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Ipilimumab and nivolumab/pembrolizumab in advanced hepatocellular carcinoma refractory to prior immune checkpoint inhibitors
BackgroundProgrammed cell death protein 1 (PD-1) pathway blockade with immune checkpoint inhibitors (ICIs) is a standard therapy in advanced hepatocellular carcinoma (HCC) nowadays. No strategies to overcome ICI resistance have been described. We aimed to evaluate the use of ipilimumab and anti-PD-1...
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Published in: | Journal for immunotherapy of cancer 2021-02, Vol.9 (2), p.e001945 |
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creator | Wong, Jeffrey Sum Lung Kwok, Gerry Gin Wai Tang, Vikki Li, Bryan Cho Wing Leung, Roland Chiu, Joanne Ma, Ka Wing She, Wong Hoi Tsang, Josephine Lo, Chung Mau Cheung, Tan To Yau, Thomas |
description | BackgroundProgrammed cell death protein 1 (PD-1) pathway blockade with immune checkpoint inhibitors (ICIs) is a standard therapy in advanced hepatocellular carcinoma (HCC) nowadays. No strategies to overcome ICI resistance have been described. We aimed to evaluate the use of ipilimumab and anti-PD-1 ICIs (nivolumab or pembrolizumab) combinations in patients with advanced HCC with progression on prior ICIs.MethodsPatients with advanced HCC with documented tumor progression on prior ICIs and subsequently received ipilimumab with nivolumab/pembrolizumab were analyzed. Objective response rate (ORR), median duration of response (DOR), time-to-progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were assessed.ResultsTwenty-five patients were included. The median age was 62 (range: 51–83). About 68% were of Child-Pugh (CP) Grade A and 48% had primary resistance to prior ICI. At median follow-up of 37.7 months, the ORR was 16% with a median DOR of 11.5 months (range: 2.76–30.3). Three patients achieved complete response. The median TTP was 2.96 months (95% CI: 1.61 to 4.31). Median OS was 10.9 months (95% CI: 3.99 to 17.8) and the 1 year, 2 year and 3 year survival rates were 42.4%, 32.3% and 21.6%, respectively. The ORR was 16.7% in primary resistance group and 15.4% in acquired resistance group (p=1.00). All responders were of CP A and Albumin-Bilirubin (ALBI) Grade 1 or 2. CP and ALBI Grades were significantly associated with OS (p=0.006 and p |
doi_str_mv | 10.1136/jitc-2020-001945 |
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No strategies to overcome ICI resistance have been described. We aimed to evaluate the use of ipilimumab and anti-PD-1 ICIs (nivolumab or pembrolizumab) combinations in patients with advanced HCC with progression on prior ICIs.MethodsPatients with advanced HCC with documented tumor progression on prior ICIs and subsequently received ipilimumab with nivolumab/pembrolizumab were analyzed. Objective response rate (ORR), median duration of response (DOR), time-to-progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were assessed.ResultsTwenty-five patients were included. The median age was 62 (range: 51–83). About 68% were of Child-Pugh (CP) Grade A and 48% had primary resistance to prior ICI. At median follow-up of 37.7 months, the ORR was 16% with a median DOR of 11.5 months (range: 2.76–30.3). Three patients achieved complete response. The median TTP was 2.96 months (95% CI: 1.61 to 4.31). Median OS was 10.9 months (95% CI: 3.99 to 17.8) and the 1 year, 2 year and 3 year survival rates were 42.4%, 32.3% and 21.6%, respectively. The ORR was 16.7% in primary resistance group and 15.4% in acquired resistance group (p=1.00). All responders were of CP A and Albumin-Bilirubin (ALBI) Grade 1 or 2. CP and ALBI Grades were significantly associated with OS (p=0.006 and p<0.001, respectively). Overall, 52% of patients experienced TRAEs and 12% experienced Grade 3 or above TRAEs.ConclusionsIpilimumab and nivolumab/pembrolizumab can achieve durable antitumor activity and encouraging survival outcomes with acceptable toxicity in patients with advanced HCC who had prior treatment with ICIs.