The Efficacy and Safety of PD-1/PD-L1 Inhibitors in Combination with Conventional Therapies for Advanced Solid Tumors: A Meta-Analysis
Objectives. To evaluate the efficacy of immuno-oncology combinational therapy (IOCT) versus monotherapy with programmed cell death 1 (PD-1) or PD-ligand 1 (PD-L1) inhibitors or conventional therapies, i.e., non-IOCT, in patients with advanced solid tumors. Methods. We systematically searched the Pub...
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| creator | Li, Yuan-Fang Wang, Yun Zhou, Zhi-Wei Wu, Ting Luo, Ying-Shan Xia, Xiao-Wei Zhao, Chong-Bang Nie, Run-Cong Yuan, Shu-Qiang |
| description | Objectives. To evaluate the efficacy of immuno-oncology combinational therapy (IOCT) versus monotherapy with programmed cell death 1 (PD-1) or PD-ligand 1 (PD-L1) inhibitors or conventional therapies, i.e., non-IOCT, in patients with advanced solid tumors. Methods. We systematically searched the PubMed, Embase, and Cochrane Library databases from January 2015 to October 2018 for eligible studies. We included randomized trials of IOCT with available hazard ratios (HR) for death. The random effects model was used to calculate pooled HR for death; heterogeneity was assessed using I2 statistics. The main outcome measure was overall survival (OS). Results. After screening 483 relevant articles, we identified twelve trials comprising 5388 patients for quantitative analysis. IOCT-treated patients had significantly higher tumor response rate (relative risk (RR): 2.51, 95% confidence interval (CI): 1.82-3.47), prolonged progression-free survival (HR 0.62, 95% CI: 0.53-0.74), and OS (HR 0.69, 95% CI: 0.61-0.78), compared with non-IOCT–treated patients. Sensitivity analyses also demonstrated the OS advantage of IOCT across different combination modalities, intervention agents, malignancy types, and PD-L1 expression (all P |
| doi_str_mv | 10.1155/2020/5059079 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7225910</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A629053459</galeid><sourcerecordid>A629053459</sourcerecordid><originalsourceid>FETCH-LOGICAL-c499t-7f1f5974f1b6729fa3b68ec59c72222cef61b4e87aaf8f846f1c44fc4d51df843</originalsourceid><addsrcrecordid>eNqNkU9v0zAYhyMEYtPYjTOyxJFl9es_ScwBKSpjTCoCiXK2HMdePKV2sdNO_QJ8bly1dHDDB9uv_fjRa_2K4jXgawDOZwQTPOOYC1yLZ8U5ocDKChg8P-0pPSsuU3rAeTRQYVG9LM4oYRUIwc6LX8vBoBtrnVZ6h5Tv0XdlzbRDwaJvH0uY5WkB6M4PrnNTiAk5j-Zh1TmvJhc8enTTkA_81vh9rUaUjVGtnUnIhojafqu8NtkbRtej5WaVJe9Ri76YSZVtfrBLLr0qXlg1JnN5XC-KH59ulvPP5eLr7d28XZSaCTGVtQXLRc0sdFVNhFW0qxqjudA1yUMbW0HHTFMrZRvbsMqCZsxq1nPoc00vig8H73rTrUyvc9NRjXId3UrFnQzKyX9vvBvkfdjK7OcCcBa8PQpi-LkxaZIPYRPzL5IkDNOmJkDEE3WvRiOdtyHL9MolLduKCMwp43vq6kDpGFKKxp76ACz38cp9vPIYb8bf_N37Cf4TZgbeHYDB-V49uv_UmcwYq55ooIwRSn8DL9e1tg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2403872129</pqid></control><display><type>article</type><title>The Efficacy and Safety of PD-1/PD-L1 Inhibitors in Combination with Conventional Therapies for Advanced Solid Tumors: A Meta-Analysis</title><source>MEDLINE</source><source>Wiley Online Library Open Access</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>PubMed Central Open Access</source><creator>Li, Yuan-Fang ; Wang, Yun ; Zhou, Zhi-Wei ; Wu, Ting ; Luo, Ying-Shan ; Xia, Xiao-Wei ; Zhao, Chong-Bang ; Nie, Run-Cong ; Yuan, Shu-Qiang</creator><contributor>Upham, Brad</contributor><creatorcontrib>Li, Yuan-Fang ; Wang, Yun ; Zhou, Zhi-Wei ; Wu, Ting ; Luo, Ying-Shan ; Xia, Xiao-Wei ; Zhao, Chong-Bang ; Nie, Run-Cong ; Yuan, Shu-Qiang ; Upham, Brad</creatorcontrib><description>Objectives. To evaluate the efficacy of immuno-oncology combinational therapy (IOCT) versus monotherapy with programmed cell death 1 (PD-1) or PD-ligand 1 (PD-L1) inhibitors or conventional therapies, i.e., non-IOCT, in patients with advanced solid tumors. Methods. We systematically searched the PubMed, Embase, and Cochrane Library databases from January 2015 to October 2018 for eligible studies. We included randomized trials of IOCT with available hazard ratios (HR) for death. The random effects model was used to calculate pooled HR for death; heterogeneity was assessed using I2 statistics. The main outcome measure was overall survival (OS). Results. After screening 483 relevant articles, we identified twelve trials comprising 5388 patients for quantitative analysis. IOCT-treated patients had significantly higher tumor response rate (relative risk (RR): 2.51, 95% confidence interval (CI): 1.82-3.47), prolonged progression-free survival (HR 0.62, 95% CI: 0.53-0.74), and OS (HR 0.69, 95% CI: 0.61-0.78), compared with non-IOCT–treated patients. Sensitivity analyses also demonstrated the OS advantage of IOCT across different combination modalities, intervention agents, malignancy types, and PD-L1 expression (all P<0.05). Notably, there were higher odds of high-grade (grade≥3) adverse events with IOCT (RR: 1.81, 95% CI: 1.13-2.90), but the risk of treatment-related death (RR: 1.16, 95% CI: 0.84–1.60) was not increased compared with non-IOCT. Conclusions. IOCT is a preferable treatment option over PD-1/PD-L1 inhibitor monotherapy and conventional therapy for patients with advanced solid tumors. However, we should note the increased incidence rate of high-grade AEs in IOCT.</description><identifier>ISSN: 2314-6133</identifier><identifier>EISSN: 2314-6141</identifier><identifier>DOI: 10.1155/2020/5059079</identifier><identifier>PMID: 32461994</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Publishing Corporation</publisher><subject>Analysis ; Apoptosis ; B7-H1 Antigen - antagonists & inhibitors ; Bias ; Cancer immunotherapy ; Cancer therapies ; Care and treatment ; Cell death ; Chemotherapy ; Clinical trials ; Confidence intervals ; Heterogeneity ; Humans ; Immune Checkpoint Inhibitors - adverse effects ; Immune Checkpoint Inhibitors - therapeutic use ; Immunotherapy ; Inhibitors ; Intervention ; Ipilimumab ; Malignancy ; Melanoma ; Meta-analysis ; Mortality ; Neoplasms - drug therapy ; Neoplasms - mortality ; Oncology ; PD-1 protein ; PD-L1 protein ; Programmed Cell Death 1 Receptor - antagonists & inhibitors ; Randomized Controlled Trials as Topic ; Sensitivity analysis ; Solid tumors ; Statistical analysis ; Studies ; Survival ; Tumors</subject><ispartof>BioMed research international, 2020, Vol.2020 (2020), p.1-10</ispartof><rights>Copyright © 2020 Run-Cong Nie et al.</rights><rights>COPYRIGHT 2020 John Wiley & Sons, Inc.</rights><rights>Copyright © 2020 Run-Cong Nie et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. http://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2020 Run-Cong Nie et al. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c499t-7f1f5974f1b6729fa3b68ec59c72222cef61b4e87aaf8f846f1c44fc4d51df843</citedby><cites>FETCH-LOGICAL-c499t-7f1f5974f1b6729fa3b68ec59c72222cef61b4e87aaf8f846f1c44fc4d51df843</cites><orcidid>0000-0003-3595-6304 ; 0000-0002-5836-0872 ; 0000-0003-1762-2634</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/PMC7225910/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225910/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,4010,27900,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32461994$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Upham, Brad</contributor><creatorcontrib>Li, Yuan-Fang</creatorcontrib><creatorcontrib>Wang, Yun</creatorcontrib><creatorcontrib>Zhou, Zhi-Wei</creatorcontrib><creatorcontrib>Wu, Ting</creatorcontrib><creatorcontrib>Luo, Ying-Shan</creatorcontrib><creatorcontrib>Xia, Xiao-Wei</creatorcontrib><creatorcontrib>Zhao, Chong-Bang</creatorcontrib><creatorcontrib>Nie, Run-Cong</creatorcontrib><creatorcontrib>Yuan, Shu-Qiang</creatorcontrib><title>The Efficacy and Safety of PD-1/PD-L1 Inhibitors in Combination with Conventional Therapies for Advanced Solid Tumors: A Meta-Analysis</title><title>BioMed research international</title><addtitle>Biomed Res Int</addtitle><description>Objectives. To evaluate the efficacy of immuno-oncology combinational therapy (IOCT) versus monotherapy with programmed cell death 1 (PD-1) or PD-ligand 1 (PD-L1) inhibitors or conventional therapies, i.e., non-IOCT, in patients with advanced solid tumors. Methods. We systematically searched the PubMed, Embase, and Cochrane Library databases from January 2015 to October 2018 for eligible studies. We included randomized trials of IOCT with available hazard ratios (HR) for death. The random effects model was used to calculate pooled HR for death; heterogeneity was assessed using I2 statistics. The main outcome measure was overall survival (OS). Results. After screening 483 relevant articles, we identified twelve trials comprising 5388 patients for quantitative analysis. IOCT-treated patients had significantly higher tumor response rate (relative risk (RR): 2.51, 95% confidence interval (CI): 1.82-3.47), prolonged progression-free survival (HR 0.62, 95% CI: 0.53-0.74), and OS (HR 0.69, 95% CI: 0.61-0.78), compared with non-IOCT–treated patients. Sensitivity analyses also demonstrated the OS advantage of IOCT across different combination modalities, intervention agents, malignancy types, and PD-L1 expression (all P<0.05). Notably, there were higher odds of high-grade (grade≥3) adverse events with IOCT (RR: 1.81, 95% CI: 1.13-2.90), but the risk of treatment-related death (RR: 1.16, 95% CI: 0.84–1.60) was not increased compared with non-IOCT. Conclusions. IOCT is a preferable treatment option over PD-1/PD-L1 inhibitor monotherapy and conventional therapy for patients with advanced solid tumors. However, we should note the increased incidence rate of high-grade AEs in IOCT.</description><subject>Analysis</subject><subject>Apoptosis</subject><subject>B7-H1 Antigen - antagonists & inhibitors</subject><subject>Bias</subject><subject>Cancer immunotherapy</subject><subject>Cancer therapies</subject><subject>Care and treatment</subject><subject>Cell death</subject><subject>Chemotherapy</subject><subject>Clinical trials</subject><subject>Confidence intervals</subject><subject>Heterogeneity</subject><subject>Humans</subject><subject>Immune Checkpoint Inhibitors - adverse effects</subject><subject>Immune Checkpoint Inhibitors - therapeutic use</subject><subject>Immunotherapy</subject><subject>Inhibitors</subject><subject>Intervention</subject><subject>Ipilimumab</subject><subject>Malignancy</subject><subject>Melanoma</subject><subject>Meta-analysis</subject><subject>Mortality</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - mortality</subject><subject>Oncology</subject><subject>PD-1 