Association of CD274 (PD-L1) Copy Number Changes with Immune Checkpoint Inhibitor Clinical Benefit in Non-Squamous Non-Small Cell Lung Cancer
We sought to characterize response to immune checkpoint inhibitor (ICI) in non-squamous non-small cell lung cancer (NSCLC) across various CD274 copy number gain and loss thresholds and identify an optimal cutoff. A de-identified nationwide (US) real-world clinico-genomic database was leveraged to st...
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| Veröffentlicht in: | The oncologist (Dayton, Ohio) Ohio), 2022-09, Vol.27 (9), p.732-739 |
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| creator | Murugesan, Karthikeyan Jin, Dexter X Comment, Leah A Fabrizio, David Hegde, Priti S Elvin, Julia A Alexander, Brian Levy, Mia A Frampton, Garrett M Montesion, Meagan Roychowdhury, Sameek Kurzrock, Razelle Ross, Jeffrey S Albacker, Lee A Huang, Richard S P |
| description | We sought to characterize response to immune checkpoint inhibitor (ICI) in non-squamous non-small cell lung cancer (NSCLC) across various CD274 copy number gain and loss thresholds and identify an optimal cutoff.
A de-identified nationwide (US) real-world clinico-genomic database was leveraged to study 621 non-squamous NSCLC patients treated with ICI. All patients received second-line ICI monotherapy and underwent comprehensive genomic profiling as part of routine clinical care. Overall survival (OS) from start of ICI, for CD274 copy number gain and loss cohorts across varying copy number thresholds, were assessed.
Among the 621 patients, patients with a CD274 CN greater than or equal to specimen ploidy +2 (N = 29) had a significantly higher median (m) OS when compared with the rest of the cohort (N = 592; 16.1 [8.9-37.3] vs 8.6 [7.1-10.9] months, hazard ratio (HR) = 0.6 [0.4-1.0], P-value = .05). Patients with a CD274 copy number less than specimen ploidy (N = 299) trended toward a lower mOS when compared to the rest of the cohort (N = 322; 7.5 [5.9-11.3] vs 9.6 [7.9-12.8] months, HR = 0.9 [0.7-1.1], P-value = .3).
This work shows that CD274 copy number gains at varying thresholds predict different response to ICI blockade in non-squamous NSCLC. Considering these data, prospective clinical trials should further validate these findings, specifically in the context of PD-L1 IHC test results. |
| doi_str_mv | 10.1093/oncolo/oyac096 |
| format | Article |
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A de-identified nationwide (US) real-world clinico-genomic database was leveraged to study 621 non-squamous NSCLC patients treated with ICI. All patients received second-line ICI monotherapy and underwent comprehensive genomic profiling as part of routine clinical care. Overall survival (OS) from start of ICI, for CD274 copy number gain and loss cohorts across varying copy number thresholds, were assessed.
Among the 621 patients, patients with a CD274 CN greater than or equal to specimen ploidy +2 (N = 29) had a significantly higher median (m) OS when compared with the rest of the cohort (N = 592; 16.1 [8.9-37.3] vs 8.6 [7.1-10.9] months, hazard ratio (HR) = 0.6 [0.4-1.0], P-value = .05). Patients with a CD274 copy number less than specimen ploidy (N = 299) trended toward a lower mOS when compared to the rest of the cohort (N = 322; 7.5 [5.9-11.3] vs 9.6 [7.9-12.8] months, HR = 0.9 [0.7-1.1], P-value = .3).
This work shows that CD274 copy number gains at varying thresholds predict different response to ICI blockade in non-squamous NSCLC. Considering these data, prospective clinical trials should further validate these findings, specifically in the context of PD-L1 IHC test results.</description><identifier>ISSN: 1083-7159</identifier><identifier>EISSN: 1549-490X</identifier><identifier>DOI: 10.1093/oncolo/oyac096</identifier><identifier>PMID: 35598202</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Cancer Diagnostics and Molecular Pathology ; Copy number variations ; Diagnosis ; Drug therapy ; Health aspects ; Influence ; Lung cancer, Non-small cell</subject><ispartof>The oncologist (Dayton, Ohio), 2022-09, Vol.27 (9), p.732-739</ispartof><rights>The Author(s) 2022. Published by Oxford University Press.</rights><rights>COPYRIGHT 2022 Oxford University Press</rights><rights>The Author(s) 2022. Published by Oxford University Press. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c417t-52f974fdf7a9cd1187a0a4155839ce08f9b4fc5dca293c4a166e5ae5e5b4f3a33</citedby><cites>FETCH-LOGICAL-c417t-52f974fdf7a9cd1187a0a4155839ce08f9b4fc5dca293c4a166e5ae5e5b4f3a33</cites><orcidid>0000-0001-8395-5168 ; 0000-0002-5070-1783 ; 0000-0002-2275-1126</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9438920/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9438920/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35598202$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Murugesan, Karthikeyan</creatorcontrib><creatorcontrib>Jin, Dexter X</creatorcontrib><creatorcontrib>Comment, Leah A</creatorcontrib><creatorcontrib>Fabrizio, David</creatorcontrib><creatorcontrib>Hegde, Priti S</creatorcontrib><creatorcontrib>Elvin, Julia A</creatorcontrib><creatorcontrib>Alexander, Brian</creatorcontrib><creatorcontrib>Levy, Mia A</creatorcontrib><creatorcontrib>Frampton, Garrett M</creatorcontrib><creatorcontrib>Montesion, Meagan</creatorcontrib><creatorcontrib>Roychowdhury, Sameek</creatorcontrib><creatorcontrib>Kurzrock, Razelle</creatorcontrib><creatorcontrib>Ross, Jeffrey S</creatorcontrib><creatorcontrib>Albacker, Lee A</creatorcontrib><creatorcontrib>Huang, Richard S P</creatorcontrib><title>Association of CD274 (PD-L1) Copy Number Changes with Immune Checkpoint Inhibitor Clinical Benefit in Non-Squamous Non-Small Cell Lung Cancer</title><title>The oncologist (Dayton, Ohio)</title><addtitle>Oncologist</addtitle><description>We sought to characterize response to immune checkpoint inhibitor (ICI) in non-squamous non-small cell lung cancer (NSCLC) across various CD274 copy number gain and loss thresholds and identify an optimal cutoff.
