Adverse Events of Concurrent Immune Checkpoint Inhibitors and Antiangiogenic Agents: A Systematic Review
Identifieur interne : 000A28 ( Pmc/Checkpoint ); précédent : 000A27; suivant : 000A29Adverse Events of Concurrent Immune Checkpoint Inhibitors and Antiangiogenic Agents: A Systematic Review
Auteurs : Ling Gao ; Xi Yang ; Cheng Yi ; Hong ZhuSource :
- Frontiers in Pharmacology [ 1663-9812 ] ; 2019.
Abstract
Url:
DOI: 10.3389/fphar.2019.01173
PubMed: 31680957
PubMed Central: 6812341
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Adverse Events of Concurrent Immune Checkpoint Inhibitors and Antiangiogenic Agents: A Systematic Review</title><author><name sortKey="Gao, Ling" sort="Gao, Ling" uniqKey="Gao L" first="Ling" last="Gao">Ling Gao</name></author><author><name sortKey="Yang, Xi" sort="Yang, Xi" uniqKey="Yang X" first="Xi" last="Yang">Xi Yang</name></author><author><name sortKey="Yi, Cheng" sort="Yi, Cheng" uniqKey="Yi C" first="Cheng" last="Yi">Cheng Yi</name></author><author><name sortKey="Zhu, Hong" sort="Zhu, Hong" uniqKey="Zhu H" first="Hong" last="Zhu">Hong Zhu</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31680957</idno><idno type="pmc">6812341</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6812341</idno><idno type="RBID">PMC:6812341</idno><idno type="doi">10.3389/fphar.2019.01173</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000B22</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000B22</idno><idno type="wicri:Area/Pmc/Curation">000B22</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000B22</idno><idno type="wicri:Area/Pmc/Checkpoint">000A28</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000A28</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Adverse Events of Concurrent Immune Checkpoint Inhibitors and Antiangiogenic Agents: A Systematic Review</title><author><name sortKey="Gao, Ling" sort="Gao, Ling" uniqKey="Gao L" first="Ling" last="Gao">Ling Gao</name></author><author><name sortKey="Yang, Xi" sort="Yang, Xi" uniqKey="Yang X" first="Xi" last="Yang">Xi Yang</name></author><author><name sortKey="Yi, Cheng" sort="Yi, Cheng" uniqKey="Yi C" first="Cheng" last="Yi">Cheng Yi</name></author><author><name sortKey="Zhu, Hong" sort="Zhu, Hong" uniqKey="Zhu H" first="Hong" last="Zhu">Hong Zhu</name></author></analytic><series><title level="j">Frontiers in Pharmacology</title><idno type="eISSN">1663-9812</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><bold>Background:</bold> Immune checkpoint blockade has revolutionized the treatment of multiple malignancies. Currently, however, the effect is not universal, with objective response rates (ORR) of about 15–25%, and even lower for some cancers. Abnormal vasculature is a hallmark of most solid tumors and plays a role in immune evasion. Growing body of evidence suggests that vascular normalization and immune reprogramming could operate synergistic effect, resulting in an enhanced therapeutic efficacy. However, the benefit of antitumor efficacy must be weighed against the risk of added toxicity. In this systematic review, we summarize severe toxicity observed in such a kind of combination regimen.</p><p><bold>Methods:</bold> PubMed and Embase were searched for English references published up to May 31, 2019, with MeSH and keywords search terms of immune checkpoint inhibitors (ICIs) and antiangiogenic agents approved for using in solid tumors. Studies performing concomitant use of ICIs and antiangiogenic agents, and also reporting severe treatment-related adverse events (trAEs) (≥grade 3), were included for further analysis.