Potential predictors for survival in hepatocellular carcinoma patients treated with immune checkpoint inhibitors: A meta-analysis
•Combination regimen provides superior efficacy than immune checkpoint inhibitor monotherapy.•As an early surrogate, DCR is significantly correlated with PFS and OS.•The correlation between PFS and OS is more significant in combination groups. Immune checkpoint inhibitors (ICI) are increasingly used...
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| Veröffentlicht in: | International immunopharmacology 2021-11, Vol.100, p.108135-108135, Article 108135 |
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| creator | Xu, Huilin Cao, Dedong Zheng, Yongfa Zhou, Dingjie Chen, Xin Lei, Jinju Ge, Wei Xu, Ximing |
| description | •Combination regimen provides superior efficacy than immune checkpoint inhibitor monotherapy.•As an early surrogate, DCR is significantly correlated with PFS and OS.•The correlation between PFS and OS is more significant in combination groups.
Immune checkpoint inhibitors (ICI) are increasingly used in hepatocellular carcinoma (HCC) trials. However, the correlations between early endpoints, such as progression free survival (PFS), objective response rate (ORR), and disease control rate (DCR), and overall survival (OS) are unclear. In this study, the correlations between OS and other early endpoints were evaluated in HCC patients who received ICI.
Pubmed and Embase were searched to October 2020. Clinical studies evaluating efficacy and outcomes of HCC patients treated with ICI were included. ORR, DCR, PFS and OS were extracted from individual studies. The Spearman's rank correlation coefficient and linear regression model were used to assess the correlation.
74 studies involving 9001 HCC cases were included. For HCC patients treated with ICI, the pooled ORR and DCR were 16% (95% CI: 14–18%) and 52% (95% CI: 47–57%), and the median PFS and OS were 3.75 (95% CI: 2.88–4.90) months, and 13.20 (95% CI: 11.88–14.82) months, retrospectively. The correlation between ORR, DCR, PFS and OS were 0.35 (R2 = 0.21, p |
| doi_str_mv | 10.1016/j.intimp.2021.108135 |
| format | Article |
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Immune checkpoint inhibitors (ICI) are increasingly used in hepatocellular carcinoma (HCC) trials. However, the correlations between early endpoints, such as progression free survival (PFS), objective response rate (ORR), and disease control rate (DCR), and overall survival (OS) are unclear. In this study, the correlations between OS and other early endpoints were evaluated in HCC patients who received ICI.
Pubmed and Embase were searched to October 2020. Clinical studies evaluating efficacy and outcomes of HCC patients treated with ICI were included. ORR, DCR, PFS and OS were extracted from individual studies. The Spearman's rank correlation coefficient and linear regression model were used to assess the correlation.
74 studies involving 9001 HCC cases were included. For HCC patients treated with ICI, the pooled ORR and DCR were 16% (95% CI: 14–18%) and 52% (95% CI: 47–57%), and the median PFS and OS were 3.75 (95% CI: 2.88–4.90) months, and 13.20 (95% CI: 11.88–14.82) months, retrospectively. The correlation between ORR, DCR, PFS and OS were 0.35 (R2 = 0.21, p < 0.05), 0.43 (R2 = 0.18, p < 0.05), and 0.50 (R2 = 0.33, p < 0.05), respectively. Further, the association between PFS and OS of the combination strategy showed a better correlation (rs = 0.79, R2 = 0.75, p < 0.05).
