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Molecular subtype-specific efficacy of anti-EGFR therapy in colorectal cancer is dependent on the chemotherapy backbone
Background Patient selection for addition of anti-EGFR therapy to chemotherapy for patients with RAS and BRAF wildtype metastatic colorectal cancer can still be optimised. Here we investigate the effect of anti-EGFR therapy on survival in different consensus molecular subtypes (CMSs) and stratified...
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| Published in: | British journal of cancer 2021-10, Vol.125 (8), p.1080-1088 |
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| container_title | British journal of cancer |
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| creator | ten Hoorn, Sanne Sommeijer, Dirkje W. Elliott, Faye Fisher, David de Back, Tim R. Trinh, Anne Koens, Lianne Maughan, Tim Seligmann, Jenny Seymour, Matthew T. Quirke, Phil Adams, Richard Richman, Susan D. Punt, Cornelis J. A. Vermeulen, Louis |
| description | Background
Patient selection for addition of anti-EGFR therapy to chemotherapy for patients with
RAS
and
BRAF
wildtype metastatic colorectal cancer can still be optimised. Here we investigate the effect of anti-EGFR therapy on survival in different consensus molecular subtypes (CMSs) and stratified by primary tumour location.
Methods
Retrospective analyses, using the immunohistochemistry-based CMS classifier, were performed in the COIN (first-line oxaliplatin backbone with or without cetuximab) and PICCOLO trial (second-line irinotecan with or without panitumumab). Tumour tissue was available for 323 patients (20%) and 349 (41%), respectively.
Results
When using an irinotecan backbone, anti-EGFR therapy is effective in both CMS2/3 and CMS4 in left-sided primary tumours (progression-free survival (PFS): HR 0.44, 95% CI 0.26–0.75,
P
= 0.003 and HR 0.12, 95% CI 0.04–0.36,
P
|
| doi_str_mv | 10.1038/s41416-021-01477-9 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8505637</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2551211760</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-c8d209616cd77275bc8e65dd5fbca2886c18499009b274a7c15f2e9de9fb4bcd3</originalsourceid><addsrcrecordid>eNp9kU9vFSEUxYnR2Gf1C7gwJG7coMDAwGxMTNNWkxoTo2vC3LnTR50HI8zUvG8v9bX1z8INhNzfOdyTQ8hzwV8L3tg3RQklWsalYFwoY1j3gGyEbiQTVpqHZMM5N4x3kh-RJ6Vc1WfHrXlMjholdWON2pAfH9OEsE4-07L2y35GVmaEMAagONbTw56mkfq4BHZ6fvaZLlvMft7TECmkKWWExU8UfATMNBQ64IxxwLjQFG9gClvcpTtV7-FbnyI-JY9GPxV8dnsfk69np19O3rOLT-cfTt5dMFBGLQzsIHnXihYGY6TRPVhs9TDosQcvrW1BWNV1NVgvjfIGhB4ldgN2Y696GJpj8vbgO6_9Dgeoe2U_uTmHnc97l3xwf09i2LrLdO2s5rptTDV4dWuQ0_cVy-J2oQBOk4-Y1uKk1kIKYVpe0Zf_oFdpzbHGq5TlthqaplLyQEFOpWQc75cR3N306g69utqr-9Wr66roxZ8x7iV3RVagOQCljuIl5t9__8f2J6YcsG4</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2580805673</pqid></control><display><type>article</type><title>Molecular subtype-specific efficacy of anti-EGFR therapy in colorectal cancer is dependent on the chemotherapy backbone</title><source>PubMed (Medline)</source><source>Springer Nature</source><creator>ten Hoorn, Sanne ; Sommeijer, Dirkje W. ; Elliott, Faye ; Fisher, David ; de Back, Tim R. ; Trinh, Anne ; Koens, Lianne ; Maughan, Tim ; Seligmann, Jenny ; Seymour, Matthew T. ; Quirke, Phil ; Adams, Richard ; Richman, Susan D. ; Punt, Cornelis J. A. ; Vermeulen, Louis</creator><creatorcontrib>ten Hoorn, Sanne ; Sommeijer, Dirkje W. ; Elliott, Faye ; Fisher, David ; de Back, Tim R. ; Trinh, Anne ; Koens, Lianne ; Maughan, Tim ; Seligmann, Jenny ; Seymour, Matthew T. ; Quirke, Phil ; Adams, Richard ; Richman, Susan D. ; Punt, Cornelis J. A. ; Vermeulen, Louis</creatorcontrib><description>Background
Patient selection for addition of anti-EGFR therapy to chemotherapy for patients with
RAS
and
BRAF
wildtype metastatic colorectal cancer can still be optimised. Here we investigate the effect of anti-EGFR therapy on survival in different consensus molecular subtypes (CMSs) and stratified by primary tumour location.
