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Biomarkers predictive of response to pembrolizumab in head and neck cancer
Background We performed an integrated biomarker evaluation in pembrolizumab‐treated patients with R/M HNSCC enrolled in KEYNOTE‐012 or KEYNOTE‐055. The relationship between biomarkers and HPV status was explored. Methods We evaluated PD‐L1 (combined positive score [CPS]), TMB, T‐cell‐inflamed gene e...
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| Published in: | Cancer medicine (Malden, MA) MA), 2023-03, Vol.12 (6), p.6603-6614 |
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| creator | Pfister, David G. Haddad, Robert I. Worden, Francis P. Weiss, Jared Mehra, Ranee Chow, Laura Q. M. Liu, Stephen V. Kang, Hyunseok Saba, Nabil F. Wirth, Lori J. Sukari, Ammar Massarelli, Erminia Ayers, Mark Albright, Andrew Webber, Andrea L. Mogg, Robin Lunceford, Jared Huang, Lingkang Cristescu, Razvan Cheng, Jonathan Seiwert, Tanguy Y. Bauml, Joshua M. |
| description | Background
We performed an integrated biomarker evaluation in pembrolizumab‐treated patients with R/M HNSCC enrolled in KEYNOTE‐012 or KEYNOTE‐055. The relationship between biomarkers and HPV status was explored.
Methods
We evaluated PD‐L1 (combined positive score [CPS]), TMB, T‐cell‐inflamed gene expression profile (TcellinfGEP), and HPV status. Associations between biomarkers were evaluated by logistic regression (ORR) and Cox regression (PFS, OS).
Results
Two hundred and fifty‐seven patients (KEYNOTE‐012, n = 106; KEYNOTE‐055, n = 151) had TMB data available; of these, 254 had PD‐L1 and 236 had TcellinfGEP. TMB, PD‐L1, and TcellinfGEP were each significantly associated with ORR (p |
| doi_str_mv | 10.1002/cam4.5434 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_41ead9902e374b769caeb779819059f4</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_41ead9902e374b769caeb779819059f4</doaj_id><sourcerecordid>2753301670</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5104-e86cbf24231080ec8a1b4a0e5a19006d14626933f5c1b1442bdf01d0515093773</originalsourceid><addsrcrecordid>eNp1kU1v1DAQhiMEolXpgT-ALHGBw7bjj9jxCZUVH0VFXOBsOc6k9Taxg50Utb--3m6pWiR8sWU_euYdT1W9pnBEAdixs6M4qgUXz6p9BqJeKcnF80fnveow5w2UpYBJRV9We1wKpSVX-9W3jz6ONl1iymRK2Hk3-ysksScJ8xRDRjJHMuHYpjj4m2W0LfGBXKDtiA0dCeguibPBYXpVvejtkPHwfj-ofn3-9HP9dXX248vp-uRs5WoKYoWNdG3PBOMUGkDXWNoKC1hbqgFkR4VkUnPe1462VAjWdj3QDmpag-ZK8YPqdOftot2YKfmS_9pE683dRUznxqbZuwGNoCWn1sCQK9EqqZ3FVindlFK17kVxfdi5pqUdsXMY5mSHJ9KnL8FfmPN4ZcrXSwUNLYZ394YUfy-YZzP67HAYbMC4ZMNUzTnQAhf07T_oJi4plL8qVGmNSyW37b3fUS7FnBP2D2kobMsys5242U68sG8ex38g_863AMc74I8f8Pr_JrM--S7ulLdgWrKl</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2793736767</pqid></control><display><type>article</type><title>Biomarkers predictive of response to pembrolizumab in head and neck cancer</title><source>PubMed (Medline)</source><source>Publicly Available Content (ProQuest)</source><source>Wiley Open Access</source><creator>Pfister, David G. ; Haddad, Robert I. ; Worden, Francis P. ; Weiss, Jared ; Mehra, Ranee ; Chow, Laura Q. M. ; Liu, Stephen V. ; Kang, Hyunseok ; Saba, Nabil F. ; Wirth, Lori J. ; Sukari, Ammar ; Massarelli, Erminia ; Ayers, Mark ; Albright, Andrew ; Webber, Andrea L. ; Mogg, Robin ; Lunceford, Jared ; Huang, Lingkang ; Cristescu, Razvan ; Cheng, Jonathan ; Seiwert, Tanguy Y. ; Bauml, Joshua M.</creator><creatorcontrib>Pfister, David G. ; Haddad, Robert I. ; Worden, Francis P. ; Weiss, Jared ; Mehra, Ranee ; Chow, Laura Q. M. ; Liu, Stephen V. ; Kang, Hyunseok ; Saba, Nabil F. ; Wirth, Lori J. ; Sukari, Ammar ; Massarelli, Erminia ; Ayers, Mark ; Albright, Andrew ; Webber, Andrea L. ; Mogg, Robin ; Lunceford, Jared ; Huang, Lingkang ; Cristescu, Razvan ; Cheng, Jonathan ; Seiwert, Tanguy Y. ; Bauml, Joshua M.</creatorcontrib><description>Background
We performed an integrated biomarker evaluation in pembrolizumab‐treated patients with R/M HNSCC enrolled in KEYNOTE‐012 or KEYNOTE‐055. The relationship between biomarkers and HPV status was explored.