These results suggest that PFS could be potential surrogates for OS, especially PFS for patients who treated with ICI combination regimen.</description><identifier>ISSN: 1567-5769</identifier><identifier>EISSN: 1878-1705</identifier><identifier>DOI: 10.1016/j.intimp.2021.108135</identifier><identifier>PMID: 34530205</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Carcinoma, Hepatocellular - drug therapy ; Carcinoma, Hepatocellular - immunology ; Carcinoma, Hepatocellular - mortality ; Clinical trials ; Correlation coefficient ; Correlation coefficients ; Disease control ; Disease control rate ; Evaluation ; Female ; Hepatocellular carcinoma ; Humans ; Immune checkpoint inhibitor ; Immune checkpoint inhibitors ; Immune Checkpoint Inhibitors - adverse effects ; Immune Checkpoint Inhibitors - therapeutic use ; Inhibitors ; Liver cancer ; Liver Neoplasms - drug therapy ; Liver Neoplasms - immunology ; Liver Neoplasms - mortality ; Male ; Meta-analysis ; Middle Aged ; Overall survival ; Patients ; Progression free survival ; Regression models ; Survival ; Time Factors</subject><ispartof>International immunopharmacology, 2021-11, Vol.100, p.108135-108135, Article 108135</ispartof><rights>2021</rights><rights>Copyright © 2021. Published by Elsevier B.V.</rights><rights>Copyright Elsevier BV Nov 2021</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-2e43d6ee37d6d5cfb06b96dbdade5f450aecac13f820233ee3c188687648ba493</citedby><cites>FETCH-LOGICAL-c390t-2e43d6ee37d6d5cfb06b96dbdade5f450aecac13f820233ee3c188687648ba493</cites><orcidid>0000-0002-5777-4176 ; 0000-0001-5905-575X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1567576921007712$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34530205$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xu, Huilin</creatorcontrib><creatorcontrib>Cao, Dedong</creatorcontrib><creatorcontrib>Zheng, Yongfa</creatorcontrib><creatorcontrib>Zhou, Dingjie</creatorcontrib><creatorcontrib>Chen, Xin</creatorcontrib><creatorcontrib>Lei, Jinju</creatorcontrib><creatorcontrib>Ge, Wei</creatorcontrib><creatorcontrib>Xu, Ximing</creatorcontrib><title>Potential predictors for survival in hepatocellular carcinoma patients treated with immune checkpoint inhibitors: A meta-analysis</title><title>International immunopharmacology</title><addtitle>Int Immunopharmacol</addtitle><description>•Combination regimen provides superior efficacy than immune checkpoint inhibitor monotherapy.•As an early surrogate, DCR is significantly correlated with PFS and OS.•The correlation between PFS and OS is more significant in combination groups.
Immune checkpoint inhibitors (ICI) are increasingly used in hepatocellular carcinoma (HCC) trials. However, the correlations between early endpoints, such as progression free survival (PFS), objective response rate (ORR), and disease control rate (DCR), and overall survival (OS) are unclear. In this study, the correlations between OS and other early endpoints were evaluated in HCC patients who received ICI.
Pubmed and Embase were searched to October 2020. Clinical studies evaluating efficacy and outcomes of HCC patients treated with ICI were included. ORR, DCR, PFS and OS were extracted from individual studies. The Spearman's rank correlation coefficient and linear regression model were used to assess the correlation.
74 studies involving 9001 HCC cases were included. For HCC patients treated with ICI, the pooled ORR and DCR were 16% (95% CI: 14–18%) and 52% (95% CI: 47–57%), and the median PFS and OS were 3.75 (95% CI: 2.88–4.90) months, and 13.20 (95% CI: 11.88–14.82) months, retrospectively. The correlation between ORR, DCR, PFS and OS were 0.35 (R2 = 0.21, p < 0.05), 0.43 (R2 = 0.18, p < 0.05), and 0.50 (R2 = 0.33, p < 0.05), respectively. Further, the association between PFS and OS of the combination strategy showed a better correlation (rs = 0.79, R2 = 0.75, p < 0.05).
