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

• Published in: Journal of medical economics 2022-12, Vol.25 (1), p.469-480
• Main Authors: Aguiar-Ibáñez, Raquel, Hardern, Chloë, van Hees, Frank, Lee, Dawn, Patel, Anubhav, Chhabra, Nitika, Baluni, Gargi, Amonkar, Mayur, Lai, Yizhen, Xu, Ruifeng, Massaad, Rachid, Fogelman, David
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal, Humanized; colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Cost-Benefit Analysis; cost-effectiveness; deficient mismatch repair; DNA Mismatch Repair; economic analysis; Humans; Microsatellite instability; pembrolizumab; QALY; United States
• ISSN: 1369-6998; 1941-837X
• DOI: 10.1080/13696998.2022.2043634

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. 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. 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. 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 progressi