Methods
Retrospective analyses, using the immunohistochemistry-based CMS classifier, were performed in the COIN (first-line oxaliplatin backbone with or without cetuximab) and PICCOLO trial (second-line irinotecan with or without panitumumab). Tumour tissue was available for 323 patients (20%) and 349 (41%), respectively.
Results
When using an irinotecan backbone, anti-EGFR therapy is effective in both CMS2/3 and CMS4 in left-sided primary tumours (progression-free survival (PFS): HR 0.44, 95% CI 0.26–0.75,
P
= 0.003 and HR 0.12, 95% CI 0.04–0.36,
P
< 0.001, respectively) and in CMS4 right-sided tumours (PFS HR 0.17, 95% CI 0.04–0.71,
P
= 0.02). Efficacy using an oxaliplatin backbone was restricted to left-sided CMS2/3 tumours (HR 0.57, 95% CI 0.36–0.96,
P
= 0.034).
Conclusions
The subtype-specific efficacy of anti-EGFR therapy is dependent on the chemotherapy backbone. This may provide the possibility of subtype-specific treatment strategies for a more optimal use of anti-EGFR therapy.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/s41416-021-01477-9</identifier><identifier>PMID: 34253874</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>692/4028/67/1059/99 ; 692/4028/67/1504/1885 ; 692/4028/67/322 ; Aged ; Antineoplastic Combined Chemotherapy Protocols - pharmacology ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Cetuximab - pharmacology ; Cetuximab - therapeutic use ; Chemotherapy ; Clinical Trials as Topic ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - classification ; Colorectal Neoplasms - drug therapy ; Colorectal Neoplasms - genetics ; Drug Resistance ; Epidemiology ; Epidermal growth factor receptors ; ErbB Receptors - antagonists & inhibitors ; Female ; Humans ; Immunohistochemistry ; Irinotecan ; Irinotecan - pharmacology ; Irinotecan - therapeutic use ; Male ; Metastases ; Middle Aged ; Molecular Medicine ; Neoplasm Metastasis ; Oncology ; Oxaliplatin ; Oxaliplatin - pharmacology ; Oxaliplatin - therapeutic use ; Panitumumab - pharmacology ; Panitumumab - therapeutic use ; Patients ; Protein Kinase Inhibitors - pharmacology ; Protein Kinase Inhibitors - therapeutic use ; Proto-Oncogene Proteins B-raf - genetics ; ras Proteins - genetics ; Retrospective Studies ; Survival ; Survival Analysis ; Treatment Outcome ; Tumors</subject><ispartof>British journal of cancer, 2021-10, Vol.125 (8), p.1080-1088</ispartof><rights>The Author(s) 2021</rights><rights>2021. The Author(s).</rights><rights>The Author(s) 2021. 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-c474t-c8d209616cd77275bc8e65dd5fbca2886c18499009b274a7c15f2e9de9fb4bcd3</citedby><cites>FETCH-LOGICAL-c474t-c8d209616cd77275bc8e65dd5fbca2886c18499009b274a7c15f2e9de9fb4bcd3</cites><orcidid>0000-0002-6066-789X ; 0000-0001-9553-6091 ; 0000-0003-4379-6005</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/PMC8505637/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505637/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34253874$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ten Hoorn, Sanne</creatorcontrib><creatorcontrib>Sommeijer, Dirkje W.</creatorcontrib><creatorcontrib>Elliott, Faye</creatorcontrib><creatorcontrib>Fisher, David</creatorcontrib><creatorcontrib>de Back, Tim R.</creatorcontrib><creatorcontrib>Trinh, Anne</creatorcontrib><creatorcontrib>Koens, Lianne</creatorcontrib><creatorcontrib>Maughan, Tim</creatorcontrib><creatorcontrib>Seligmann, Jenny</creatorcontrib><creatorcontrib>Seymour, Matthew T.</creatorcontrib><creatorcontrib>Quirke, Phil</creatorcontrib><creatorcontrib>Adams, Richard</creatorcontrib><creatorcontrib>Richman, Susan D.</creatorcontrib><creatorcontrib>Punt, Cornelis J. A.</creatorcontrib><creatorcontrib>Vermeulen, Louis</creatorcontrib><title>Molecular subtype-specific efficacy of anti-EGFR therapy in colorectal cancer is dependent on the chemotherapy backbone</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Background
Patient selection for addition of anti-EGFR therapy to chemotherapy for patients with
RAS
and
BRAF
wildtype metastatic colorectal cancer can still be optimised. Here we investigate the effect of anti-EGFR therapy on survival in different consensus molecular subtypes (CMSs) and stratified by primary tumour location.