Methods
We evaluated PD‐L1 (combined positive score [CPS]), TMB, T‐cell‐inflamed gene expression profile (TcellinfGEP), and HPV status. Associations between biomarkers were evaluated by logistic regression (ORR) and Cox regression (PFS, OS).
Results
Two hundred and fifty‐seven patients (KEYNOTE‐012, n = 106; KEYNOTE‐055, n = 151) had TMB data available; of these, 254 had PD‐L1 and 236 had TcellinfGEP. TMB, PD‐L1, and TcellinfGEP were each significantly associated with ORR (p < 0.01). Kaplan–Meier curves at prespecified cutoffs generally showed PFS and OS separation in the anticipated direction for these biomarkers, except for OS and TMB. TMB did not correlate with PD‐L1 or TcellinfGEP (Spearman ρ = −0.03 and ρ = −0.13, respectively); PD‐L1 and TcellinfGEP were moderately correlated (Spearman ρ = 0.47). In multivariate models, TMB, PD‐L1, and TcellinfGEP were each independently predictive for ORR (p < 0.001). ORR was higher in patients with high versus low levels of biomarkers when dichotomized using prespecified cutoffs; patients with higher versus lower levels of TMB and PD‐L1 or TMB and TcellinfGEP had the highest ORRs. Within HPV subgroups, higher versus lower distributions of biomarkers (PD‐L1, TMB, and TcellinfGEP) were associated with response. HPV detection by p16‐immunohistochemistry and WES showed good concordance (81%); results were generally similar by HPV status, regardless of the detection method.
Conclusions
TMB and the inflammatory biomarkers PD‐L1 and TcellinfGEP, assessed alone or together, may be useful for characterizing clinical response to pembrolizumab in R/M HNSCC.
TMB and inflammatory biomarkers PD‐L1 and T‐cell‐inflamed GEP, assessed alone or together, may be useful for characterizing clinical response to pembrolizumab in R/M HNSCC. Greater responses to pembrolizumab were associated with higher levels of TMB and inflammatory biomarkers than were lesser responses, an observation that was consistent regardless of HPV status, suggesting that biomarkers representing complementary measures of tumor antigenicity and a T‐cell‐inflamed tumor microenvironment may be useful in characterizing response to pembrolizumab.</description><identifier>ISSN: 2045-7634</identifier><identifier>EISSN: 2045-7634</identifier><identifier>DOI: 10.1002/cam4.5434</identifier><identifier>PMID: 36479637</identifier><language>eng</language><publisher>United States: John Wiley & Sons, Inc</publisher><subject>Antineoplastic Agents, Immunological - adverse effects ; B7-H1 Antigen ; biomarker ; Biomarkers ; Biomarkers, Tumor - genetics ; Cancer therapies ; Gene expression ; Head & neck cancer ; Head and Neck Neoplasms - drug therapy ; head and neck squamous cell carcinoma ; Human papillomavirus ; Humans ; Immunohistochemistry ; Immunotherapy ; Inflammation ; Lymphocytes T ; Monoclonal antibodies ; Mutation ; Papillomavirus Infections - complications ; Patients ; PD-L1 protein ; Pembrolizumab ; Regression analysis ; Squamous cell carcinoma ; Squamous Cell Carcinoma of Head and Neck - chemically induced ; Squamous Cell Carcinoma of Head and Neck - drug therapy ; Statistical analysis ; Targeted cancer therapy ; tumor microenvironment ; tumor mutational burden ; Tumors ; Viruses</subject><ispartof>Cancer medicine (Malden, MA), 2023-03, Vol.12 (6), p.6603-6614</ispartof><rights>2022 The Authors. published by John Wiley & Sons Ltd.</rights><rights>2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.