Clinical activity of pembrolizumab in metastatic prostate cancer with microsatellite instability high (MSI-H) detected by circulating tumor DNA.
Identifieur interne : 000778 ( Main/Exploration ); précédent : 000777; suivant : 000779Clinical activity of pembrolizumab in metastatic prostate cancer with microsatellite instability high (MSI-H) detected by circulating tumor DNA.
Auteurs : Pedro Barata [Oman] ; Neeraj Agarwal [États-Unis] ; Roberto Nussenzveig [États-Unis] ; Benjamin Gerendash [États-Unis] ; Ellen Jaeger [États-Unis] ; Whitley Hatton [États-Unis] ; Elisa Ledet [États-Unis] ; Brian Lewis [États-Unis] ; Jodi Layton [États-Unis] ; Hani Babiker [États-Unis] ; Alan Bryce [États-Unis] ; Rohan Garje [États-Unis] ; Cy Stein [États-Unis] ; Lesli Kiedrowski [États-Unis] ; Philip Saylor [États-Unis] ; Oliver Sartor [États-Unis]Source :
- Journal for immunotherapy of cancer [ 2051-1426 ] ; 2020.
Descripteurs français
- KwdFr :
- ADN tumoral circulant (sang), Adulte d'âge moyen (MeSH), Anticorps monoclonaux humanisés (effets indésirables), Anticorps monoclonaux humanisés (usage thérapeutique), Antinéoplasiques immunologiques (effets indésirables), Antinéoplasiques immunologiques (usage thérapeutique), Biopsie liquide (MeSH), Humains (MeSH), Infections à coronavirus (MeSH), Instabilité des microsatellites (MeSH), Marqueurs biologiques tumoraux (génétique), Mutation (MeSH), Mâle (MeSH), Pandémies (MeSH), Pneumopathie virale (MeSH), Protéine BRCA1 (génétique), Protéine BRCA2 (génétique), Sujet âgé (MeSH), Sujet âgé de 80 ans ou plus (MeSH), Tumeurs de la prostate (anatomopathologie), Tumeurs de la prostate (génétique), Tumeurs de la prostate (traitement médicamenteux).
- MESH :
- anatomopathologie : Tumeurs de la prostate.
- effets indésirables : Anticorps monoclonaux humanisés, Antinéoplasiques immunologiques.
- génétique : Marqueurs biologiques tumoraux, Protéine BRCA1, Protéine BRCA2, Tumeurs de la prostate.
- sang : ADN tumoral circulant.
- traitement médicamenteux : Tumeurs de la prostate.
- usage thérapeutique : Anticorps monoclonaux humanisés, Antinéoplasiques immunologiques.
- Adulte d'âge moyen, Biopsie liquide, Humains, Infections à coronavirus, Instabilité des microsatellites, Mutation, Mâle, Pandémies, Pneumopathie virale, Sujet âgé, Sujet âgé de 80 ans ou plus.
English descriptors
- KwdEn :
- Aged (MeSH), Aged, 80 and over (MeSH), Antibodies, Monoclonal, Humanized (adverse effects), Antibodies, Monoclonal, Humanized (therapeutic use), Antineoplastic Agents, Immunological (adverse effects), Antineoplastic Agents, Immunological (therapeutic use), BRCA1 Protein (genetics), BRCA2 Protein (genetics), Biomarkers, Tumor (genetics), Circulating Tumor DNA (blood), Coronavirus Infections (MeSH), Humans (MeSH), Liquid Biopsy (MeSH), Male (MeSH), Microsatellite Instability (MeSH), Middle Aged (MeSH), Mutation (MeSH), Pandemics (MeSH), Pneumonia, Viral (MeSH), Prostatic Neoplasms (drug therapy), Prostatic Neoplasms (genetics), Prostatic Neoplasms (pathology).
- MESH :
- chemical , adverse effects : Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Immunological.
- chemical , blood : Circulating Tumor DNA.
- chemical , genetics : BRCA1 Protein, BRCA2 Protein, Biomarkers, Tumor.
- chemical , therapeutic use : Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Immunological.
- drug therapy : Prostatic Neoplasms.
- genetics : Prostatic Neoplasms.