</description><identifier>ISSN: 2051-1426</identifier><identifier>EISSN: 2051-1426</identifier><identifier>DOI: 10.1136/jitc-2020-001945</identifier><identifier>PMID: 33563773</identifier><language>eng</language><publisher>England: BMJ Publishing Group LTD</publisher><subject>Aged ; Aged, 80 and over ; Antibodies ; Antibodies, Monoclonal, Humanized - adverse effects ; Antibodies, Monoclonal, Humanized - therapeutic use ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Apoptosis ; Cancer ; Cancer therapies ; Carcinoma, Hepatocellular - drug therapy ; Carcinoma, Hepatocellular - immunology ; Carcinoma, Hepatocellular - mortality ; Carcinoma, Hepatocellular - pathology ; Cell death ; Clinical/Translational Cancer Immunotherapy ; Disease Progression ; Drug Resistance, Neoplasm ; FDA approval ; Female ; Hepatitis ; Humans ; Immune Checkpoint Inhibitors - adverse effects ; Immune Checkpoint Inhibitors - therapeutic use ; Immunotherapy ; Investigations ; Ipilimumab - adverse effects ; Ipilimumab - therapeutic use ; Liver cancer ; Liver Neoplasms - drug therapy ; Liver Neoplasms - immunology ; Liver Neoplasms - mortality ; Liver Neoplasms - pathology ; Male ; Middle Aged ; Monoclonal antibodies ; Nivolumab - adverse effects ; Nivolumab - therapeutic use ; Proteins ; Regulatory approval ; Retrospective Studies ; Salvage Therapy ; Targeted cancer therapy ; Time Factors ; Treatment Outcome ; Tumor Microenvironment ; Tumors</subject><ispartof>Journal for immunotherapy of cancer, 2021-02, Vol.9 (2), p.e001945</ispartof><rights>Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.</rights><rights>2021 Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ . Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b526t-bfb6d7a05939d215478a32ed16927b6afa4ae10c8c56cf35e5d49b8dc0e88a893</citedby><cites>FETCH-LOGICAL-b526t-bfb6d7a05939d215478a32ed16927b6afa4ae10c8c56cf35e5d49b8dc0e88a893</cites><orcidid>0000-0002-2356-0831</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2552988492/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2552988492?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27549,27550,27924,27925,37012,37013,44590,53791,53793,75126,77601,77632</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33563773$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wong, Jeffrey Sum Lung</creatorcontrib><creatorcontrib>Kwok, Gerry Gin Wai</creatorcontrib><creatorcontrib>Tang, Vikki</creatorcontrib><creatorcontrib>Li, Bryan Cho Wing</creatorcontrib><creatorcontrib>Leung, Roland</creatorcontrib><creatorcontrib>Chiu, Joanne</creatorcontrib><creatorcontrib>Ma, Ka Wing</creatorcontrib><creatorcontrib>She, Wong Hoi</creatorcontrib><creatorcontrib>Tsang, Josephine</creatorcontrib><creatorcontrib>Lo, Chung Mau</creatorcontrib><creatorcontrib>Cheung, Tan To</creatorcontrib><creatorcontrib>Yau, Thomas</creatorcontrib><title>Ipilimumab and nivolumab/pembrolizumab in advanced hepatocellular carcinoma refractory to prior immune checkpoint inhibitors</title><title>Journal for immunotherapy of cancer</title><addtitle>J Immunother Cancer</addtitle><description>BackgroundProgrammed cell death protein 1 (PD-1) pathway blockade with immune checkpoint inhibitors (ICIs) is a standard therapy in advanced hepatocellular carcinoma (HCC) nowadays. No strategies to overcome ICI resistance have been described. We aimed to evaluate the use of ipilimumab and anti-PD-1 ICIs (nivolumab or pembrolizumab) combinations in patients with advanced HCC with progression