</rights><rights>2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5104-e86cbf24231080ec8a1b4a0e5a19006d14626933f5c1b1442bdf01d0515093773</citedby><cites>FETCH-LOGICAL-c5104-e86cbf24231080ec8a1b4a0e5a19006d14626933f5c1b1442bdf01d0515093773</cites><orcidid>0000-0002-2109-3221 ; 0000-0003-4193-841X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2793736767/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2793736767?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,11541,25731,27901,27902,36989,36990,44566,46027,46451,53766,53768,74869</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36479637$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pfister, David G.</creatorcontrib><creatorcontrib>Haddad, Robert I.</creatorcontrib><creatorcontrib>Worden, Francis P.</creatorcontrib><creatorcontrib>Weiss, Jared</creatorcontrib><creatorcontrib>Mehra, Ranee</creatorcontrib><creatorcontrib>Chow, Laura Q. M.</creatorcontrib><creatorcontrib>Liu, Stephen V.</creatorcontrib><creatorcontrib>Kang, Hyunseok</creatorcontrib><creatorcontrib>Saba, Nabil F.</creatorcontrib><creatorcontrib>Wirth, Lori J.</creatorcontrib><creatorcontrib>Sukari, Ammar</creatorcontrib><creatorcontrib>Massarelli, Erminia</creatorcontrib><creatorcontrib>Ayers, Mark</creatorcontrib><creatorcontrib>Albright, Andrew</creatorcontrib><creatorcontrib>Webber, Andrea L.</creatorcontrib><creatorcontrib>Mogg, Robin</creatorcontrib><creatorcontrib>Lunceford, Jared</creatorcontrib><creatorcontrib>Huang, Lingkang</creatorcontrib><creatorcontrib>Cristescu, Razvan</creatorcontrib><creatorcontrib>Cheng, Jonathan</creatorcontrib><creatorcontrib>Seiwert, Tanguy Y.</creatorcontrib><creatorcontrib>Bauml, Joshua M.</creatorcontrib><title>Biomarkers predictive of response to pembrolizumab in head and neck cancer</title><title>Cancer medicine (Malden, MA)</title><addtitle>Cancer Med</addtitle><description>Background
We performed an integrated biomarker evaluation in pembrolizumab‐treated patients with R/M HNSCC enrolled in KEYNOTE‐012 or KEYNOTE‐055. The relationship between biomarkers and HPV status was explored.
Methods
We evaluated PD‐L1 (combined positive score [CPS]), TMB, T‐cell‐inflamed gene expression profile (TcellinfGEP), and HPV status. Associations between biomarkers were evaluated by logistic regression (ORR) and Cox regression (PFS, OS).
Results
Two hundred and fifty‐seven patients (KEYNOTE‐012, n = 106; KEYNOTE‐055, n = 151) had TMB data available; of these, 254 had PD‐L1 and 236 had TcellinfGEP. TMB, PD‐L1, and TcellinfGEP were each significantly associated with ORR (p < 0.01). Kaplan–Meier curves at prespecified cutoffs generally showed PFS and OS separation in the anticipated direction for these biomarkers, except for OS and TMB. TMB did not correlate with PD‐L1 or TcellinfGEP (Spearman ρ = −0.03 and ρ = −0.13, respectively); PD‐L1 and TcellinfGEP were moderately correlated (Spearman ρ = 0.47). In multivariate models, TMB, PD‐L1, and TcellinfGEP were each independently predictive for ORR (p < 0.001). ORR was higher in patients with high versus low levels of biomarkers when dichotomized using prespecified cutoffs; patients with higher versus lower levels of TMB and PD‐L1 or TMB and TcellinfGEP had the highest ORRs. Within HPV subgroups, higher versus lower distributions of biomarkers (PD‐L1, TMB, and TcellinfGEP) were associated with response. HPV detection by p16‐immunohistochemistry and WES showed good concordance (81%); results were generally similar by HPV status, regardless of the detection method.
Conclusions
TMB and the inflammatory biomarkers PD‐L1 and TcellinfGEP, assessed alone or together, may be useful for characterizing clinical response to pembrolizumab in R/M HNSCC.