- pathology : Prostatic Neoplasms.
- Aged, Aged, 80 and over, Coronavirus Infections, Humans, Liquid Biopsy, Male, Microsatellite Instability, Middle Aged, Mutation, Pandemics, Pneumonia, Viral.
Abstract
To report a multi-institutional case series of patients with advanced microsatellite instability high (MSI-H) prostate adenocarcinoma identified with clinical cell-free DNA (cfDNA) next-generation sequencing (NGS) testing and treated with immune checkpoint inhibitors. Retrospective analysis of patients with metastatic castration-resistant prostate cancer (mCRPC) and MSI-H tumor detected by a commercially available cfDNA NGS assay Guardant360 (G360, Guardant Health) at eight different Academic Institutions in the USA, from September 2018 to April 2020. From a total of 14 MSI-H metastatic prostate cancer patients at participating centers, nine patients with mCRPC with 56% bone, 33% nodal, 11% liver and 11% soft-tissue metastases and a median PSA of 29.3 ng/dL, were treated with pembrolizumab after 2 lines of therapy for CRPC. The estimated median time on pembrolizumab was 9.9 (95% CI 1.0 to 18.8) months. Four patients (44%) achieved PSA50 after a median of 4 (3-12) weeks after treatment initiation including three patients with >99% PSA decline. Among the patients evaluable for radiographic response (n=5), the response rate was 60% with one complete response and two partial responses. Best response was observed after a median of 3.3 (1.4-7.6) months. At time of cut-off, four patients were still on pembrolizumab while four patients discontinued therapy due to progressive disease and one due to COVID-19 infection. Half of the patients with PSA50 had both MSI-H and pathogenic alterations in BRCA1 and BRCA2 in their G360 assays. The use of liquid biopsy to identify metastatic prostate cancer patients with MSI-H is feasible in clinical practice and may overcome some of the obstacles associated with prostate cancer tumor tissue testing. The robust activity of pembrolizumab in selected patients supports the generalized testing for MSI-H.
DOI: 10.1136/jitc-2020-001065
PubMed: 32788235
PubMed Central: PMC7422632
Affiliations:
- Oman, États-Unis
- Arizona, Californie, Iowa, Louisiane, Massachusetts, Utah
- Iowa City
- Université de l'Iowa
Links toward previous steps (curation, corpus...)
Le document en format XML
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sort="Babiker, Hani" uniqKey="Babiker H" first="Hani" last="Babiker">Hani Babiker</name><affiliation wicri:level="2"><nlm:affiliation>Department of Medicine, University of Arizona Arizona Cancer Center, Tucson, Arizona, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, University of Arizona Arizona Cancer Center, Tucson, Arizona</wicri:regionArea><placeName><region type="state">Arizona</region></placeName></affiliation></author><author><name sortKey="Bryce, Alan" sort="Bryce, Alan" uniqKey="Bryce A" first="Alan" last="Bryce">Alan Bryce</name><affiliation wicri:level="2"><nlm:affiliation>Department of Oncology, Mayo Clinic, Scottsdale, Arizona, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Oncology, Mayo Clinic, Scottsdale, Arizona</wicri:regionArea><placeName><region type="state">Arizona</region></placeName></affiliation></author><author><name sortKey="Garje, Rohan" sort="Garje, 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wicri:level="2"><nlm:affiliation>Guardant Health Inc, Redwood City, California, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Guardant Health Inc, Redwood City, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Saylor, Philip" sort="Saylor, Philip" uniqKey="Saylor P" first="Philip" last="Saylor">Philip Saylor</name><affiliation wicri:level="2"><nlm:affiliation>Department of Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Oncology, Massachusetts General Hospital, Boston, Massachusetts</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Sartor, Oliver" sort="Sartor, Oliver" uniqKey="Sartor O" first="Oliver" last="Sartor">Oliver Sartor</name><affiliation wicri:level="2"><nlm:affiliation>Deming Department of Medicine, Tulane University, New Orleans, Louisiana, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Deming Department of Medicine, Tulane University, New Orleans, Louisiana</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32788235</idno><idno type="pmid">32788235</idno><idno type="doi">10.1136/jitc-2020-001065</idno><idno type="pmc">PMC7422632</idno><idno type="wicri:Area/Main/Corpus">000689</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000689</idno><idno type="wicri:Area/Main/Curation">000689</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000689</idno><idno type="wicri:Area/Main/Exploration">000689</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Clinical activity of pembrolizumab in metastatic prostate cancer with microsatellite instability high (MSI-H) detected by circulating tumor DNA.