protein</subject><subject>PD-L1 protein</subject><subject>Programmed Cell Death 1 Receptor - antagonists & inhibitors</subject><subject>Randomized Controlled Trials as Topic</subject><subject>Sensitivity analysis</subject><subject>Solid tumors</subject><subject>Statistical analysis</subject><subject>Studies</subject><subject>Survival</subject><subject>Tumors</subject><issn>2314-6133</issn><issn>2314-6141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNkU9v0zAYhyMEYtPYjTOyxJFl9es_ScwBKSpjTCoCiXK2HMdePKV2sdNO_QJ8bly1dHDDB9uv_fjRa_2K4jXgawDOZwQTPOOYC1yLZ8U5ocDKChg8P-0pPSsuU3rAeTRQYVG9LM4oYRUIwc6LX8vBoBtrnVZ6h5Tv0XdlzbRDwaJvH0uY5WkB6M4PrnNTiAk5j-Zh1TmvJhc8enTTkA_81vh9rUaUjVGtnUnIhojafqu8NtkbRtej5WaVJe9Ri76YSZVtfrBLLr0qXlg1JnN5XC-KH59ulvPP5eLr7d28XZSaCTGVtQXLRc0sdFVNhFW0qxqjudA1yUMbW0HHTFMrZRvbsMqCZsxq1nPoc00vig8H73rTrUyvc9NRjXId3UrFnQzKyX9vvBvkfdjK7OcCcBa8PQpi-LkxaZIPYRPzL5IkDNOmJkDEE3WvRiOdtyHL9MolLduKCMwp43vq6kDpGFKKxp76ACz38cp9vPIYb8bf_N37Cf4TZgbeHYDB-V49uv_UmcwYq55ooIwRSn8DL9e1tg</recordid><startdate>2020</startdate><enddate>2020</enddate><creator>Li, Yuan-Fang</creator><creator>Wang, Yun</creator><creator>Zhou, Zhi-Wei</creator><creator>Wu, Ting</creator><creator>Luo, Ying-Shan</creator><creator>Xia, Xiao-Wei</creator><creator>Zhao, Chong-Bang</creator><creator>Nie, Run-Cong</creator><creator>Yuan, Shu-Qiang</creator><general>Hindawi Publishing Corporation</general><general>Hindawi</general><general>John Wiley & Sons, Inc</general><general>Hindawi Limited</general><scope>ADJCN</scope><scope>AHFXO</scope><scope>RHU</scope><scope>RHW</scope><scope>RHX</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>7QL</scope><scope>7QO</scope><scope>7T7</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>CWDGH</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-3595-6304</orcidid><orcidid>https://orcid.org/0000-0002-5836-0872</orcidid><orcidid>https://orcid.org/0000-0003-1762-2634</orcidid></search><sort><creationdate>2020</creationdate><title>The Efficacy and Safety of PD-1/PD-L1 Inhibitors in Combination with Conventional Therapies for Advanced Solid Tumors: A Meta-Analysis</title><author>Li, Yuan-Fang ; Wang, Yun ; Zhou, Zhi-Wei ; Wu, Ting ; Luo, Ying-Shan ; Xia, Xiao-Wei ; Zhao, Chong-Bang ; Nie, Run-Cong ; Yuan, Shu-Qiang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c499t-7f1f5974f1b6729fa3b68ec59c72222cef61b4e87aaf8f846f1c44fc4d51df843</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Analysis</topic><topic>Apoptosis</topic><topic>B7-H1 Antigen - antagonists & inhibitors</topic><topic>Bias</topic><topic>Cancer immunotherapy</topic><topic>Cancer therapies</topic><topic>Care and treatment</topic><topic>Cell death</topic><topic>Chemotherapy</topic><topic>Clinical trials</topic><topic>Confidence intervals</topic><topic>Heterogeneity</topic><topic>Humans</topic><topic>Immune Checkpoint Inhibitors - adverse effects</topic><topic>Immune Checkpoint Inhibitors - therapeutic use</topic><topic>Immunotherapy</topic><topic>Inhibitors</topic><topic>Intervention</topic><topic>Ipilimumab</topic><topic>Malignancy</topic><topic>Melanoma</topic><topic>Meta-analysis</topic><topic>Mortality</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - mortality</topic><topic>Oncology</topic><topic>PD-1 protein</topic><topic>PD-L1 protein</topic><topic>Programmed Cell Death 1 Receptor - antagonists & inhibitors</topic><topic>Randomized Controlled Trials as Topic</topic><topic>Sensitivity analysis</topic><topic>Solid