These results suggest that PFS could be potential surrogates for OS, especially PFS for patients who treated with ICI combination regimen.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antineoplastic Combined Chemotherapy Protocols - adverse effects</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Carcinoma, Hepatocellular - drug therapy</subject><subject>Carcinoma, Hepatocellular - immunology</subject><subject>Carcinoma, Hepatocellular - mortality</subject><subject>Clinical trials</subject><subject>Correlation coefficient</subject><subject>Correlation coefficients</subject><subject>Disease control</subject><subject>Disease control rate</subject><subject>Evaluation</subject><subject>Female</subject><subject>Hepatocellular carcinoma</subject><subject>Humans</subject><subject>Immune checkpoint inhibitor</subject><subject>Immune checkpoint inhibitors</subject><subject>Immune Checkpoint Inhibitors - adverse effects</subject><subject>Immune Checkpoint Inhibitors - therapeutic use</subject><subject>Inhibitors</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - drug therapy</subject><subject>Liver Neoplasms - immunology</subject><subject>Liver Neoplasms - mortality</subject><subject>Male</subject><subject>Meta-analysis</subject><subject>Middle Aged</subject><subject>Overall survival</subject><subject>Patients</subject><subject>Progression free survival</subject><subject>Regression models</subject><subject>Survival</subject><subject>Time Factors</subject><issn>1567-5769</issn><issn>1878-1705</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUtv1DAUhS0EoqXwDxCyxIZNBjt-JGGBVFW8pErtAtaWY99oPCRxsJ1BXfaf945SWLBgZevou8fX5xDymrMdZ1y_P-zCXMK07GpWc5RaLtQTcs7bpq14w9RTvCvdVKrR3Rl5kfOBMdQlf07OhFSC1Uydk_vbWAB97EiXBD64ElOmQ0w0r-kYjqiHme5hsSU6GMd1tIk6m1yY42QpygHHMy0JbAFPf4eyp2Ga1hmo24P7uURcEz32oQ8n7w_0kk5QbGVnO97lkF-SZ4MdM7x6PC_Ij8-fvl99ra5vvny7uryunOhYqWqQwmsA0XjtlRt6pvtO-95bD2qQillw1nExtJiHEAg63ra6bbRseys7cUHebb5Lir9WyMVMIZ--ZGeIaza1aqTEeDRD9O0_6CGuCfdFSjOMTnW8RkpulEsx5wSDWVKYbLoznJlTReZgtorMqSKzVYRjbx7N134C_3foTycIfNwAwDSOAZLJDkN22E4CV4yP4f8vPAAEZKch</recordid><startdate>202111</startdate><enddate>202111</enddate><creator>Xu, Huilin</creator><creator>Cao, Dedong</creator><creator>Zheng, Yongfa</creator><creator>Zhou, Dingjie</creator><creator>Chen, Xin</creator><creator>Lei, Jinju</creator><creator>Ge, Wei</creator><creator>Xu, Ximing</creator><general>Elsevier B.V</general><general>Elsevier BV</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>7QO</scope><scope>7T5</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-5777-4176</orcidid><orcidid>https://orcid.org/0000-0001-5905-575X</orcidid></search><sort><creationdate>202111</creationdate><title>Potential predictors for survival in hepatocellular carcinoma patients treated with immune checkpoint inhibitors: A meta-analysis</title><author>Xu, Huilin ; Cao, Dedong ; Zheng, Yongfa ; Zhou, Dingjie ; Chen, Xin ; Lei, Jinju ; Ge, Wei ; Xu, Ximing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-2e43d6ee37d6d5cfb06b96dbdade5f450aecac13f820233ee3c188687648ba493</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antineoplastic Combined Chemotherapy Protocols - adverse effects</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Carcinoma, Hepatocellular - drug therapy</topic><topic>Carcinoma, Hepatocellular - immunology</topic><topic>Carcinoma, Hepatocellular - mortality</topic><topic>Clinical trials</topic><topic>Correlation coefficient</topic><topic>Correlation coefficients</topic><topic>Disease control</topic><topic>Disease control rate</topic><topic>Evaluation</topic><topic>Female</topic><topic>Hepatocellular carcinoma</topic><topic>Humans</topic><topic>Immune checkpoint inhibitor</topic><topic>Immune checkpoint inhibitors</topic><topic>Immune Checkpoint Inhibitors - adverse effects</topic><topic>Immune Checkpoint Inhibitors - therapeutic use</topic><topic>Inhibitors</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - drug therapy</topic><topic>Liver Neoplasms - immunology</topic><topic>Liver Neoplasms - mortality</topic><topic>Male</topic><topic>Meta-analysis</topic><topic>Middle Aged</topic><topic>Overall survival</topic><topic>Patients</topic><topic>Progression