</title><author><name sortKey="Barata, Pedro" sort="Barata, Pedro" uniqKey="Barata P" first="Pedro" last="Barata">Pedro Barata</name><affiliation wicri:level="1"><nlm:affiliation>Deming Department of Medicine, Tulane University, New Orleans, Louisiana, USA pedrobaratamd@gmail.com.</nlm:affiliation><country wicri:rule="url">Oman</country><wicri:regionArea>Deming Department of Medicine, Tulane University, New Orleans, Louisiana</wicri:regionArea><wicri:noRegion>Louisiana</wicri:noRegion></affiliation></author><author><name sortKey="Agarwal, Neeraj" sort="Agarwal, Neeraj" uniqKey="Agarwal N" first="Neeraj" last="Agarwal">Neeraj Agarwal</name><affiliation wicri:level="2"><nlm:affiliation>Department of Medical Oncology, University of Utah, Salt Lake City, Utah, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medical Oncology, University of Utah, Salt Lake City, Utah</wicri:regionArea><placeName><region type="state">Utah</region></placeName></affiliation></author><author><name sortKey="Nussenzveig, Roberto" sort="Nussenzveig, Roberto" uniqKey="Nussenzveig R" first="Roberto" last="Nussenzveig">Roberto Nussenzveig</name><affiliation wicri:level="2"><nlm:affiliation>Department of Medical Oncology, University of Utah, Salt Lake City, Utah, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medical Oncology, University of Utah, Salt Lake City, Utah</wicri:regionArea><placeName><region type="state">Utah</region></placeName></affiliation></author><author><name sortKey="Gerendash, Benjamin" sort="Gerendash, Benjamin" uniqKey="Gerendash B" first="Benjamin" last="Gerendash">Benjamin Gerendash</name><affiliation wicri:level="2"><nlm:affiliation>Department of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, California, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Jaeger, Ellen" sort="Jaeger, Ellen" uniqKey="Jaeger E" first="Ellen" last="Jaeger">Ellen Jaeger</name><affiliation wicri:level="2"><nlm:affiliation>Deming Department of Medicine, Tulane University, New Orleans, Louisiana, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Deming Department of Medicine, Tulane University, New Orleans, Louisiana</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation></author><author><name sortKey="Hatton, Whitley" sort="Hatton, Whitley" uniqKey="Hatton W" first="Whitley" last="Hatton">Whitley Hatton</name><affiliation wicri:level="2"><nlm:affiliation>Deming Department of Medicine, Tulane University, New Orleans, Louisiana, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Deming Department of Medicine, Tulane University, New Orleans, Louisiana</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation></author><author><name sortKey="Ledet, Elisa" sort="Ledet, Elisa" uniqKey="Ledet E" first="Elisa" last="Ledet">Elisa Ledet</name><affiliation wicri:level="2"><nlm:affiliation>Deming Department of Medicine, Tulane University, New Orleans, Louisiana, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Deming Department of Medicine, Tulane University, New Orleans, Louisiana</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation></author><author><name sortKey="Lewis, Brian" sort="Lewis, Brian" uniqKey="Lewis B" first="Brian" last="Lewis">Brian Lewis</name><affiliation wicri:level="2"><nlm:affiliation>Deming Department of Medicine, Tulane University, New Orleans, Louisiana, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Deming Department of Medicine, Tulane University, New Orleans, Louisiana</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation></author><author><name sortKey="Layton, Jodi" sort="Layton, Jodi" uniqKey="Layton J" first="Jodi" last="Layton">Jodi Layton</name><affiliation wicri:level="2"><nlm:affiliation>Deming Department of Medicine, Tulane University, New Orleans, Louisiana, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Deming Department of Medicine, Tulane University, New Orleans, Louisiana</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation></author><author><name sortKey="Babiker, Hani" sort="Babiker, Hani" uniqKey="Babiker H" first="Hani" last="Babiker">Hani Babiker</name><affiliation wicri:level="2"><nlm:affiliation>Department of Medicine, University of Arizona Arizona Cancer