</p><p><bold>Results:</bold> A total of 32 studies including a total of 2,324 participants were analyzed. Limited available data suggests that both antiangiogenic monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs) show potential risk of increasing treatment-related toxicity when combined with ICIs. Overall, the total incidence of severe adverse events (AEs) associated with ICIs plus mAbs (44.5%) is lower than that of ICIs plus TKIs (60.1%). However, the trAEs observed in combination therapy are mostly consistent with the known safety profiles of corresponding monotherapy, and they seem to be largely related to antiangiogenic agents, rather than a true immune-related adverse event (irAE) predominantly due to ICIs. The majority of trAEs are intervened by holding ICI treatment and adding corticosteroids, as well as reducing dose or adjusting administration frequency of the antiangiogenic drugs.</p><p><bold>Conclusions:</bold> Concurrent use of ICIs and antiangiogenic agents shows potential treatment-related toxicity. Further research is required to compare the efficacy and safety of the combination regimen and corresponding monotherapy and identify predictive biomarkers, as well as explore dose, duration, and sequencing schedules of drugs.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Allen, E" uniqKey="Allen E">E. Allen</name></author><author><name sortKey="Jabouille, A" uniqKey="Jabouille A">A. Jabouille</name></author><author><name sortKey="Rivera, L B" uniqKey="Rivera L">L. B. Rivera</name></author><author><name sortKey="Lodewijckx, I" uniqKey="Lodewijckx I">I. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Front Pharmacol</journal-id><journal-id journal-id-type="iso-abbrev">Front Pharmacol</journal-id><journal-id journal-id-type="publisher-id">Front. Pharmacol.</journal-id><journal-title-group><journal-title>Frontiers in Pharmacology</journal-title></journal-title-group><issn pub-type="epub">1663-9812</issn><publisher><publisher-name>Frontiers Media S.A.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31680957</article-id><article-id pub-id-type="pmc">6812341</article-id><article-id pub-id-type="doi">10.3389/fphar.2019.01173</article-id><article-categories><subj-group subj-group-type="heading"><subject>Pharmacology</subject><subj-group><subject>Systematic Review</subject></subj-group></subj-group></article-categories><title-group><article-title>Adverse Events of Concurrent Immune Checkpoint Inhibitors and Antiangiogenic Agents: A Systematic Review</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Gao</surname><given-names>Ling</given-names></name><xref ref-type="author-notes" rid="fn003"><sup>†</sup></xref><uri xlink:type="simple" xlink:href="https://loop.frontiersin.org/people/561828"></uri></contrib><contrib contrib-type="author"><name><surname>Yang</surname><given-names>Xi</given-names></name><xref ref-type="author-notes" rid="fn003"><sup>†</sup></xref></contrib><contrib contrib-type="author"><name><surname>Yi</surname><given-names>Cheng</given-names></name><xref ref-type="author-notes" rid="fn001"><sup>*</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zhu</surname><given-names>Hong</given-names></name><xref ref-type="author-notes" rid="fn001"><sup>*</sup></xref></contrib></contrib-group><aff id="aff1"><institution>Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University</institution>,<addr-line>Chengdu</addr-line>,<country>China</country></aff><author-notes><fn fn-type="edited-by"><p>Edited by: Shuang Zhou, University of Houston, United States</p></fn><fn fn-type="edited-by"><p>Reviewed by: Feng Tian, Harvard Medical School, United States; Robert L. Lins, Retired, Antwerp, Belgium</p></fn><corresp id="fn001">*Correspondence: Cheng Yi, <email xlink:href="mailto:yicheng6834@163.com" xlink:type="simple">yicheng6834@163.com</email>; Hong Zhu, <email xlink:href="mailto:441695131@qq.com" xlink:type="simple">441695131@qq.com</email></corresp><fn fn-type="other" id="fn002"><p>This article was submitted to Pharmaceutical Medicine and Outcomes Research, a section of the journal Frontiers in Pharmacology</p></fn><fn fn-type="equal" id="fn003"><p>†These authors have contributed equally to this work</p></fn></author-notes><pub-date pub-type="epub"><day>17</day><month>10</month><year>2019</year></pub-date><pub-date pub-type="collection"><year>2019</year></pub-date><volume>10</volume><elocation-id>1173</elocation-id><history><date