A de-identified nationwide (US) real-world clinico-genomic database was leveraged to study 621 non-squamous NSCLC patients treated with ICI. All patients received second-line ICI monotherapy and underwent comprehensive genomic profiling as part of routine clinical care. Overall survival (OS) from start of ICI, for CD274 copy number gain and loss cohorts across varying copy number thresholds, were assessed.
Among the 621 patients, patients with a CD274 CN greater than or equal to specimen ploidy +2 (N = 29) had a significantly higher median (m) OS when compared with the rest of the cohort (N = 592; 16.1 [8.9-37.3] vs 8.6 [7.1-10.9] months, hazard ratio (HR) = 0.6 [0.4-1.0], P-value = .05). Patients with a CD274 copy number less than specimen ploidy (N = 299) trended toward a lower mOS when compared to the rest of the cohort (N = 322; 7.5 [5.9-11.3] vs 9.6 [7.9-12.8] months, HR = 0.9 [0.7-1.1], P-value = .3).
This work shows that CD274 copy number gains at varying thresholds predict different response to ICI blockade in non-squamous NSCLC. Considering these data, prospective clinical trials should further validate these findings, specifically in the context of PD-L1 IHC test results.</description><subject>Cancer Diagnostics and Molecular Pathology</subject><subject>Copy number variations</subject><subject>Diagnosis</subject><subject>Drug therapy</subject><subject>Health aspects</subject><subject>Influence</subject><subject>Lung cancer, Non-small cell</subject><issn>1083-7159</issn><issn>1549-490X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNptkt9rFDEQxxdRbK2--igBX-rDtskm2WxehHPrj4OjCir4FuZyk7vobnLd7Cr3R_R_bo47i0IJJJPJZ77MhG9RvGT0glHNL2OwsYuXcQeW6vpRccqk0KXQ9MfjHNOGl4pJfVI8S-knpTnk1dPihEupm4pWp8XtLKVoPYw-BhIdaa8qJcj5l6tywd6QNm535HrqlziQdgNhjYn88eOGzPt-CphzaH9tow8jmYeNX_oxZrDzwVvoyDsM6PxIfCDXMZRfbybo45QOlx66jrSYt8UU1qSFYHF4Xjxx0CV8cTzPiu8f3n9rP5WLzx_n7WxRWsHUWMrKaSXcyinQdsVYo4CCYFI2XFukjdNL4axcWag0twJYXaMElChzngPnZ8Xbg-52Wva4shjGATqzHXwPw85E8Ob_l-A3Zh1_Gy14oyuaBc6PAkO8mTCNpvfJ5mkgYB7RVHWtVKMYqzP6-oCuoUPjg4tZ0e5xM1MNFawR1Z66eIDKa4W9t3H_kTn_UIEdYkoDuvvuGTV7a5iDNczRGrng1b8z3-N_vcDvANcNt0M</recordid><startdate>20220902</startdate><enddate>20220902</enddate><creator>Murugesan, Karthikeyan</creator><creator>Jin, Dexter X</creator><creator>Comment, Leah A</creator><creator>Fabrizio, David</creator><creator>Hegde, Priti S</creator><creator>Elvin, Julia A</creator><creator>Alexander, Brian</creator><creator>Levy, Mia A</creator><creator>Frampton, Garrett M</creator><creator>Montesion, Meagan</creator><creator>Roychowdhury, Sameek</creator><creator>Kurzrock, Razelle</creator><creator>Ross, Jeffrey S</creator><creator>Albacker, Lee A</creator><creator>Huang, Richard S P</creator><general>Oxford University Press</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8395-5168</orcidid><orcidid>https://orcid.org/0000-0002-5070-1783</orcidid><orcidid>https://orcid.org/0000-0002-2275-1126</orcidid></search><sort><creationdate>20220902</creationdate><title>Association of CD274 (PD-L1) Copy Number Changes with Immune Checkpoint Inhibitor Clinical Benefit in Non-Squamous Non-Small Cell Lung Cancer</title><author>Murugesan, Karthikeyan ; Jin, Dexter X ; Comment, Leah A ; Fabrizio, David ; Hegde, Priti S ; Elvin, Julia A ; Alexander, Brian ; Levy, Mia A ; Frampton, Garrett M ; Montesion, Meagan ; Roychowdhury, Sameek ; Kurzrock, Razelle ; Ross, Jeffrey S ; Albacker, Lee A ; Huang, Richard S P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c417t-52f974fdf7a9cd1187a0a4155839ce08f9b4fc5dca293c4a166e5ae5e5b4f3a33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Cancer Diagnostics and Molecular Pathology</topic><topic>Copy number variations</topic><topic>Diagnosis</topic><topic>Drug therapy</topic><topic>Health aspects</topic><topic>Influence</topic><topic>Lung cancer, Non-small cell</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Murugesan, Karthikeyan</creatorcontrib><creatorcontrib>Jin, Dexter