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Cost-effectiveness of pembrolizumab for the first-line treatment of patients with unresectable or metastatic MSI-H/dMMR colorectal cancer in the United States
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 p...
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Published in: | Journal of medical economics 2022-12, Vol.25 (1), p.469-480 |
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creator | 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 |
description | 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 |
doi_str_mv | 10.1080/13696998.2022.2043634 |
format | article |
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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 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.</description><identifier>ISSN: 1369-6998</identifier><identifier>EISSN: 1941-837X</identifier><identifier>DOI: 10.1080/13696998.2022.2043634</identifier><identifier>PMID: 35184650</identifier><language>eng</language><publisher>England: Taylor & Francis</publisher><subject>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</subject><ispartof>Journal of medical economics, 2022-12, Vol.25 (1), p.469-480</ispartof><rights>2022 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Published by Informa UK Limited, trading as Taylor & Francis Group. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c413t-2f4151678358d398a2b9e2462840ee9202900e80746d9b2a2409d166303715c33</citedby><cites>FETCH-LOGICAL-c413t-2f4151678358d398a2b9e2462840ee9202900e80746d9b2a2409d166303715c33</cites><orcidid>0000-0003-4027-8456 ; 0000-0003-4135-4211 ; 0000-0002-3839-6966</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.tandfonline.com/doi/pdf/10.1080/13696998.2022.2043634$$EPDF$$P50$$Ginformaworld$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.tandfonline.com/doi/full/10.1080/13696998.2022.2043634$$EHTML$$P50$$Ginformaworld$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,27501,27923,27924,59142,59143</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35184650$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Aguiar-Ibáñez, Raquel</creatorcontrib><creatorcontrib>Hardern, Chloë</creatorcontrib><creatorcontrib>van Hees, Frank</creatorcontrib><creatorcontrib>Lee, Dawn</creatorcontrib><creatorcontrib>Patel, Anubhav</creatorcontrib><creatorcontrib>Chhabra, Nitika</creatorcontrib><creatorcontrib>Baluni, Gargi</creatorcontrib><creatorcontrib>Amonkar, Mayur</creatorcontrib><creatorcontrib>Lai, Yizhen</creatorcontrib><creatorcontrib>Xu, Ruifeng</creatorcontrib><creatorcontrib>Massaad, Rachid</creatorcontrib><creatorcontrib>Fogelman, David</creatorcontrib><title>Cost-effectiveness of pembrolizumab for the first-line treatment of patients with unresectable or metastatic MSI-H/dMMR colorectal cancer in the United States</title><title>Journal of medical economics</title><addtitle>J Med Econ</addtitle><description>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 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.</description><subject>Antibodies, Monoclonal, Humanized</subject><subject>colorectal cancer</subject><subject>Colorectal Neoplasms - drug therapy</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Cost-Benefit Analysis</subject><subject>cost-effectiveness</subject><subject>deficient mismatch repair</subject><subject>DNA Mismatch Repair</subject><subject>economic analysis</subject><subject>Humans</subject><subject>Microsatellite instability</subject><subject>pembrolizumab</subject><subject>QALY</subject><subject>United States</subject><issn>1369-6998</issn><issn>1941-837X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>0YH</sourceid><recordid>eNp9kc1O3DAUhaOqVUGUR6DyspuA_-LYu1aj8iMxqlSKxM5ykmvhyrGntgOCh-FZ62GGLuvF9V185x7pnKY5IfiUYInPCBNKKCVPKaa0Ds4E4--aQ6I4aSXr797XvTLtFjpojnP-jetjjOCefGwOWEckFx0-bF5WMZcWrIWxuAcIkDOKFm1gHlL07nmZzYBsTKjcA7IuVdi7AKgkMGWGUF5pU1xdM3p05R4tIUGu58zgAVXlDMXkUpERrW-u2suzab3-icboY9pSHo0mjJCQC68mt8EVmNBNVUD-1Hywxmc43v9Hze3591-ry_b6x8XV6tt1O3LCSkstJx0RvWSdnJiShg4KKBdUcgygakoKY5C452JSAzWUYzURIRhmPelGxo6aL7u7mxT_LJCLnl0ewXsTIC5ZU8GIIIpQVdFuh44p5pzA6k1ys0lPmmC9bUe_taO37eh9O1X3eW-xDDNM_1RvXVTg6w5woQY-m8eY_KSLeapB2VQzclmz_3v8BT3jnxw</recordid><startdate>20221231</startdate><enddate>20221231</enddate><creator>Aguiar-Ibáñez, Raquel</creator><creator>Hardern, Chloë</creator><creator>van