TMB and inflammatory biomarkers PD‐L1 and T‐cell‐inflamed GEP, assessed alone or together, may be useful for characterizing clinical response to pembrolizumab in R/M HNSCC. Greater responses to pembrolizumab were associated with higher levels of TMB and inflammatory biomarkers than were lesser responses, an observation that was consistent regardless of HPV status, suggesting that biomarkers representing complementary measures of tumor antigenicity and a T‐cell‐inflamed tumor microenvironment may be useful in characterizing response to pembrolizumab.</description><subject>Antineoplastic Agents, Immunological - adverse effects</subject><subject>B7-H1 Antigen</subject><subject>biomarker</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Cancer therapies</subject><subject>Gene expression</subject><subject>Head & neck cancer</subject><subject>Head and Neck Neoplasms - drug therapy</subject><subject>head and neck squamous cell carcinoma</subject><subject>Human papillomavirus</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Immunotherapy</subject><subject>Inflammation</subject><subject>Lymphocytes T</subject><subject>Monoclonal antibodies</subject><subject>Mutation</subject><subject>Papillomavirus Infections - complications</subject><subject>Patients</subject><subject>PD-L1 protein</subject><subject>Pembrolizumab</subject><subject>Regression analysis</subject><subject>Squamous cell carcinoma</subject><subject>Squamous Cell Carcinoma of Head and Neck - chemically induced</subject><subject>Squamous Cell Carcinoma of Head and Neck - drug therapy</subject><subject>Statistical analysis</subject><subject>Targeted cancer therapy</subject><subject>tumor microenvironment</subject><subject>tumor mutational burden</subject><subject>Tumors</subject><subject>Viruses</subject><issn>2045-7634</issn><issn>2045-7634</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNp1kU1v1DAQhiMEolXpgT-ALHGBw7bjj9jxCZUVH0VFXOBsOc6k9Taxg50Utb--3m6pWiR8sWU_euYdT1W9pnBEAdixs6M4qgUXz6p9BqJeKcnF80fnveow5w2UpYBJRV9We1wKpSVX-9W3jz6ONl1iymRK2Hk3-ysksScJ8xRDRjJHMuHYpjj4m2W0LfGBXKDtiA0dCeguibPBYXpVvejtkPHwfj-ofn3-9HP9dXX248vp-uRs5WoKYoWNdG3PBOMUGkDXWNoKC1hbqgFkR4VkUnPe1462VAjWdj3QDmpag-ZK8YPqdOftot2YKfmS_9pE683dRUznxqbZuwGNoCWn1sCQK9EqqZ3FVindlFK17kVxfdi5pqUdsXMY5mSHJ9KnL8FfmPN4ZcrXSwUNLYZ394YUfy-YZzP67HAYbMC4ZMNUzTnQAhf07T_oJi4plL8qVGmNSyW37b3fUS7FnBP2D2kobMsys5242U68sG8ex38g_863AMc74I8f8Pr_JrM--S7ulLdgWrKl</recordid><startdate>202303</startdate><enddate>202303</enddate><creator>Pfister, David G.</creator><creator>Haddad, Robert I.</creator><creator>Worden, Francis P.</creator><creator>Weiss, Jared</creator><creator>Mehra, Ranee</creator><creator>Chow, Laura Q. M.</creator><creator>Liu, Stephen V.</creator><creator>Kang, Hyunseok</creator><creator>Saba, Nabil F.</creator><creator>Wirth, Lori J.</creator><creator>Sukari, Ammar</creator><creator>Massarelli, Erminia</creator><creator>Ayers, Mark</creator><creator>Albright, Andrew</creator><creator>Webber, Andrea L.</creator><creator>Mogg, Robin</creator><creator>Lunceford, Jared</creator><creator>Huang, Lingkang</creator><creator>Cristescu, Razvan</creator><creator>Cheng, Jonathan</creator><creator>Seiwert, Tanguy Y.</creator><creator>Bauml, Joshua M.</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><general>Wiley</general><scope>24P</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-2109-3221</orcidid><orcidid>https://orcid.org/0000-0003-4193-841X</orcidid></search><sort><creationdate>202303</creationdate><title>Biomarkers predictive of response to pembrolizumab in head and neck cancer</title><author>Pfister, David G. ; Haddad, Robert I. ; Worden, Francis P. ; Weiss, Jared ; Mehra, Ranee ; Chow, Laura Q. M. ; Liu, Stephen V. ; Kang, Hyunseok ; Saba, Nabil F. ; Wirth, Lori J. ; Sukari, Ammar ; Massarelli, Erminia ; Ayers, Mark ; Albright, Andrew ; Webber, Andrea L. ; Mogg, Robin ; Lunceford, Jared ; Huang, Lingkang ; Cristescu, Razvan ; Cheng, Jonathan ; Seiwert, Tanguy Y. ; Bauml, Joshua M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5104-e86cbf24231080ec8a1b4a0e5a19006d14626933f5c1b1442bdf01d0515093773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Antineoplastic Agents, Immunological - adverse effects</topic><topic>B7-H1 Antigen</topic><topic>biomarker</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Cancer therapies</topic><topic>Gene expression</topic><topic>Head & neck cancer</topic><topic>Head and Neck Neoplasms - drug therapy</topic><topic>head and neck squamous cell carcinoma</topic><topic>Human papillomavirus</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Immunotherapy</topic><topic>Inflammation</topic><topic>Lymphocytes T</topic><topic>Monoclonal antibodies</topic><topic>Mutation</topic><topic>Papillomavirus Infections - complications</topic><topic>Patients</topic><topic>PD-L1 protein</topic><topic>Pembrolizumab</topic><topic>Regression analysis</topic><topic>Squamous cell carcinoma</topic><topic>Squamous Cell Carcinoma of Head and Neck - chemically induced</topic><topic>Squamous Cell Carcinoma of Head and Neck - drug therapy</topic><topic>Statistical analysis</topic><topic>Targeted cancer therapy</topic><topic>tumor microenvironment</topic><topic>tumor mutational burden</topic><topic>Tumors</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pfister, David G.</creatorcontrib><creatorcontrib>Haddad, Robert I.</creatorcontrib><creatorcontrib>Worden, Francis P.</creatorcontrib><creatorcontrib>Weiss, Jared</creatorcontrib><creatorcontrib>Mehra, Ranee</creatorcontrib><creatorcontrib>Chow, Laura Q. M.</creatorcontrib><creatorcontrib>Liu, Stephen V.</creatorcontrib><creatorcontrib>Kang, Hyunseok</creatorcontrib><creatorcontrib>Saba, Nabil F.</creatorcontrib><creatorcontrib>Wirth, Lori J.</creatorcontrib><creatorcontrib>Sukari, Ammar</creatorcontrib><creatorcontrib>Massarelli, Erminia</creatorcontrib><creatorcontrib>Ayers, Mark</creatorcontrib><creatorcontrib>Albright, Andrew</creatorcontrib><creatorcontrib>Webber, Andrea L.</creatorcontrib><creatorcontrib>Mogg, Robin</creatorcontrib><creatorcontrib>Lunceford, Jared</creatorcontrib><creatorcontrib>Huang, Lingkang</creatorcontrib><creatorcontrib>Cristescu, Razvan</creatorcontrib><creatorcontrib>Cheng, Jonathan</creatorcontrib><creatorcontrib>Seiwert, Tanguy Y.</creatorcontrib><creatorcontrib>Bauml, Joshua M.</creatorcontrib><collection>Wiley 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>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Biological Science Database</collection><collection>Publicly Available Content (ProQuest)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>Cancer medicine (Malden, MA)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pfister, David G.</au><au>Haddad, Robert I.</au><au>Worden, Francis P.</au><au>Weiss, Jared</au><au>Mehra, Ranee</au><au>Chow, Laura Q. M.</au><au>Liu, Stephen V.</au><au>Kang, Hyunseok</au><au>Saba, Nabil F.</au><au>Wirth, Lori J.</au><au>Sukari, Ammar</au><au>Massarelli, Erminia</au><au>Ayers, Mark</au><au>Albright, Andrew</au><au>Webber, Andrea L.</au><au>Mogg, Robin</au><au>Lunceford, Jared</au><au>Huang, Lingkang</au><au>Cristescu, Razvan</au><au>Cheng, Jonathan</au><au>Seiwert, Tanguy Y.</au><au>Bauml, Joshua M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Biomarkers predictive of response to pembrolizumab in head and neck cancer</atitle><jtitle>Cancer medicine (Malden, MA)</jtitle><addtitle>Cancer Med</addtitle><date>2023-03</date><risdate>2023</risdate><volume>12</volume><issue>6</issue><spage>6603</spage><epage>6614</epage><pages>6603-6614</pages><issn>2045-7634</issn><eissn>2045-7634</eissn><abstract>Background
We performed an integrated biomarker evaluation in pembrolizumab‐treated patients with R/M HNSCC enrolled in KEYNOTE‐012 or KEYNOTE‐055. The relationship between biomarkers and HPV status was explored.