X</creatorcontrib><creatorcontrib>Comment, Leah A</creatorcontrib><creatorcontrib>Fabrizio, David</creatorcontrib><creatorcontrib>Hegde, Priti S</creatorcontrib><creatorcontrib>Elvin, Julia A</creatorcontrib><creatorcontrib>Alexander, Brian</creatorcontrib><creatorcontrib>Levy, Mia A</creatorcontrib><creatorcontrib>Frampton, Garrett M</creatorcontrib><creatorcontrib>Montesion, Meagan</creatorcontrib><creatorcontrib>Roychowdhury, Sameek</creatorcontrib><creatorcontrib>Kurzrock, Razelle</creatorcontrib><creatorcontrib>Ross, Jeffrey S</creatorcontrib><creatorcontrib>Albacker, Lee A</creatorcontrib><creatorcontrib>Huang, Richard S P</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The oncologist (Dayton, Ohio)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Murugesan, Karthikeyan</au><au>Jin, Dexter X</au><au>Comment, Leah A</au><au>Fabrizio, David</au><au>Hegde, Priti S</au><au>Elvin, Julia A</au><au>Alexander, Brian</au><au>Levy, Mia A</au><au>Frampton, Garrett M</au><au>Montesion, Meagan</au><au>Roychowdhury, Sameek</au><au>Kurzrock, Razelle</au><au>Ross, Jeffrey S</au><au>Albacker, Lee A</au><au>Huang, Richard S P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of CD274 (PD-L1) Copy Number Changes with Immune Checkpoint Inhibitor Clinical Benefit in Non-Squamous Non-Small Cell Lung Cancer</atitle><jtitle>The oncologist (Dayton, Ohio)</jtitle><addtitle>Oncologist</addtitle><date>2022-09-02</date><risdate>2022</risdate><volume>27</volume><issue>9</issue><spage>732</spage><epage>739</epage><pages>732-739</pages><issn>1083-7159</issn><eissn>1549-490X</eissn><abstract>We sought to characterize response to immune checkpoint inhibitor (ICI) in non-squamous non-small cell lung cancer (NSCLC) across various CD274 copy number gain and loss thresholds and identify an optimal cutoff.
A de-identified nationwide (US) real-world clinico-genomic database was leveraged to study 621 non-squamous NSCLC patients treated with ICI. All patients received second-line ICI monotherapy and underwent comprehensive genomic profiling as part of routine clinical care. Overall survival (OS) from start of ICI, for CD274 copy number gain and loss cohorts across varying copy number thresholds, were assessed.
Among the 621 patients, patients with a CD274 CN greater than or equal to specimen ploidy +2 (N = 29) had a significantly higher median (m) OS when compared with the rest of the cohort (N = 592; 16.1 [8.9-37.3] vs 8.6 [7.1-10.9] months, hazard ratio (HR) = 0.6 [0.4-1.0], P-value = .05). Patients with a CD274 copy number less than specimen ploidy (N = 299) trended toward a lower mOS when compared to the rest of the cohort (N = 322; 7.5 [5.9-11.3] vs 9.6 [7.9-12.8] months, HR = 0.9 [0.7-1.1], P-value = .3).
This work shows that CD274 copy number gains at varying thresholds predict different response to ICI blockade in non-squamous NSCLC. Considering these data, prospective clinical trials should further validate these findings, specifically in the context of PD-L1 IHC test results.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>35598202</pmid><doi>10.1093/oncolo/oyac096</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0001-8395-5168</orcidid><orcidid>https://orcid.org/0000-0002-5070-1783</orcidid><orcidid>https://orcid.org/0000-0002-2275-1126</orcidid><oa>free_for_read</oa></addata></record> |
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| source | DOAJ Directory of Open Access Journals; Oxford Journals Open Access Collection; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Cancer Diagnostics and Molecular Pathology Copy number variations Diagnosis Drug therapy Health aspects Influence Lung cancer, Non-small cell |
| title | Association of CD274 (PD-L1) Copy Number Changes with Immune Checkpoint Inhibitor Clinical Benefit in Non-Squamous Non-Small Cell Lung Cancer |
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