Hees, Frank</creator><creator>Lee, Dawn</creator><creator>Patel, Anubhav</creator><creator>Chhabra, Nitika</creator><creator>Baluni, Gargi</creator><creator>Amonkar, Mayur</creator><creator>Lai, Yizhen</creator><creator>Xu, Ruifeng</creator><creator>Massaad, Rachid</creator><creator>Fogelman, David</creator><general>Taylor & Francis</general><scope>0YH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-4027-8456</orcidid><orcidid>https://orcid.org/0000-0003-4135-4211</orcidid><orcidid>https://orcid.org/0000-0002-3839-6966</orcidid></search><sort><creationdate>20221231</creationdate><title>Cost-effectiveness of pembrolizumab for the first-line treatment of patients with unresectable or metastatic MSI-H/dMMR colorectal cancer in the United States</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c413t-2f4151678358d398a2b9e2462840ee9202900e80746d9b2a2409d166303715c33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Antibodies, Monoclonal, Humanized</topic><topic>colorectal cancer</topic><topic>Colorectal Neoplasms - drug therapy</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Cost-Benefit Analysis</topic><topic>cost-effectiveness</topic><topic>deficient mismatch repair</topic><topic>DNA Mismatch Repair</topic><topic>economic analysis</topic><topic>Humans</topic><topic>Microsatellite instability</topic><topic>pembrolizumab</topic><topic>QALY</topic><topic>United States</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Aguiar-Ibáñez, Raquel</creatorcontrib><creatorcontrib>Hardern, Chloë</creatorcontrib><creatorcontrib>van Hees, Frank</creatorcontrib><creatorcontrib>Lee, Dawn</creatorcontrib><creatorcontrib>Patel, Anubhav</creatorcontrib><creatorcontrib>Chhabra, Nitika</creatorcontrib><creatorcontrib>Baluni, Gargi</creatorcontrib><creatorcontrib>Amonkar, Mayur</creatorcontrib><creatorcontrib>Lai, Yizhen</creatorcontrib><creatorcontrib>Xu, Ruifeng</creatorcontrib><creatorcontrib>Massaad, Rachid</creatorcontrib><creatorcontrib>Fogelman, David</creatorcontrib><collection>Taylor & Francis Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of medical economics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Aguiar-Ibáñez, Raquel</au><au>Hardern, Chloë</au><au>van Hees, Frank</au><au>Lee, Dawn</au><au>Patel, Anubhav</au><au>Chhabra, Nitika</au><au>Baluni, Gargi</au><au>Amonkar, Mayur</au><au>Lai, Yizhen</au><au>Xu, Ruifeng</au><au>Massaad, Rachid</au><au>Fogelman, David</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cost-effectiveness of pembrolizumab for the first-line treatment of patients with unresectable or metastatic MSI-H/dMMR colorectal cancer in the United States</atitle><jtitle>Journal of medical economics</jtitle><addtitle>J Med Econ</addtitle><date>2022-12-31</date><risdate>2022</risdate><volume>25</volume><issue>1</issue><spage>469</spage><epage>480</epage><pages>469-480</pages><issn>1369-6998</issn><eissn>1941-837X</eissn><abstract>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 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.</abstract><cop>England</cop><pub>Taylor & Francis</pub><pmid>35184650</pmid><doi>10.1080/13696998.2022.2043634</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-4027-8456</orcidid><orcidid>https://orcid.org/0000-0003-4135-4211</orcidid><orcidid>https://orcid.org/0000-0002-3839-6966</orcidid><oa>free_for_read</oa></addata></record> |
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source | Taylor & Francis Open Access |
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 |
title | Cost-effectiveness of pembrolizumab for the first-line treatment of patients with unresectable or metastatic MSI-H/dMMR colorectal cancer in the United States |
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