Methods
Retrospective analyses, using the immunohistochemistry-based CMS classifier, were performed in the COIN (first-line oxaliplatin backbone with or without cetuximab) and PICCOLO trial (second-line irinotecan with or without panitumumab). Tumour tissue was available for 323 patients (20%) and 349 (41%), respectively.
Results
When using an irinotecan backbone, anti-EGFR therapy is effective in both CMS2/3 and CMS4 in left-sided primary tumours (progression-free survival (PFS): HR 0.44, 95% CI 0.26–0.75,
P
= 0.003 and HR 0.12, 95% CI 0.04–0.36,
P
< 0.001, respectively) and in CMS4 right-sided tumours (PFS HR 0.17, 95% CI 0.04–0.71,
P
= 0.02). Efficacy using an oxaliplatin backbone was restricted to left-sided CMS2/3 tumours (HR 0.57, 95% CI 0.36–0.96,
P
= 0.034).
Conclusions
The subtype-specific efficacy of anti-EGFR therapy is dependent on the chemotherapy backbone. This may provide the possibility of subtype-specific treatment strategies for a more optimal use of anti-EGFR therapy.</description><subject>692/4028/67/1059/99</subject><subject>692/4028/67/1504/1885</subject><subject>692/4028/67/322</subject><subject>Aged</subject><subject>Antineoplastic Combined Chemotherapy Protocols - pharmacology</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Cetuximab - pharmacology</subject><subject>Cetuximab - therapeutic use</subject><subject>Chemotherapy</subject><subject>Clinical Trials as Topic</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - classification</subject><subject>Colorectal Neoplasms - drug therapy</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Drug Resistance</subject><subject>Epidemiology</subject><subject>Epidermal growth factor receptors</subject><subject>ErbB Receptors - antagonists & inhibitors</subject><subject>Female</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Irinotecan</subject><subject>Irinotecan - pharmacology</subject><subject>Irinotecan - therapeutic use</subject><subject>Male</subject><subject>Metastases</subject><subject>Middle Aged</subject><subject>Molecular Medicine</subject><subject>Neoplasm Metastasis</subject><subject>Oncology</subject><subject>Oxaliplatin</subject><subject>Oxaliplatin - pharmacology</subject><subject>Oxaliplatin - therapeutic use</subject><subject>Panitumumab - pharmacology</subject><subject>Panitumumab - therapeutic use</subject><subject>Patients</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Protein Kinase Inhibitors - therapeutic use</subject><subject>Proto-Oncogene Proteins B-raf - genetics</subject><subject>ras Proteins - genetics</subject><subject>Retrospective Studies</subject><subject>Survival</subject><subject>Survival Analysis</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kU9vFSEUxYnR2Gf1C7gwJG7coMDAwGxMTNNWkxoTo2vC3LnTR50HI8zUvG8v9bX1z8INhNzfOdyTQ8hzwV8L3tg3RQklWsalYFwoY1j3gGyEbiQTVpqHZMM5N4x3kh-RJ6Vc1WfHrXlMjholdWON2pAfH9OEsE4-07L2y35GVmaEMAagONbTw56mkfq4BHZ6fvaZLlvMft7TECmkKWWExU8UfATMNBQ64IxxwLjQFG9gClvcpTtV7-FbnyI-JY9GPxV8dnsfk69np19O3rOLT-cfTt5dMFBGLQzsIHnXihYGY6TRPVhs9TDosQcvrW1BWNV1NVgvjfIGhB4ldgN2Y696GJpj8vbgO6_9Dgeoe2U_uTmHnc97l3xwf09i2LrLdO2s5rptTDV4dWuQ0_cVy-J2oQBOk4-Y1uKk1kIKYVpe0Zf_oFdpzbHGq5TlthqaplLyQEFOpWQc75cR3N306g69utqr-9Wr66roxZ8x7iV3RVagOQCljuIl5t9__8f2J6YcsG4</recordid><startdate>20211012</startdate><enddate>20211012</enddate><creator>ten Hoorn, Sanne</creator><creator>Sommeijer, Dirkje W.</creator><creator>Elliott, Faye</creator><creator>Fisher, David</creator><creator>de Back, Tim R.</creator><creator>Trinh, Anne</creator><creator>Koens, Lianne</creator><creator>Maughan, Tim</creator><creator>Seligmann, Jenny</creator><creator>Seymour, Matthew T.</creator><creator>Quirke, Phil</creator><creator>Adams, Richard</creator><creator>Richman, Susan D.</creator><creator>Punt, Cornelis J. A.