Center, Tucson, Arizona, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, University of Arizona Arizona Cancer Center, Tucson, Arizona</wicri:regionArea><placeName><region type="state">Arizona</region></placeName></affiliation></author><author><name sortKey="Bryce, Alan" sort="Bryce, Alan" uniqKey="Bryce A" first="Alan" last="Bryce">Alan Bryce</name><affiliation wicri:level="2"><nlm:affiliation>Department of Oncology, Mayo Clinic, Scottsdale, Arizona, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Oncology, Mayo Clinic, Scottsdale, Arizona</wicri:regionArea><placeName><region type="state">Arizona</region></placeName></affiliation></author><author><name sortKey="Garje, Rohan" sort="Garje, Rohan" uniqKey="Garje R" first="Rohan" last="Garje">Rohan Garje</name><affiliation wicri:level="4"><nlm:affiliation>Division of Hematology, Oncology, and Blood and Marrow Transplant, University of Iowa, Iowa City, Iowa, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Hematology, Oncology, and Blood and Marrow Transplant, University of Iowa, Iowa City, Iowa</wicri:regionArea><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Genitourinary Oncology Program, Division of Hematology, Oncology and Blood and Marrow Transplantation, The University of Iowa, Iowa City, Iowa, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Genitourinary Oncology Program, Division of Hematology, Oncology and Blood and Marrow Transplantation, The University of Iowa, Iowa City, Iowa</wicri:regionArea><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Stein, Cy" sort="Stein, Cy" uniqKey="Stein C" first="Cy" last="Stein">Cy Stein</name><affiliation wicri:level="2"><nlm:affiliation>Department of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, California, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Kiedrowski, Lesli" sort="Kiedrowski, Lesli" uniqKey="Kiedrowski L" first="Lesli" last="Kiedrowski">Lesli Kiedrowski</name><affiliation wicri:level="2"><nlm:affiliation>Guardant Health Inc, Redwood City, California, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Guardant Health Inc, Redwood City, California</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Saylor, Philip" sort="Saylor, Philip" uniqKey="Saylor P" first="Philip" last="Saylor">Philip Saylor</name><affiliation wicri:level="2"><nlm:affiliation>Department of Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Oncology, Massachusetts General Hospital, Boston, Massachusetts</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Sartor, Oliver" sort="Sartor, Oliver" uniqKey="Sartor O" first="Oliver" last="Sartor">Oliver Sartor</name><affiliation wicri:level="2"><nlm:affiliation>Deming Department of Medicine, Tulane University, New Orleans, Louisiana, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Deming Department of Medicine, Tulane University, New Orleans, Louisiana</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation></author></analytic><series><title level="j">Journal for immunotherapy of cancer</title><idno type="eISSN">2051-1426</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged (MeSH)</term><term>Aged, 80 and over (MeSH)</term><term>Antibodies, Monoclonal, Humanized (adverse effects)</term><term>Antibodies, Monoclonal, Humanized (therapeutic use)</term><term>Antineoplastic Agents, Immunological (adverse effects)</term><term>Antineoplastic Agents, Immunological (therapeutic use)</term><term>BRCA1 Protein (genetics)</term><term>BRCA2 Protein (genetics)</term><term>Biomarkers, Tumor (genetics)</term><term>Circulating Tumor DNA (blood)</term><term>Coronavirus Infections (MeSH)</term><term>Humans (MeSH)</term><term>Liquid Biopsy (MeSH)</term><term>Male (MeSH)</term><term>Microsatellite Instability (MeSH)</term><term>Middle Aged (MeSH)</term><term>Mutation (MeSH)</term><term>Pandemics (MeSH)</term><term>Pneumonia, Viral (MeSH)</term><term>Prostatic Neoplasms (drug therapy)</term><term>Prostatic Neoplasms (genetics)</term><term>Prostatic Neoplasms (pathology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ADN tumoral circulant (sang)</term><term>Adulte d'âge moyen (MeSH)</term><term>Anticorps monoclonaux humanisés (effets indésirables)</term><term>Anticorps monoclonaux humanisés (usage thérapeutique)</term><term>Antinéoplasiques immunologiques (effets indésirables)</term><term>Antinéoplasiques immunologiques (usage thérapeutique)</term><term>Biopsie liquide (MeSH)</term><term>Humains (MeSH)</term><term>Infections à coronavirus (MeSH)</term><term>Instabilité des microsatellites (MeSH)</term><term>Marqueurs biologiques tumoraux (génétique)</term><term>Mutation (MeSH)</term><term>Mâle (MeSH)</term><term>Pandémies (MeSH)</term><term>Pneumopathie virale (MeSH)</term><term>Protéine BRCA1 (génétique)</term><term>Protéine BRCA2 (génétique)</term><term>Sujet âgé (MeSH)</term><term>Sujet âgé de 80 ans ou plus (MeSH)</term><term>Tumeurs de la prostate (anatomopathologie)</term><term>Tumeurs de la prostate (génétique)</term><term>Tumeurs de la prostate (traitement médicamenteux)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Antibodies, Monoclonal, Humanized</term><term>Antineoplastic Agents, Immunological</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Circulating Tumor DNA</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>BRCA1 Protein</term><term>BRCA2 Protein</term><term>Biomarkers, Tumor</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antibodies, Monoclonal, Humanized</term><term>Antineoplastic Agents, Immunological</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Tumeurs de la prostate</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Prostatic Neoplasms</term></keywords><keywords scheme="MESH" qualifier="effets indésirables" xml:lang="fr"><term>Anticorps monoclonaux humanisés</term><term>Antinéoplasiques immunologiques</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Prostatic Neoplasms</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Marqueurs biologiques tumoraux</term><term>Protéine BRCA1</term><term>Protéine BRCA2</term><term>Tumeurs de la prostate</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Prostatic Neoplasms</term></keywords><keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>ADN tumoral circulant</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Tumeurs de la prostate</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Anticorps monoclonaux humanisés</term><term>Antinéoplasiques immunologiques</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Aged, 80 and over</term><term>Coronavirus Infections</term><term>Humans</term><term>Liquid Biopsy</term><term>Male</term><term>Microsatellite Instability</term><term>Middle Aged</term><term>Mutation</term><term>Pandemics</term><term>Pneumonia, Viral</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte d'âge moyen</term><term>Biopsie liquide</term><term>Humains</term><term>Infections à coronavirus</term><term>Instabilité des microsatellites</term><term>Mutation</term><term>Mâle</term><term>Pandémies</term><term>Pneumopathie virale</term><term>Sujet âgé</term><term>Sujet âgé de 80 ans ou plus</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">To report a multi-institutional case series of patients with advanced microsatellite instability high (MSI-H) prostate adenocarcinoma identified with clinical cell-free DNA (cfDNA) next-generation sequencing (NGS) testing and treated with immune checkpoint inhibitors. Retrospective analysis of patients with metastatic castration-resistant prostate cancer (mCRPC) and MSI-H tumor detected by a commercially available cfDNA NGS assay Guardant360 (G360, Guardant Health) at eight different Academic Institutions in the USA, from September 2018 to April 2020. From a total of 14 MSI-H metastatic prostate cancer patients at participating centers, nine patients with mCRPC with 56% bone, 33% nodal, 11% liver and 11% soft-tissue metastases and a median PSA of 29.3 ng/dL, were treated with pembrolizumab after 2 lines of therapy for CRPC. The estimated median time on pembrolizumab was 9.9 (95% CI 1.0 to 18.8) months. Four patients (44%) achieved PSA50 after a median of 4 (3-12) weeks after treatment initiation including three patients with >99% PSA decline. Among the patients evaluable for radiographic response (n=5), the response rate was 60% with one complete response and two partial responses. Best response was observed after a median of 3.3 (1.4-7.6) months. At time of cut-off, four patients were still on pembrolizumab while four patients discontinued therapy due to progressive disease and one due to COVID-19 infection. Half of the patients with PSA50 had both MSI-H and pathogenic alterations in <i>BRCA1</i> and <i>BRCA2</i> in their G360 assays. The use of liquid biopsy to identify metastatic prostate cancer patients with MSI-H is feasible in clinical practice and may overcome some of the obstacles associated with prostate cancer tumor tissue testing. The robust activity of pembrolizumab in selected patients supports the generalized testing for MSI-H.