free survival</topic><topic>Regression models</topic><topic>Survival</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xu, Huilin</creatorcontrib><creatorcontrib>Cao, Dedong</creatorcontrib><creatorcontrib>Zheng, Yongfa</creatorcontrib><creatorcontrib>Zhou, Dingjie</creatorcontrib><creatorcontrib>Chen, Xin</creatorcontrib><creatorcontrib>Lei, Jinju</creatorcontrib><creatorcontrib>Ge, Wei</creatorcontrib><creatorcontrib>Xu, Ximing</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>International immunopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xu, Huilin</au><au>Cao, Dedong</au><au>Zheng, Yongfa</au><au>Zhou, Dingjie</au><au>Chen, Xin</au><au>Lei, Jinju</au><au>Ge, Wei</au><au>Xu, Ximing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Potential predictors for survival in hepatocellular carcinoma patients treated with immune checkpoint inhibitors: A meta-analysis</atitle><jtitle>International immunopharmacology</jtitle><addtitle>Int Immunopharmacol</addtitle><date>2021-11</date><risdate>2021</risdate><volume>100</volume><spage>108135</spage><epage>108135</epage><pages>108135-108135</pages><artnum>108135</artnum><issn>1567-5769</issn><eissn>1878-1705</eissn><abstract>•Combination regimen provides superior efficacy than immune checkpoint inhibitor monotherapy.•As an early surrogate, DCR is significantly correlated with PFS and OS.•The correlation between PFS and OS is more significant in combination groups.
Immune checkpoint inhibitors (ICI) are increasingly used in hepatocellular carcinoma (HCC) trials. However, the correlations between early endpoints, such as progression free survival (PFS), objective response rate (ORR), and disease control rate (DCR), and overall survival (OS) are unclear. In this study, the correlations between OS and other early endpoints were evaluated in HCC patients who received ICI.
Pubmed and Embase were searched to October 2020. Clinical studies evaluating efficacy and outcomes of HCC patients treated with ICI were included. ORR, DCR, PFS and OS were extracted from individual studies. The Spearman's rank correlation coefficient and linear regression model were used to assess the correlation.
74 studies involving 9001 HCC cases were included. For HCC patients treated with ICI, the pooled ORR and DCR were 16% (95% CI: 14–18%) and 52% (95% CI: 47–57%), and the median PFS and OS were 3.75 (95% CI: 2.88–4.90) months, and 13.20 (95% CI: 11.88–14.82) months, retrospectively. The correlation between ORR, DCR, PFS and OS were 0.35 (R2 = 0.21, p < 0.05), 0.43 (R2 = 0.18, p < 0.05), and 0.50 (R2 = 0.33, p < 0.05), respectively. Further, the association between PFS and OS of the combination strategy showed a better correlation (rs = 0.79, R2 = 0.75, p < 0.05).
These results suggest that PFS could be potential surrogates for OS, especially PFS for patients who treated with ICI combination regimen.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>34530205</pmid><doi>10.1016/j.intimp.2021.108135</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-5777-4176</orcidid><orcidid>https://orcid.org/0000-0001-5905-575X</orcidid></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Antineoplastic Combined Chemotherapy Protocols - adverse effects Antineoplastic Combined Chemotherapy Protocols - therapeutic use Carcinoma, Hepatocellular - drug therapy Carcinoma, Hepatocellular - immunology Carcinoma, Hepatocellular - mortality Clinical trials Correlation coefficient Correlation coefficients Disease control Disease control rate Evaluation Female Hepatocellular carcinoma Humans Immune checkpoint inhibitor Immune checkpoint inhibitors Immune Checkpoint Inhibitors - adverse effects Immune Checkpoint Inhibitors - therapeutic use Inhibitors Liver cancer Liver Neoplasms - drug therapy Liver Neoplasms - immunology Liver Neoplasms - mortality Male Meta-analysis Middle Aged Overall survival Patients Progression free survival Regression models Survival Time Factors |
| title | Potential predictors for survival in hepatocellular carcinoma patients treated with immune checkpoint inhibitors: A meta-analysis |
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