</creator><creator>Vermeulen, Louis</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</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>7RV</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</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>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-6066-789X</orcidid><orcidid>https://orcid.org/0000-0001-9553-6091</orcidid><orcidid>https://orcid.org/0000-0003-4379-6005</orcidid></search><sort><creationdate>20211012</creationdate><title>Molecular subtype-specific efficacy of anti-EGFR therapy in colorectal cancer is dependent on the chemotherapy backbone</title><author>ten Hoorn, Sanne ; Sommeijer, Dirkje W. ; Elliott, Faye ; Fisher, David ; de Back, Tim R. ; Trinh, Anne ; Koens, Lianne ; Maughan, Tim ; Seligmann, Jenny ; Seymour, Matthew T. ; Quirke, Phil ; Adams, Richard ; Richman, Susan D. ; Punt, Cornelis J. A. ; Vermeulen, Louis</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-c8d209616cd77275bc8e65dd5fbca2886c18499009b274a7c15f2e9de9fb4bcd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>692/4028/67/1059/99</topic><topic>692/4028/67/1504/1885</topic><topic>692/4028/67/322</topic><topic>Aged</topic><topic>Antineoplastic Combined Chemotherapy Protocols - pharmacology</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Cetuximab - pharmacology</topic><topic>Cetuximab - therapeutic use</topic><topic>Chemotherapy</topic><topic>Clinical Trials as Topic</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - classification</topic><topic>Colorectal Neoplasms - drug therapy</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Drug Resistance</topic><topic>Epidemiology</topic><topic>Epidermal growth factor receptors</topic><topic>ErbB Receptors - antagonists & inhibitors</topic><topic>Female</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Irinotecan</topic><topic>Irinotecan - pharmacology</topic><topic>Irinotecan - therapeutic use</topic><topic>Male</topic><topic>Metastases</topic><topic>Middle Aged</topic><topic>Molecular Medicine</topic><topic>Neoplasm Metastasis</topic><topic>Oncology</topic><topic>Oxaliplatin</topic><topic>Oxaliplatin - pharmacology</topic><topic>Oxaliplatin - therapeutic use</topic><topic>Panitumumab - pharmacology</topic><topic>Panitumumab - therapeutic use</topic><topic>Patients</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Protein Kinase Inhibitors - therapeutic use</topic><topic>Proto-Oncogene Proteins B-raf - genetics</topic><topic>ras Proteins - genetics</topic><topic>Retrospective Studies</topic><topic>Survival</topic><topic>Survival Analysis</topic><topic>Treatment Outcome</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ten Hoorn, Sanne</creatorcontrib><creatorcontrib>Sommeijer, Dirkje W.</creatorcontrib><creatorcontrib>Elliott, Faye</creatorcontrib><creatorcontrib>Fisher, David</creatorcontrib><creatorcontrib>de Back, Tim R.</creatorcontrib><creatorcontrib>Trinh, Anne</creatorcontrib><creatorcontrib>Koens, Lianne</creatorcontrib><creatorcontrib>Maughan, Tim</creatorcontrib><creatorcontrib>Seligmann, Jenny</creatorcontrib><creatorcontrib>Seymour, Matthew T.</creatorcontrib><creatorcontrib>Quirke, Phil</creatorcontrib><creatorcontrib>Adams, Richard</creatorcontrib><creatorcontrib>Richman, Susan D.</creatorcontrib><creatorcontrib>Punt, Cornelis J. A.</creatorcontrib><creatorcontrib>Vermeulen, Louis</creatorcontrib><collection>SpringerOpen</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>ProQuest Nursing and Allied Health Journals</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Complete (ProQuest Database)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</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 UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</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><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ten Hoorn, Sanne</au><au>Sommeijer, Dirkje W.</au><au>Elliott, Faye</au><au>Fisher, David</au><au>de Back, Tim R.