Immunotherapy revolutionises non-small-cell lung cancer therapy: Results, perspectives and new challenges
Abstract Immune checkpoint inhibitors (ICIs) are antibodies that target key signalling pathways such as programmed death 1 (PD1)/programmed death-ligands 1 and 2 (PDL1 and PDL2) to improve anti-tumour immune responses. Until recently, nivolumab was the only ICI validated for advanced non-small-cell...
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| Veröffentlicht in: | European journal of cancer (1990) 2017-06, Vol.78, p.16-23 |
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| container_title | European journal of cancer (1990) |
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| creator | Giroux Leprieur, Etienne Dumenil, Coraline Julie, Catherine Giraud, Violaine Dumoulin, Jennifer Labrune, Sylvie Chinet, Thierry |
| description | Abstract Immune checkpoint inhibitors (ICIs) are antibodies that target key signalling pathways such as programmed death 1 (PD1)/programmed death-ligands 1 and 2 (PDL1 and PDL2) to improve anti-tumour immune responses. Until recently, nivolumab was the only ICI validated for advanced non-small-cell lung cancer (NSCLC) in a second-line treatment setting. Results from recent phase II and phase III randomised trials testing other ICIs have been presented. In Keynote-024, pembrolizumab, an anti-PD1 antibody, was reported to have great efficacy in the first-line treatment of PDL1 ≥ 50% tumours (30% of screened tumours), with a progression-free survival (PFS, median) of 10.4 months versus 6.0 months with chemotherapy (CT; hazard ratio [HR] = 0.50; 95% confidence interval [95% CI] 0.37–0.68, P |
| doi_str_mv | 10.1016/j.ejca.2016.12.041 |
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Until recently, nivolumab was the only ICI validated for advanced non-small-cell lung cancer (NSCLC) in a second-line treatment setting. Results from recent phase II and phase III randomised trials testing other ICIs have been presented. In Keynote-024, pembrolizumab, an anti-PD1 antibody, was reported to have great efficacy in the first-line treatment of PDL1 ≥ 50% tumours (30% of screened tumours), with a progression-free survival (PFS, median) of 10.4 months versus 6.0 months with chemotherapy (CT; hazard ratio [HR] = 0.50; 95% confidence interval [95% CI] 0.37–0.68, P < 0.001), overall response rate (ORR) of 45% versus 28% with CT ( P = 0.0011), and a 1-year overall survival (OS) of around 70%. In contrast, Checkmate-026 reported that nivolumab failed to show any benefit compared with standard platinum-based CT, with a PFS (median) in the PDL1 ≥ 5% NSCLC group of 4.2 months (nivolumab) versus 5.9 months (CT; HR = 1.15: 95% CI 0.91–1.45, P = 0.25). No benefit was observed in the PDL1 ≥ 50% subgroup. An encouraging report of the efficacy of pembrolizumab in addition to CT in first-line treatment in unselected NSCLC was also presented (Keynote-021) with an ORR of 55% versus 29% with CT alone ( P = 0.0016). Atezolizumab, an anti-PDL1 antibody, showed efficacy for second-line treatment compared with docetaxel (OAK phase III study) with an OS (median) of 13.8 months versus 9.6 months with docetaxel. These results suggest a new paradigm for the treatment of advanced NSCLC using pembrolizumab for the first-line treatment of PDL1 ≥ 50% tumours.</description><identifier>ISSN: 0959-8049</identifier><identifier>EISSN: 1879-0852</identifier><identifier>DOI: 10.1016/j.ejca.2016.12.041</identifier><identifier>PMID: 28407528</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Antibodies ; Antibodies, Monoclonal - therapeutic use ; Antibodies, Monoclonal, Humanized - therapeutic use ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Apoptosis ; Atezolizumab ; B7-H1 Antigen - antagonists & inhibitors ; Cancer ; Cancer therapies ; Carcinoma, Non-Small-Cell Lung - therapy ; Chemotherapy ; Clinical trials ; Clinical Trials as Topic ; Confidence intervals ; Effectiveness ; Hematology, Oncology and Palliative Medicine ; Humans ; Immune checkpoint inhibitor ; Immune checkpoint inhibitors ; Immune response ; Immunotherapy ; Immunotherapy - methods ; Inhibitor drugs ; Ligands ; Lung cancer ; Lung Neoplasms - therapy ; Monoclonal antibodies ; Nivolumab ; Non-small cell lung carcinoma ; Non-small-cell lung cancer ; PD-1 protein ; PD1 ; PDL1 ; Pembrolizumab ; Platinum ; Programmed Cell Death 1 Ligand 2 Protein - antagonists & inhibitors ; Signal transduction ; Subgroups ; Survival ; Targeted cancer therapy ; Taxoids - therapeutic use ; Tumors</subject><ispartof>European journal of cancer (1990), 2017-06, Vol.78, p.16-23</ispartof><rights>2017</rights><rights>Copyright © 2017. Published by Elsevier Ltd.</rights><rights>Copyright Elsevier Science Ltd. Jun 2017</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c439t-1351027b1d9eb7b4895ed29d5976246c9ea9f2aeff9ea784091ca660f539e65f3</citedby><cites>FETCH-LOGICAL-c439t-1351027b1d9eb7b4895ed29d5976246c9ea9f2aeff9ea784091ca660f539e65f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0959804917308079$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28407528$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Giroux Leprieur, Etienne</creatorcontrib><creatorcontrib>Dumenil, Coraline</creatorcontrib><creatorcontrib>Julie, Catherine</creatorcontrib><creatorcontrib>Giraud, Violaine</creatorcontrib><creatorcontrib>Dumoulin, Jennifer</creatorcontrib><creatorcontrib>Labrune, Sylvie</creatorcontrib><creatorcontrib>Chinet, Thierry</creatorcontrib><title>Immunotherapy revolutionises non-small-cell lung cancer therapy: Results, perspectives and new challenges</title><title>European journal of cancer (1990)</title><addtitle>Eur J Cancer</addtitle><description>Abstract Immune checkpoint inhibitors (ICIs) are antibodies that target key signalling pathways such as programmed death 1 (PD1)/programmed death-ligands 1 and 2 (PDL1 and PDL2) to improve anti-tumour immune responses. Until recently, nivolumab was the only ICI validated for advanced non-small-cell lung cancer (NSCLC) in a second-line treatment setting. Results from recent phase II and phase III randomised trials testing other ICIs have been presented. In Keynote-024, pembrolizumab, an anti-PD1 antibody, was reported to have great efficacy in the first-line treatment of PDL1 ≥ 50% tumours (30% of screened tumours), with a progression-free survival (PFS, median) of 10.4 months versus 6.0 months with chemotherapy (CT; hazard ratio [HR] = 0.50; 95% confidence interval [95% CI] 0.37–0.68, P < 0.001), overall response rate (ORR) of 45% versus 28% with CT ( P = 0.0011), and a 1-year overall survival (OS) of around 70%. In contrast, Checkmate-026 reported that nivolumab failed to show any benefit compared with standard platinum-based CT, with a PFS (median) in the PDL1 ≥ 5% NSCLC group of 4.2 months (nivolumab) versus 5.9 months (CT; HR = 1.15: 95% CI 0.91–1.45, P = 0.25). No benefit was observed in the PDL1 ≥ 50% subgroup. An encouraging report of the efficacy of pembrolizumab in addition to CT in first-line treatment in unselected NSCLC was also presented (Keynote-021) with an ORR of 55% versus 29% with CT alone ( P = 0.0016). Atezolizumab, an anti-PDL1 antibody, showed efficacy for second-line treatment compared with docetaxel (OAK phase III study) with an OS (median) of 13.8 months versus 9.6 months with docetaxel. These results suggest a new paradigm for the treatment of advanced NSCLC using pembrolizumab for the first-line treatment of PDL1 ≥ 50% tumours.