on prior ICIs.MethodsPatients with advanced HCC with documented tumor progression on prior ICIs and subsequently received ipilimumab with nivolumab/pembrolizumab were analyzed. Objective response rate (ORR), median duration of response (DOR), time-to-progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were assessed.ResultsTwenty-five patients were included. The median age was 62 (range: 51–83). About 68% were of Child-Pugh (CP) Grade A and 48% had primary resistance to prior ICI. At median follow-up of 37.7 months, the ORR was 16% with a median DOR of 11.5 months (range: 2.76–30.3). Three patients achieved complete response. The median TTP was 2.96 months (95% CI: 1.61 to 4.31). Median OS was 10.9 months (95% CI: 3.99 to 17.8) and the 1 year, 2 year and 3 year survival rates were 42.4%, 32.3% and 21.6%, respectively. The ORR was 16.7% in primary resistance group and 15.4% in acquired resistance group (p=1.00). All responders were of CP A and Albumin-Bilirubin (ALBI) Grade 1 or 2. CP and ALBI Grades were significantly associated with OS (p=0.006 and p<0.001, respectively). Overall, 52% of patients experienced TRAEs and 12% experienced Grade 3 or above TRAEs.ConclusionsIpilimumab and nivolumab/pembrolizumab can achieve durable antitumor activity and encouraging survival outcomes with acceptable toxicity in patients with advanced HCC who had prior treatment with ICIs.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antibodies</subject><subject>Antibodies, Monoclonal, Humanized - adverse effects</subject><subject>Antibodies, Monoclonal, Humanized - therapeutic use</subject><subject>Antineoplastic Combined Chemotherapy Protocols - adverse effects</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Apoptosis</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Carcinoma, Hepatocellular - drug therapy</subject><subject>Carcinoma, Hepatocellular - immunology</subject><subject>Carcinoma, Hepatocellular - mortality</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Cell death</subject><subject>Clinical/Translational Cancer Immunotherapy</subject><subject>Disease Progression</subject><subject>Drug Resistance, Neoplasm</subject><subject>FDA approval</subject><subject>Female</subject><subject>Hepatitis</subject><subject>Humans</subject><subject>Immune Checkpoint Inhibitors - adverse effects</subject><subject>Immune Checkpoint Inhibitors - therapeutic use</subject><subject>Immunotherapy</subject><subject>Investigations</subject><subject>Ipilimumab - adverse effects</subject><subject>Ipilimumab - therapeutic use</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - drug therapy</subject><subject>Liver Neoplasms - immunology</subject><subject>Liver Neoplasms - mortality</subject><subject>Liver Neoplasms - pathology</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Monoclonal antibodies</subject><subject>Nivolumab - adverse effects</subject><subject>Nivolumab - therapeutic use</subject><subject>Proteins</subject><subject>Regulatory approval</subject><subject>Retrospective Studies</subject><subject>Salvage Therapy</subject><subject>Targeted cancer therapy</subject><subject>Time Factors</subject><subject>Treatment Outcome</subject><subject>Tumor Microenvironment</subject><subject>Tumors</subject><issn>2051-1426</issn><issn>2051-1426</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>9YT</sourceid><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqFkstr1UAUh4Motly7dyUBN4LEzjMz2QhStL1QcKPr4cwjvROTmThJLlT84500tbRuXM3rm48zZ35F8RqjDxjT-rzzs6kIIqhCCDeMPytOCeK4wozUzx_NT4qzaepQhhClUsqXxQmlvKZC0NPi9370vR-WAXQJwZbBH2O_rs5HN-gUe__r7syHEuwRgnG2PLgR5mhc3y89pNJAMj7EAcrk2gRmjum2nGM5Jh9T6YdhCa40B2d-jNGHOasOXvtMTa-KFy30kzu7H3fF9y-fv11cVddfL_cXn64rzUk9V7rVtRWAeEMbSzBnQgIlzuK6IULX0AIDh5GRhtempdxxyxotrUFOSpAN3RX7zWsjdCrXNUC6VRG8utuI6UZBmr3pneKtFFZrRgnNLSVUcuyYpkzXDactg-z6uLnGRQ_OGhfmBP0T6dOT4A_qJh6VkIKTLNkV7-4FKf5c3DSrwU9rMyG4uEyKMCmxFFiQjL79B-3ikkJulSI8y6RkzUqhjTIpTlP-g4diMFJrUtSaFLUmRW1JyVfePH7Ew4W_ucjA-w3QQ_d_3R_P08qX</recordid><startdate>202102</startdate><enddate>202102</enddate><creator>Wong, Jeffrey