</au><au>Trinh, Anne</au><au>Koens, Lianne</au><au>Maughan, Tim</au><au>Seligmann, Jenny</au><au>Seymour, Matthew T.</au><au>Quirke, Phil</au><au>Adams, Richard</au><au>Richman, Susan D.</au><au>Punt, Cornelis J. A.</au><au>Vermeulen, Louis</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular subtype-specific efficacy of anti-EGFR therapy in colorectal cancer is dependent on the chemotherapy backbone</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2021-10-12</date><risdate>2021</risdate><volume>125</volume><issue>8</issue><spage>1080</spage><epage>1088</epage><pages>1080-1088</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><abstract>Background
Patient selection for addition of anti-EGFR therapy to chemotherapy for patients with
RAS
and
BRAF
wildtype metastatic colorectal cancer can still be optimised. Here we investigate the effect of anti-EGFR therapy on survival in different consensus molecular subtypes (CMSs) and stratified by primary tumour location.
Methods
Retrospective analyses, using the immunohistochemistry-based CMS classifier, were performed in the COIN (first-line oxaliplatin backbone with or without cetuximab) and PICCOLO trial (second-line irinotecan with or without panitumumab). Tumour tissue was available for 323 patients (20%) and 349 (41%), respectively.
Results
When using an irinotecan backbone, anti-EGFR therapy is effective in both CMS2/3 and CMS4 in left-sided primary tumours (progression-free survival (PFS): HR 0.44, 95% CI 0.26–0.75,
P
= 0.003 and HR 0.12, 95% CI 0.04–0.36,
P
< 0.001, respectively) and in CMS4 right-sided tumours (PFS HR 0.17, 95% CI 0.04–0.71,
P
= 0.02). Efficacy using an oxaliplatin backbone was restricted to left-sided CMS2/3 tumours (HR 0.57, 95% CI 0.36–0.96,
P
= 0.034).
Conclusions
The subtype-specific efficacy of anti-EGFR therapy is dependent on the chemotherapy backbone. This may provide the possibility of subtype-specific treatment strategies for a more optimal use of anti-EGFR therapy.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>34253874</pmid><doi>10.1038/s41416-021-01477-9</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-6066-789X</orcidid><orcidid>https://orcid.org/0000-0001-9553-6091</orcidid><orcidid>https://orcid.org/0000-0003-4379-6005</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0007-0920 |
| ispartof | British journal of cancer, 2021-10, Vol.125 (8), p.1080-1088 |
| issn | 0007-0920 1532-1827 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8505637 |
| source | PubMed (Medline); Springer Nature |
| subjects | 692/4028/67/1059/99 692/4028/67/1504/1885 692/4028/67/322 Aged Antineoplastic Combined Chemotherapy Protocols - pharmacology Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biomedical and Life Sciences Biomedicine Cancer Research Cetuximab - pharmacology Cetuximab - therapeutic use Chemotherapy Clinical Trials as Topic Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - classification Colorectal Neoplasms - drug therapy Colorectal Neoplasms - genetics Drug Resistance Epidemiology Epidermal growth factor receptors ErbB Receptors - antagonists & inhibitors Female Humans Immunohistochemistry Irinotecan Irinotecan - pharmacology Irinotecan - therapeutic use Male Metastases Middle Aged Molecular Medicine Neoplasm Metastasis Oncology Oxaliplatin Oxaliplatin - pharmacology Oxaliplatin - therapeutic use Panitumumab - pharmacology Panitumumab - therapeutic use Patients Protein Kinase Inhibitors - pharmacology Protein Kinase Inhibitors - therapeutic use Proto-Oncogene Proteins B-raf - genetics ras Proteins - genetics Retrospective Studies Survival Survival Analysis Treatment Outcome Tumors |
| title | Molecular subtype-specific efficacy of anti-EGFR therapy in colorectal cancer is dependent on the chemotherapy backbone |
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