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32788235</PMID><DateCompleted><Year>2020</Year><Month>09</Month><Day>02</Day></DateCompleted><DateRevised><Year>2020</Year><Month>09</Month><Day>02</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">2051-1426</ISSN><JournalIssue CitedMedium="Internet"><Volume>8</Volume><Issue>2</Issue><PubDate><Year>2020</Year><Month>08</Month></PubDate></JournalIssue><Title>Journal for immunotherapy of cancer</Title><ISOAbbreviation>J Immunother Cancer</ISOAbbreviation></Journal><ArticleTitle>Clinical activity of pembrolizumab in metastatic prostate cancer with microsatellite instability high (MSI-H) detected by circulating tumor DNA.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">e001065</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1136/jitc-2020-001065</ELocationID><Abstract><AbstractText>To report a multi-institutional case series of patients with advanced microsatellite instability high (MSI-H) prostate adenocarcinoma identified with clinical cell-free DNA (cfDNA) next-generation sequencing (NGS) testing and treated with immune checkpoint inhibitors. Retrospective analysis of patients with metastatic castration-resistant prostate cancer (mCRPC) and MSI-H tumor detected by a commercially available cfDNA NGS assay Guardant360 (G360, Guardant Health) at eight different Academic Institutions in the USA, from September 2018 to April 2020. From a total of 14 MSI-H metastatic prostate cancer patients at participating centers, nine patients with mCRPC with 56% bone, 33% nodal, 11% liver and 11% soft-tissue metastases and a median PSA of 29.3 ng/dL, were treated with pembrolizumab after 2 lines of therapy for CRPC. The estimated median time on pembrolizumab was 9.9 (95% CI 1.0 to 18.8) months. Four patients (44%) achieved PSA50 after a median of 4 (3-12) weeks after treatment initiation including three patients with >99% PSA decline. Among the patients evaluable for radiographic response (n=5), the response rate was 60% with one complete response and two partial responses. Best response was observed after a median of 3.3 (1.4-7.6) months. At time of cut-off, four patients were still on pembrolizumab while four patients discontinued therapy due to progressive disease and one due to COVID-19 infection. Half of the patients with PSA50 had both MSI-H and pathogenic alterations in <i>BRCA1</i> and <i>BRCA2</i> in their G360 assays. The use of liquid biopsy to identify metastatic prostate cancer patients with MSI-H is feasible in clinical practice and may overcome some of the obstacles associated with prostate cancer tumor tissue testing. The robust activity of pembrolizumab in selected patients supports the generalized testing for MSI-H.</AbstractText><CopyrightInformation>© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Barata</LastName><ForeName>Pedro</ForeName><Initials>P</Initials><Identifier Source="ORCID">0000-0002-8890-2951</Identifier><AffiliationInfo><Affiliation>Deming Department of Medicine, Tulane University, New Orleans, Louisiana, USA pedrobaratamd@gmail.com.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Agarwal</LastName><ForeName>Neeraj</ForeName><Initials>N</Initials><Identifier Source="ORCID">0000-0003-1076-0428</Identifier><AffiliationInfo><Affiliation>Department of Medical Oncology, University of Utah, Salt Lake City, Utah, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nussenzveig</LastName><ForeName>Roberto</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Medical Oncology, University of Utah, Salt Lake City, Utah, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gerendash</LastName><ForeName>Benjamin</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Department of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, California, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jaeger</LastName><ForeName>Ellen</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Deming Department of Medicine, Tulane University, New Orleans, Louisiana, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hatton</LastName><ForeName>Whitley</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Deming Department of Medicine, Tulane University, New Orleans, Louisiana, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ledet</LastName><ForeName>Elisa</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Deming Department of Medicine, Tulane University, New Orleans, Louisiana, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lewis</LastName><ForeName>Brian</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Deming Department of Medicine, Tulane University, New Orleans, Louisiana, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Layton</LastName><ForeName>Jodi</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Deming