Sum Lung</creator><creator>Kwok, Gerry Gin Wai</creator><creator>Tang, Vikki</creator><creator>Li, Bryan Cho Wing</creator><creator>Leung, Roland</creator><creator>Chiu, Joanne</creator><creator>Ma, Ka Wing</creator><creator>She, Wong Hoi</creator><creator>Tsang, Josephine</creator><creator>Lo, Chung Mau</creator><creator>Cheung, Tan To</creator><creator>Yau, Thomas</creator><general>BMJ Publishing Group LTD</general><general>BMJ Publishing Group</general><scope>9YT</scope><scope>ACMMV</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>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</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/0000-0002-2356-0831</orcidid></search><sort><creationdate>202102</creationdate><title>Ipilimumab and nivolumab/pembrolizumab in advanced hepatocellular carcinoma refractory to prior immune checkpoint inhibitors</title><author>Wong, Jeffrey Sum Lung ; Kwok, Gerry Gin Wai ; Tang, Vikki ; Li, Bryan Cho Wing ; Leung, Roland ; Chiu, Joanne ; Ma, Ka Wing ; She, Wong Hoi ; Tsang, Josephine ; Lo, Chung Mau ; Cheung, Tan To ; Yau, Thomas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b526t-bfb6d7a05939d215478a32ed16927b6afa4ae10c8c56cf35e5d49b8dc0e88a893</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antibodies</topic><topic>Antibodies, Monoclonal, Humanized - 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therapeutic use</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - drug therapy</topic><topic>Liver Neoplasms - immunology</topic><topic>Liver Neoplasms - mortality</topic><topic>Liver Neoplasms - pathology</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Monoclonal antibodies</topic><topic>Nivolumab - adverse effects</topic><topic>Nivolumab - therapeutic use</topic><topic>Proteins</topic><topic>Regulatory approval</topic><topic>Retrospective Studies</topic><topic>Salvage Therapy</topic><topic>Targeted cancer therapy</topic><topic>Time Factors</topic><topic>Treatment Outcome</topic><topic>Tumor Microenvironment</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wong, Jeffrey Sum Lung</creatorcontrib><creatorcontrib>Kwok, Gerry Gin Wai</creatorcontrib><creatorcontrib>Tang, Vikki</creatorcontrib><creatorcontrib>Li, Bryan Cho Wing</creatorcontrib><creatorcontrib>Leung, Roland</creatorcontrib><creatorcontrib>Chiu, Joanne</creatorcontrib><creatorcontrib>Ma, Ka Wing</creatorcontrib><creatorcontrib>She, Wong Hoi</creatorcontrib><creatorcontrib>Tsang, Josephine</creatorcontrib><creatorcontrib>Lo, Chung Mau</creatorcontrib><creatorcontrib>Cheung, Tan To</creatorcontrib><creatorcontrib>Yau, Thomas</creatorcontrib><collection>BMJ Open Access Journals</collection><collection>BMJ Journals: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>Medical Database (Alumni Edition)</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>ProQuest Central</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 Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Publicly Available Content Database</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(OpenAccess)</collection><jtitle>Journal for immunotherapy of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wong, Jeffrey Sum Lung</au><au>Kwok, Gerry Gin Wai</au><au>Tang, Vikki</au><au>Li, Bryan Cho Wing</au><au>Leung, Roland</au><au>Chiu, Joanne</au><au>Ma, Ka Wing</au><au>She, Wong Hoi</au><au>Tsang, Josephine</au><au>Lo, Chung Mau</au><au>Cheung, Tan To</au><au>Yau, Thomas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ipilimumab