspective.

Results

Over a lifetime time horizon, pembrolizumab and SoC were associated with total QALYs of 4.85 and 3.23, and total costs of $381,735 and $370,465, respectively, resulting in an ICER of $6,984 per QALY. QALY gains were mainly driven by extended survival with pembrolizumab. Pembrolizumab incurred higher drug acquisition costs relative to SoC but was cost-saving in terms of drug administration, AE, monitoring, subsequent treatment, and terminal care. Pembrolizumab dominated FOLFOX + panitumumab, FOLFOXIRI, and FOLFOXIRI + bevacizumab, and presented ICERs of $35,220 and $276 against XELOX and XELOX + bevacizumab. Results were robust to sensitivity and scenario analyses.

Conclusion

Pembrolizumab is highly cost-effective for the first-line treatment of unresectable or metastatic MSI-H/dMMR CRC in the US at a willingness-to-pay threshold of $100,000/QALY.

Key messages

• Pembrolizumab is a highly cost-effective option for the first-line treatment of patients with unresectable or metastatic MSI-H/dMMR colorectal cancer in the United States at a willingness-to-pay threshold of $100,000. Compared with the current standard of care for these patients, pembrolizumab:

• Increases survival due to delaying and preventing progression;

• Increases QALYs due to longer survival, improvement in HRQoL in the progression-free health state, and fewer Grade 3+ adverse events;

• Reduces costs associated with administering treatment, managing adverse events, monitoring post-progression disease, providing subsequent treatment, and providing terminal care; and

• Reduces indirect health care costs when taking a societal perspective due to productivity gains from delaying and preventing progression and death, less frequent treatment administration and less frequent Grade 3+ adverse events.

Keywords:

• Microsatellite instability
• QALY
• cost-effectiveness
• deficient mismatch repair
• economic analysis
• colorectal cancer
• pembrolizumab

JEL CLASSIFICATION CODES:

• C60
• C6
• C
• D61
• D6
• D
• I10
• I1
• I

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

RAI is an employee of Merck Canada Inc., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

CH and DL are employees of BresMed Health Solutions Ltd, UK, which received consultancy fees from Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA in connection with this study.

FvH is an employee of BresMed Health Solutions Ltd, NL, which received consultancy fees from Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA in connection with this study.

AP, NC, and GB are employees of Complete Health Economics and Outcomes Research Solutions, which received consultancy fees from Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA in connection with this study.

MA, YL, RX, RM, and DF are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

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

Acknowledgement

The authors would like to thank Jake Horgan (BresMed Health Solutions Ltd, UK) for his editorial assistance, and Jestinah Chevure (MSD, Belgium), for her support with statistical analyses.