Department of Medicine, Tulane University, New Orleans, Louisiana, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Babiker</LastName><ForeName>Hani</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Medicine, University of Arizona Arizona Cancer Center, Tucson, Arizona, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bryce</LastName><ForeName>Alan</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Oncology, Mayo Clinic, Scottsdale, Arizona, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Garje</LastName><ForeName>Rohan</ForeName><Initials>R</Initials><Identifier Source="ORCID">0000-0002-7244-5602</Identifier><AffiliationInfo><Affiliation>Division of Hematology, Oncology, and Blood and Marrow Transplant, University of Iowa, Iowa City, Iowa, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Genitourinary Oncology Program, Division of Hematology, Oncology and Blood and Marrow Transplantation, The University of Iowa, Iowa City, Iowa, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Stein</LastName><ForeName>Cy</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, California, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kiedrowski</LastName><ForeName>Lesli</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Guardant Health Inc, Redwood City, California, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Saylor</LastName><ForeName>Philip</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sartor</LastName><ForeName>Oliver</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>Deming Department of Medicine, Tulane University, New Orleans, Louisiana, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016448">Multicenter Study</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>J Immunother Cancer</MedlineTA><NlmUniqueID>101620585</NlmUniqueID><ISSNLinking>2051-1426</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D061067">Antibodies, Monoclonal, Humanized</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000074322">Antineoplastic Agents, Immunological</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D019313">BRCA1 Protein</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C492913">BRCA1 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D024682">BRCA2 Protein</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C551750">BRCA2 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014408">Biomarkers, Tumor</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000074141">Circulating Tumor DNA</NameOfSubstance></Chemical><Chemical><RegistryNumber>DPT0O3T46P</RegistryNumber><NameOfSubstance UI="C582435">pembrolizumab</NameOfSubstance></Chemical></ChemicalList><SupplMeshList><SupplMeshName Type="Disease" UI="C000657245">COVID-19</SupplMeshName></SupplMeshList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000369" MajorTopicYN="N">Aged, 80 and over</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D061067" MajorTopicYN="N">Antibodies, Monoclonal, Humanized</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000074322" MajorTopicYN="N">Antineoplastic Agents, Immunological</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019313" MajorTopicYN="N">BRCA1 Protein</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D024682" MajorTopicYN="N">BRCA2 Protein</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014408" MajorTopicYN="N">Biomarkers, Tumor</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000074141" MajorTopicYN="N">Circulating Tumor DNA</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018352" MajorTopicYN="N">Coronavirus Infections</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000073890" MajorTopicYN="N">Liquid Biopsy</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D053842" MajorTopicYN="Y">Microsatellite Instability</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009154" MajorTopicYN="N">Mutation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D058873" MajorTopicYN="N">Pandemics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011024" MajorTopicYN="N">Pneumonia, Viral</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011471" MajorTopicYN="N">Prostatic Neoplasms</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">biomarkers</Keyword><Keyword MajorTopicYN="Y">immunotherapy</Keyword><Keyword MajorTopicYN="Y">programmed cell death 1 receptor</Keyword><Keyword MajorTopicYN="Y">prostatic neoplasms</Keyword><Keyword MajorTopicYN="Y">tumor</Keyword></KeywordList><CoiStatement>Competing interests: PB