and nivolumab/pembrolizumab in advanced hepatocellular carcinoma refractory to prior immune checkpoint inhibitors</atitle><jtitle>Journal for immunotherapy of cancer</jtitle><addtitle>J Immunother Cancer</addtitle><date>2021-02</date><risdate>2021</risdate><volume>9</volume><issue>2</issue><spage>e001945</spage><pages>e001945-</pages><issn>2051-1426</issn><eissn>2051-1426</eissn><abstract>BackgroundProgrammed cell death protein 1 (PD-1) pathway blockade with immune checkpoint inhibitors (ICIs) is a standard therapy in advanced hepatocellular carcinoma (HCC) nowadays. No strategies to overcome ICI resistance have been described. We aimed to evaluate the use of ipilimumab and anti-PD-1 ICIs (nivolumab or pembrolizumab) combinations in patients with advanced HCC with progression on prior ICIs.MethodsPatients with advanced HCC with documented tumor progression on prior ICIs and subsequently received ipilimumab with nivolumab/pembrolizumab were analyzed. Objective response rate (ORR), median duration of response (DOR), time-to-progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were assessed.ResultsTwenty-five patients were included. The median age was 62 (range: 51–83). About 68% were of Child-Pugh (CP) Grade A and 48% had primary resistance to prior ICI. At median follow-up of 37.7 months, the ORR was 16% with a median DOR of 11.5 months (range: 2.76–30.3). Three patients achieved complete response. The median TTP was 2.96 months (95% CI: 1.61 to 4.31). Median OS was 10.9 months (95% CI: 3.99 to 17.8) and the 1 year, 2 year and 3 year survival rates were 42.4%, 32.3% and 21.6%, respectively. The ORR was 16.7% in primary resistance group and 15.4% in acquired resistance group (p=1.00). All responders were of CP A and Albumin-Bilirubin (ALBI) Grade 1 or 2. CP and ALBI Grades were significantly associated with OS (p=0.006 and p<0.001, respectively). Overall, 52% of patients experienced TRAEs and 12% experienced Grade 3 or above TRAEs.ConclusionsIpilimumab and nivolumab/pembrolizumab can achieve durable antitumor activity and encouraging survival outcomes with acceptable toxicity in patients with advanced HCC who had prior treatment with ICIs.</abstract><cop>England</cop><pub>BMJ Publishing Group LTD</pub><pmid>33563773</pmid><doi>10.1136/jitc-2020-001945</doi><orcidid>https://orcid.org/0000-0002-2356-0831</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Aged Aged, 80 and over Antibodies Antibodies, Monoclonal, Humanized - adverse effects Antibodies, Monoclonal, Humanized - therapeutic use Antineoplastic Combined Chemotherapy Protocols - adverse effects Antineoplastic Combined Chemotherapy Protocols - therapeutic use Apoptosis Cancer Cancer therapies Carcinoma, Hepatocellular - drug therapy Carcinoma, Hepatocellular - immunology Carcinoma, Hepatocellular - mortality Carcinoma, Hepatocellular - pathology Cell death Clinical/Translational Cancer Immunotherapy Disease Progression Drug Resistance, Neoplasm FDA approval Female Hepatitis Humans Immune Checkpoint Inhibitors - adverse effects Immune Checkpoint Inhibitors - therapeutic use Immunotherapy Investigations Ipilimumab - adverse effects Ipilimumab - therapeutic use Liver cancer Liver Neoplasms - drug therapy Liver Neoplasms - immunology Liver Neoplasms - mortality Liver Neoplasms - pathology Male Middle Aged Monoclonal antibodies Nivolumab - adverse effects Nivolumab - therapeutic use Proteins Regulatory approval Retrospective Studies Salvage Therapy Targeted cancer therapy Time Factors Treatment Outcome Tumor Microenvironment Tumors |
title | Ipilimumab and nivolumab/pembrolizumab in advanced hepatocellular carcinoma refractory to prior immune checkpoint inhibitors |
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