</description><subject>Antibodies</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Antibodies, Monoclonal, Humanized - therapeutic use</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Apoptosis</subject><subject>Atezolizumab</subject><subject>B7-H1 Antigen - antagonists & inhibitors</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Carcinoma, Non-Small-Cell Lung - therapy</subject><subject>Chemotherapy</subject><subject>Clinical trials</subject><subject>Clinical Trials as Topic</subject><subject>Confidence intervals</subject><subject>Effectiveness</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>Immune checkpoint inhibitor</subject><subject>Immune checkpoint inhibitors</subject><subject>Immune response</subject><subject>Immunotherapy</subject><subject>Immunotherapy - methods</subject><subject>Inhibitor drugs</subject><subject>Ligands</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - therapy</subject><subject>Monoclonal antibodies</subject><subject>Nivolumab</subject><subject>Non-small cell lung carcinoma</subject><subject>Non-small-cell lung cancer</subject><subject>PD-1 protein</subject><subject>PD1</subject><subject>PDL1</subject><subject>Pembrolizumab</subject><subject>Platinum</subject><subject>Programmed Cell Death 1 Ligand 2 Protein - antagonists & inhibitors</subject><subject>Signal transduction</subject><subject>Subgroups</subject><subject>Survival</subject><subject>Targeted cancer therapy</subject><subject>Taxoids - therapeutic use</subject><subject>Tumors</subject><issn>0959-8049</issn><issn>1879-0852</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kktr3TAQhUVpaW7S_oEuiqCbLmJHkh-SSimU0EcgEOhjLXTlcSJXllzJvuX--8jc2yyyyEqzON9o5pxB6A0lJSW0vRhKGIwuWa5LykpS02doQwWXBRENe442RDayEKSWJ-g0pYEQwkVNXqITlh_eMLFB9mocFx_mO4h62uMIu-CW2QZvEyTsgy_SqJ0rDDiH3eJvsdHeQMRH4gP-AWlxczrHE8Q0gZntLpPad9jDP2zuMg3-FtIr9KLXLsHr43uGfn_98uvye3F98-3q8vN1YepKzgWtGkoY39JOwpZvayEb6JjsGslbVrdGgpY909D3uVrXkdTotiV9U0lom746Q-8PfacY_i6QZjXatI6vPYQlKSqEaEWd_8nSd4-kQ1iiz9MpRhmRhHMps4odVCaGlCL0aop21HGvKFFrEGpQaxBqDUJRpnIQGXp7bL1sR-gekP_OZ8HHgwCyFzsLUSVjIVvb2ZhNVF2wT_f_9Ag3znprtPsDe0gPe1CVMqB-rqewXgLlFRGEy-oeuhivVg</recordid><startdate>20170601</startdate><enddate>20170601</enddate><creator>Giroux Leprieur, Etienne</creator><creator>Dumenil, Coraline</creator><creator>Julie, Catherine</creator><creator>Giraud, Violaine</creator><creator>Dumoulin, Jennifer</creator><creator>Labrune, Sylvie</creator><creator>Chinet, Thierry</creator><general>Elsevier Ltd</general><general>Elsevier Science Ltd</general><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>7TO</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>20170601</creationdate><title>Immunotherapy revolutionises non-small-cell lung cancer therapy: Results, perspectives and new challenges</title><author>Giroux Leprieur, Etienne ; Dumenil, Coraline ; Julie, Catherine ; Giraud, Violaine ; Dumoulin, Jennifer ; Labrune, Sylvie ; Chinet, Thierry</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c439t-1351027b1d9eb7b4895ed29d5976246c9ea9f2aeff9ea784091ca660f539e65f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Antibodies</topic><topic>Antibodies, Monoclonal - therapeutic use</topic><topic>Antibodies, Monoclonal, Humanized - therapeutic use</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Apoptosis</topic><topic>Atezolizumab</topic><topic>B7-H1 Antigen - antagonists & inhibitors</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Carcinoma, Non-Small-Cell Lung - therapy</topic><topic>Chemotherapy</topic><topic>Clinical trials</topic><topic>Clinical Trials as Topic</topic><topic>Confidence intervals</topic><topic>Effectiveness</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>Immune checkpoint inhibitor</topic><topic>Immune checkpoint inhibitors</topic><topic>Immune response</topic><topic>Immunotherapy</topic><topic>Immunotherapy - methods</topic><topic>Inhibitor drugs</topic><topic>Ligands</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - therapy</topic><topic>Monoclonal antibodies</topic><topic>Nivolumab</topic><topic>Non-small cell lung carcinoma</topic><topic>Non-small-cell lung cancer</topic><topic>PD-1 protein</topic><topic>PD1</topic><topic>PDL1</topic><topic>Pembrolizumab</topic><topic>Platinum</topic><topic>Programmed Cell Death 1 Ligand 2 Protein - antagonists & inhibitors</topic><topic>Signal transduction</topic><topic>Subgroups</topic><topic>Survival</topic><topic>Targeted cancer therapy</topic><topic>Taxoids - therapeutic use</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Giroux