has a consulting/advisory role (Institution) with Exelixis, Caris, Bayer, Janssen, EMD/Serono, Pfizer, Astellas, Dendreon, Clovis and Sanofi. Contracted Research (Institution) from Seattle Genetics, BlueEarth Diagnostics, Nektar, AstraZeneca and Seattle Genetics. NA has a consulting/advisory role with Astellas, Astra Zeneca, Bayer, Bristol Myers Squibb, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Foundation Medicine, Genentech, Janssen, Merck, Nektar, Novartis, Pfizer, Pharmacyclics and Seattle Genetics. Contracted Research (Instituion) from Astra Zeneca, Bavarian Nordic, Bayer, BN immunotherapeutics, Bristol Myers Squibb, Calithera, Celldex, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Glaxo Smith Kline, Immunomedics, Janssen, Medivation, Merck, Nektar, New Link Genetics, Novartis, Pfizer, Prometheus, Rexahn, Roche, Sanofi, Seattle Genetics, Takeda and Tracon. HB has a consulting/advisory role with Endocyte, Celgene, Guardant360, Tracon. Honoraria: SirTex, Bayer. Speaker Bureau: Guardant360. LK is employee of Guardant Health. OS has a consulting/advisory role with AAA, Astellas, Astrazeneca, Bayer, Blue Earth Diagnostics, EMD Serono, Endocyte, Pfizer, Progenics, Sanofi, Invitae, Merck, Novartis, Janseen, Constellation, Dendreon, BMS, Bravarin Nordic, Clovis, Myriad, Noria Therapeutics, Noxopharm, Point Biopharma and Tenebio. Contracted Research from Innocrin, Sotio. He also serves as consultant on NCI Scientific Board Counselors and is a cochairman of GU Committee at NRG.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>07</Month><Day>19</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>8</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>8</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>9</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32788235</ArticleId><ArticleId IdType="pii">jitc-2020-001065</ArticleId><ArticleId IdType="doi">10.1136/jitc-2020-001065</ArticleId><ArticleId IdType="pmc">PMC7422632</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>J Mol Diagn. 2006 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last="Barata">Pedro Barata</name></noRegion></country><country name="États-Unis"><region name="Utah"><name sortKey="Agarwal, Neeraj" sort="Agarwal, Neeraj" uniqKey="Agarwal N" first="Neeraj" last="Agarwal">Neeraj Agarwal</name></region><name sortKey="Babiker, Hani" sort="Babiker, Hani" uniqKey="Babiker H" first="Hani" last="Babiker">Hani Babiker</name><name sortKey="Bryce, Alan" sort="Bryce, Alan" uniqKey="Bryce A" first="Alan" last="Bryce">Alan Bryce</name><name sortKey="Garje, Rohan" sort="Garje, Rohan" uniqKey="Garje R" first="Rohan" last="Garje">Rohan Garje</name><name sortKey="Garje, Rohan" sort="Garje, Rohan" uniqKey="Garje R" first="Rohan" last="Garje">Rohan Garje</name><name sortKey="Gerendash, Benjamin" sort="Gerendash, Benjamin" uniqKey="Gerendash B" first="Benjamin" last="Gerendash">Benjamin Gerendash</name><name sortKey="Hatton, Whitley" sort="Hatton, Whitley" uniqKey="Hatton W" first="Whitley" last="Hatton">Whitley Hatton</name><name sortKey="Jaeger, Ellen" sort="Jaeger, Ellen" uniqKey="Jaeger E" first="Ellen" last="Jaeger">Ellen Jaeger</name><name sortKey="Kiedrowski, Lesli" sort="Kiedrowski, Lesli" uniqKey="Kiedrowski L" first="Lesli" last="Kiedrowski">Lesli Kiedrowski</name><name sortKey="Layton, Jodi" sort="Layton, Jodi" uniqKey="Layton J" first="Jodi" last="Layton">Jodi Layton</name><name sortKey="Ledet, Elisa" sort="Ledet, Elisa" uniqKey="Ledet E" first="Elisa" last="Ledet">Elisa Ledet</name><name sortKey="Lewis, Brian" sort="Lewis, Brian" uniqKey="Lewis B" first="Brian" last="Lewis">Brian Lewis</name><name sortKey="Nussenzveig, Roberto" sort="Nussenzveig, Roberto" uniqKey="Nussenzveig R" first="Roberto" last="Nussenzveig">Roberto Nussenzveig</name><name sortKey="Sartor, Oliver" sort="Sartor, Oliver" uniqKey="Sartor O" first="Oliver" last="Sartor">Oliver Sartor</name><name sortKey="Saylor, Philip" sort="Saylor, Philip" uniqKey="Saylor P" first="Philip" last="Saylor">Philip Saylor</name><name sortKey="Stein, Cy" sort="Stein, Cy" uniqKey="Stein C" 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|texte= Clinical activity of pembrolizumab in metastatic prostate cancer with microsatellite instability high (MSI-H) detected by circulating tumor DNA.
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Pour générer des pages wiki
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| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a CovidSeniorV1
| This area was generated with Dilib version V0.6.37. |  |