tumors</topic><topic>Statistical analysis</topic><topic>Studies</topic><topic>Survival</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Yuan-Fang</creatorcontrib><creatorcontrib>Wang, Yun</creatorcontrib><creatorcontrib>Zhou, Zhi-Wei</creatorcontrib><creatorcontrib>Wu, Ting</creatorcontrib><creatorcontrib>Luo, Ying-Shan</creatorcontrib><creatorcontrib>Xia, Xiao-Wei</creatorcontrib><creatorcontrib>Zhao, Chong-Bang</creatorcontrib><creatorcontrib>Nie, Run-Cong</creatorcontrib><creatorcontrib>Yuan, Shu-Qiang</creatorcontrib><collection>الدوريات العلمية والإحصائية - 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To evaluate the efficacy of immuno-oncology combinational therapy (IOCT) versus monotherapy with programmed cell death 1 (PD-1) or PD-ligand 1 (PD-L1) inhibitors or conventional therapies, i.e., non-IOCT, in patients with advanced solid tumors. Methods. We systematically searched the PubMed, Embase, and Cochrane Library databases from January 2015 to October 2018 for eligible studies. We included randomized trials of IOCT with available hazard ratios (HR) for death. The random effects model was used to calculate pooled HR for death; heterogeneity was assessed using I2 statistics. The main outcome measure was overall survival (OS). Results. After screening 483 relevant articles, we identified twelve trials comprising 5388 patients for quantitative analysis. IOCT-treated patients had significantly higher tumor response rate (relative risk (RR): 2.51, 95% confidence interval (CI): 1.82-3.47), prolonged progression-free survival (HR 0.62, 95% CI: 0.53-0.74), and OS (HR 0.69, 95% CI: 0.61-0.78), compared with non-IOCT–treated patients. Sensitivity analyses also demonstrated the OS advantage of IOCT across different combination modalities, intervention agents, malignancy types, and PD-L1 expression (all P<0.05). Notably, there were higher odds of high-grade (grade≥3) adverse events with IOCT (RR: 1.81, 95% CI: 1.13-2.90), but the risk of treatment-related death (RR: 1.16, 95% CI: 0.84–1.60) was not increased compared with non-IOCT. Conclusions. IOCT is a preferable treatment option over PD-1/PD-L1 inhibitor monotherapy and conventional therapy for patients with advanced solid tumors. However, we should note the increased incidence rate of high-grade AEs in IOCT.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Publishing Corporation</pub><pmid>32461994</pmid><doi>10.1155/2020/5059079</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-3595-6304</orcidid><orcidid>https://orcid.org/0000-0002-5836-0872</orcidid><orcidid>https://orcid.org/0000-0003-1762-2634</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Analysis Apoptosis B7-H1 Antigen - antagonists & inhibitors Bias Cancer immunotherapy Cancer therapies Care and treatment Cell death Chemotherapy Clinical trials Confidence intervals Heterogeneity Humans Immune Checkpoint Inhibitors - adverse effects Immune Checkpoint Inhibitors - therapeutic use Immunotherapy Inhibitors Intervention Ipilimumab Malignancy Melanoma Meta-analysis Mortality Neoplasms - drug therapy Neoplasms - mortality Oncology PD-1 protein PD-L1 protein Programmed Cell Death 1 Receptor - antagonists & inhibitors Randomized Controlled Trials as Topic Sensitivity analysis Solid tumors Statistical analysis Studies Survival Tumors |
| title | The Efficacy and Safety of PD-1/PD-L1 Inhibitors in Combination with Conventional Therapies for Advanced Solid Tumors: A Meta-Analysis |
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