Methods
We evaluated PD‐L1 (combined positive score [CPS]), TMB, T‐cell‐inflamed gene expression profile (TcellinfGEP), and HPV status. Associations between biomarkers were evaluated by logistic regression (ORR) and Cox regression (PFS, OS).
Results
Two hundred and fifty‐seven patients (KEYNOTE‐012, n = 106; KEYNOTE‐055, n = 151) had TMB data available; of these, 254 had PD‐L1 and 236 had TcellinfGEP. TMB, PD‐L1, and TcellinfGEP were each significantly associated with ORR (p < 0.01). Kaplan–Meier curves at prespecified cutoffs generally showed PFS and OS separation in the anticipated direction for these biomarkers, except for OS and TMB. TMB did not correlate with PD‐L1 or TcellinfGEP (Spearman ρ = −0.03 and ρ = −0.13, respectively); PD‐L1 and TcellinfGEP were moderately correlated (Spearman ρ = 0.47). In multivariate models, TMB, PD‐L1, and TcellinfGEP were each independently predictive for ORR (p < 0.001). ORR was higher in patients with high versus low levels of biomarkers when dichotomized using prespecified cutoffs; patients with higher versus lower levels of TMB and PD‐L1 or TMB and TcellinfGEP had the highest ORRs. Within HPV subgroups, higher versus lower distributions of biomarkers (PD‐L1, TMB, and TcellinfGEP) were associated with response. HPV detection by p16‐immunohistochemistry and WES showed good concordance (81%); results were generally similar by HPV status, regardless of the detection method.
Conclusions
TMB and the inflammatory biomarkers PD‐L1 and TcellinfGEP, assessed alone or together, may be useful for characterizing clinical response to pembrolizumab in R/M HNSCC.
TMB and inflammatory biomarkers PD‐L1 and T‐cell‐inflamed GEP, assessed alone or together, may be useful for characterizing clinical response to pembrolizumab in R/M HNSCC. Greater responses to pembrolizumab were associated with higher levels of TMB and inflammatory biomarkers than were lesser responses, an observation that was consistent regardless of HPV status, suggesting that biomarkers representing complementary measures of tumor antigenicity and a T‐cell‐inflamed tumor microenvironment may be useful in characterizing response to pembrolizumab.</abstract><cop>United States</cop><pub>John Wiley & Sons, Inc</pub><pmid>36479637</pmid><doi>10.1002/cam4.5434</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-2109-3221</orcidid><orcidid>https://orcid.org/0000-0003-4193-841X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2045-7634 |
| ispartof | Cancer medicine (Malden, MA), 2023-03, Vol.12 (6), p.6603-6614 |
| issn | 2045-7634 2045-7634 |
| language | eng |
| recordid | cdi_doaj_primary_oai_doaj_org_article_41ead9902e374b769caeb779819059f4 |
| source | PubMed (Medline); Publicly Available Content (ProQuest); Wiley Open Access |
| subjects | Antineoplastic Agents, Immunological - adverse effects B7-H1 Antigen biomarker Biomarkers Biomarkers, Tumor - genetics Cancer therapies Gene expression Head & neck cancer Head and Neck Neoplasms - drug therapy head and neck squamous cell carcinoma Human papillomavirus Humans Immunohistochemistry Immunotherapy Inflammation Lymphocytes T Monoclonal antibodies Mutation Papillomavirus Infections - complications Patients PD-L1 protein Pembrolizumab Regression analysis Squamous cell carcinoma Squamous Cell Carcinoma of Head and Neck - chemically induced Squamous Cell Carcinoma of Head and Neck - drug therapy Statistical analysis Targeted cancer therapy tumor microenvironment tumor mutational burden Tumors Viruses |
| title | Biomarkers predictive of response to pembrolizumab in head and neck cancer |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T02%3A50%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Biomarkers%20predictive%20of%20response%20to%20pembrolizumab%20in%20head%20and%20neck%20cancer&rft.jtitle=Cancer%20medicine%20(Malden,%20MA)&rft.au=Pfister,%20David%20G.&rft.date=2023-03&rft.volume=12&rft.issue=6&rft.spage=6603&rft.epage=6614&rft.pages=6603-6614&rft.issn=2045-7634&rft.eissn=2045-7634&rft_id=info:doi/10.1002/cam4.5434&rft_dat=%3Cproquest_doaj_%3E2753301670%3C/proquest_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c5104-e86cbf24231080ec8a1b4a0e5a19006d14626933f5c1b1442bdf01d0515093773%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2793736767&rft_id=info:pmid/36479637&rfr_iscdi=true |