date-type="received"><day>30</day><month>6</month><year>2019</year></date><date date-type="accepted"><day>12</day><month>9</month><year>2019</year></date></history><permissions><copyright-statement>Copyright © 2019 Gao, Yang, Yi and Zhu</copyright-statement><copyright-year>2019</copyright-year><copyright-holder>Gao, Yang, Yi and Zhu</copyright-holder><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p></license></permissions><abstract><p><bold>Background:</bold> Immune checkpoint blockade has revolutionized the treatment of multiple malignancies. Currently, however, the effect is not universal, with objective response rates (ORR) of about 15–25%, and even lower for some cancers. Abnormal vasculature is a hallmark of most solid tumors and plays a role in immune evasion. Growing body of evidence suggests that vascular normalization and immune reprogramming could operate synergistic effect, resulting in an enhanced therapeutic efficacy. However, the benefit of antitumor efficacy must be weighed against the risk of added toxicity. In this systematic review, we summarize severe toxicity observed in such a kind of combination regimen.</p><p><bold>Methods:</bold> PubMed and Embase were searched for English references published up to May 31, 2019, with MeSH and keywords search terms of immune checkpoint inhibitors (ICIs) and antiangiogenic agents approved for using in solid tumors. Studies performing concomitant use of ICIs and antiangiogenic agents, and also reporting severe treatment-related adverse events (trAEs) (≥grade 3), were included for further analysis.</p><p><bold>Results:</bold> A total of 32 studies including a total of 2,324 participants were analyzed. Limited available data suggests that both antiangiogenic monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs) show potential risk of increasing treatment-related toxicity when combined with ICIs. Overall, the total incidence of severe adverse events (AEs) associated with ICIs plus mAbs (44.5%) is lower than that of ICIs plus TKIs (60.1%). However, the trAEs observed in combination therapy are mostly consistent with the known safety profiles of corresponding monotherapy, and they seem to be largely related to antiangiogenic agents, rather than a true immune-related adverse event (irAE) predominantly due to ICIs. The majority of trAEs are intervened by holding ICI treatment and adding corticosteroids, as well as reducing dose or adjusting administration frequency of the antiangiogenic drugs.</p><p><bold>Conclusions:</bold> Concurrent use of ICIs and antiangiogenic agents shows potential treatment-related toxicity. Further research is required to compare the efficacy and safety of the combination regimen and corresponding monotherapy and identify predictive biomarkers, as well as explore dose, duration, and sequencing schedules of drugs.</p></abstract><kwd-group><kwd>immune checkpoint inhibitor</kwd><kwd>antiangiogenic monoclonal antibody</kwd><kwd>tyrosine kinase inhibitor</kwd><kwd>concurrent therapy</kwd><kwd>treatment-related adverse event</kwd><kwd>immune-related adverse event</kwd><kwd>systematic review</kwd></kwd-group><counts><fig-count count="2"></fig-count><table-count count="4"></table-count><equation-count count="0"></equation-count><ref-count count="92"></ref-count><page-count count="20"></page-count><word-count count="9992"></word-count></counts></article-meta></front></pmc><affiliations><list></list><tree><noCountry><name sortKey="Gao, Ling" sort="Gao, Ling" uniqKey="Gao L" first="Ling" last="Gao">Ling Gao</name><name sortKey="Yang, Xi" sort="Yang, Xi" uniqKey="Yang X" first="Xi" last="Yang">Xi Yang</name><name sortKey="Yi, Cheng" sort="Yi, Cheng" uniqKey="Yi C" first="Cheng" last="Yi">Cheng Yi</name><name sortKey="Zhu, Hong" sort="Zhu, Hong" uniqKey="Zhu H" first="Hong" last="Zhu">Hong Zhu</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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