Leprieur, Etienne</creatorcontrib><creatorcontrib>Dumenil, Coraline</creatorcontrib><creatorcontrib>Julie, Catherine</creatorcontrib><creatorcontrib>Giraud, Violaine</creatorcontrib><creatorcontrib>Dumoulin, Jennifer</creatorcontrib><creatorcontrib>Labrune, Sylvie</creatorcontrib><creatorcontrib>Chinet, Thierry</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of cancer (1990)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Giroux Leprieur, Etienne</au><au>Dumenil, Coraline</au><au>Julie, Catherine</au><au>Giraud, Violaine</au><au>Dumoulin, Jennifer</au><au>Labrune, Sylvie</au><au>Chinet, Thierry</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunotherapy revolutionises non-small-cell lung cancer therapy: Results, perspectives and new challenges</atitle><jtitle>European journal of cancer (1990)</jtitle><addtitle>Eur J Cancer</addtitle><date>2017-06-01</date><risdate>2017</risdate><volume>78</volume><spage>16</spage><epage>23</epage><pages>16-23</pages><issn>0959-8049</issn><eissn>1879-0852</eissn><abstract>Abstract Immune checkpoint inhibitors (ICIs) are antibodies that target key signalling pathways such as programmed death 1 (PD1)/programmed death-ligands 1 and 2 (PDL1 and PDL2) to improve anti-tumour immune responses. Until recently, nivolumab was the only ICI validated for advanced non-small-cell lung cancer (NSCLC) in a second-line treatment setting. Results from recent phase II and phase III randomised trials testing other ICIs have been presented. In Keynote-024, pembrolizumab, an anti-PD1 antibody, was reported to have great efficacy in the first-line treatment of PDL1 ≥ 50% tumours (30% of screened tumours), with a progression-free survival (PFS, median) of 10.4 months versus 6.0 months with chemotherapy (CT; hazard ratio [HR] = 0.50; 95% confidence interval [95% CI] 0.37–0.68, P < 0.001), overall response rate (ORR) of 45% versus 28% with CT ( P = 0.0011), and a 1-year overall survival (OS) of around 70%. In contrast, Checkmate-026 reported that nivolumab failed to show any benefit compared with standard platinum-based CT, with a PFS (median) in the PDL1 ≥ 5% NSCLC group of 4.2 months (nivolumab) versus 5.9 months (CT; HR = 1.15: 95% CI 0.91–1.45, P = 0.25). No benefit was observed in the PDL1 ≥ 50% subgroup. An encouraging report of the efficacy of pembrolizumab in addition to CT in first-line treatment in unselected NSCLC was also presented (Keynote-021) with an ORR of 55% versus 29% with CT alone ( P = 0.0016). Atezolizumab, an anti-PDL1 antibody, showed efficacy for second-line treatment compared with docetaxel (OAK phase III study) with an OS (median) of 13.8 months versus 9.6 months with docetaxel. These results suggest a new paradigm for the treatment of advanced NSCLC using pembrolizumab for the first-line treatment of PDL1 ≥ 50% tumours.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>28407528</pmid><doi>10.1016/j.ejca.2016.12.041</doi><tpages>8</tpages></addata></record> |
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| subjects | Antibodies Antibodies, Monoclonal - therapeutic use Antibodies, Monoclonal, Humanized - therapeutic use Antineoplastic Combined Chemotherapy Protocols - therapeutic use Apoptosis Atezolizumab B7-H1 Antigen - antagonists & inhibitors Cancer Cancer therapies Carcinoma, Non-Small-Cell Lung - therapy Chemotherapy Clinical trials Clinical Trials as Topic Confidence intervals Effectiveness Hematology, Oncology and Palliative Medicine Humans Immune checkpoint inhibitor Immune checkpoint inhibitors Immune response Immunotherapy Immunotherapy - methods Inhibitor drugs Ligands Lung cancer Lung Neoplasms - therapy Monoclonal antibodies Nivolumab Non-small cell lung carcinoma Non-small-cell lung cancer PD-1 protein PD1 PDL1 Pembrolizumab Platinum Programmed Cell Death 1 Ligand 2 Protein - antagonists & inhibitors Signal transduction Subgroups Survival Targeted cancer therapy Taxoids - therapeutic use Tumors |
| title | Immunotherapy revolutionises non-small-cell lung cancer therapy: Results, perspectives and new challenges |
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