A Phase I Study of the CDK4/6 Inhibitor Ribociclib (LEE011) in Pediatric Patients with Malignant Rhabdoid Tumors, Neuroblastoma, and Other Solid Tumors.
Identifieur interne : 000C19 ( PubMed/Curation ); précédent : 000C18; suivant : 000C20A Phase I Study of the CDK4/6 Inhibitor Ribociclib (LEE011) in Pediatric Patients with Malignant Rhabdoid Tumors, Neuroblastoma, and Other Solid Tumors.
Auteurs : Birgit Geoerger [France] ; Franck Bourdeaut [France] ; Steven G. Dubois [États-Unis] ; Matthias Fischer [Allemagne] ; James I. Geller [États-Unis] ; Nicholas G. Gottardo [Australie] ; Aurélien Marabelle [France] ; Andrew D J. Pearson ; Shakeel Modak [États-Unis] ; Thomas Cash [Géorgie (pays)] ; Giles W. Robinson [États-Unis] ; Marlyane Motta [États-Unis] ; Alessandro Matano [Suisse] ; Suraj G. Bhansali [États-Unis] ; Jason R. Dobson [États-Unis] ; Sudha Parasuraman [États-Unis] ; Susan N. Chi [États-Unis]Source :
- Clinical cancer research : an official journal of the American Association for Cancer Research [ 1078-0432 ] ; 2017.
Abstract
Purpose: The cyclin-dependent kinase (CDK) 4/6 inhibitor, ribociclib (LEE011), displayed preclinical activity in neuroblastoma and malignant rhabdoid tumor (MRT) models. In this phase I study, the maximum tolerated dose (MTD) and recommended phase II dose (RP2D), safety, pharmacokinetics (PK), and preliminary activity of single-agent ribociclib were investigated in pediatric patients with neuroblastoma, MRT, or other cyclin D-CDK4/6-INK4-retinoblastoma pathway-altered tumors.Experimental Design: Patients (aged 1-21 years) received escalating once-daily oral doses of ribociclib (3-weeks-on/1-week-off). Dose escalation was guided by a Bayesian logistic regression model with overdose control and real-time PK.Results: Thirty-two patients (median age, 5.5 years) received ribociclib 280, 350, or 470 mg/m(2) Three patients had dose-limiting toxicities of grade 3 fatigue (280 mg/m(2); n = 1) or grade 4 thrombocytopenia (470 mg/m(2); n = 2). Most common treatment-related adverse events (AE) were hematologic: neutropenia (72% all-grade/63% grade 3/4), leukopenia (63%/38%), anemia (44%/3%), thrombocytopenia (44%/28%), and lymphopenia (38%/19%), followed by vomiting (38%/0%), fatigue (25%/3%), nausea (25%/0%), and QTc prolongation (22%/0%). Ribociclib exposure was dose-dependent at 350 and 470 mg/m(2) [equivalent to 600 (RP2D)-900 mg in adults], with high interpatient variability. Best overall response was stable disease (SD) in nine patients (seven with neuroblastoma, two with primary CNS MRT); five patients achieved SD for more than 6, 6, 8, 12, and 13 cycles, respectively.Conclusions: Ribociclib demonstrated acceptable safety and PK in pediatric patients. MTD (470 mg/m(2)) and RP2D (350 mg/m(2)) were equivalent to those in adults. Observations of prolonged SD support further investigation of ribociclib combined with other agents in neuroblastoma and MRT. Clin Cancer Res; 23(10); 2433-41. ©2017 AACR.
DOI: 10.1158/1078-0432.CCR-16-2898
PubMed: 28432176
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Andrew D J. Pearson<affiliation><nlm:affiliation>The Royal Marsden NHS Foundation Trust & Institute of Cancer Research, The Royal Marsden Hospital, Sutton, United Kingdom (Retired).</nlm:affiliation>
<wicri:noCountry code="subField">United Kingdom (Retired)</wicri:noCountry>
</affiliation>
Le document en format XML
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<author><name sortKey="Cash, Thomas" sort="Cash, Thomas" uniqKey="Cash T" first="Thomas" last="Cash">Thomas Cash</name>
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<author><name sortKey="Robinson, Giles W" sort="Robinson, Giles W" uniqKey="Robinson G" first="Giles W" last="Robinson">Giles W. Robinson</name>
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<author><name sortKey="Motta, Marlyane" sort="Motta, Marlyane" uniqKey="Motta M" first="Marlyane" last="Motta">Marlyane Motta</name>
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<author><name sortKey="Matano, Alessandro" sort="Matano, Alessandro" uniqKey="Matano A" first="Alessandro" last="Matano">Alessandro Matano</name>
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<author><name sortKey="Chi, Susan N" sort="Chi, Susan N" uniqKey="Chi S" first="Susan N" last="Chi">Susan N. Chi</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">A Phase I Study of the CDK4/6 Inhibitor Ribociclib (LEE011) in Pediatric Patients with Malignant Rhabdoid Tumors, Neuroblastoma, and Other Solid Tumors.</title>
<author><name sortKey="Geoerger, Birgit" sort="Geoerger, Birgit" uniqKey="Geoerger B" first="Birgit" last="Geoerger">Birgit Geoerger</name>
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<author><name sortKey="Dubois, Steven G" sort="Dubois, Steven G" uniqKey="Dubois S" first="Steven G" last="Dubois">Steven G. Dubois</name>
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<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Pediatric Oncology and Hematology, University Children's Hospital of Cologne, Medical Faculty and Center for Molecular Medicine Cologne (CMMC), University of Cologne; Max Planck Institute for Metabolism Research, Cologne</wicri:regionArea>
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<author><name sortKey="Geller, James I" sort="Geller, James I" uniqKey="Geller J" first="James I" last="Geller">James I. Geller</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Ohio</region>
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<wicri:cityArea>UC Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati</wicri:cityArea>
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<author><name sortKey="Gottardo, Nicholas G" sort="Gottardo, Nicholas G" uniqKey="Gottardo N" first="Nicholas G" last="Gottardo">Nicholas G. Gottardo</name>
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<country xml:lang="fr">Australie</country>
<wicri:regionArea>Princess Margaret Hospital for Children, Perth, Western Australia</wicri:regionArea>
</affiliation>
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<author><name sortKey="Marabelle, Aurelien" sort="Marabelle, Aurelien" uniqKey="Marabelle A" first="Aurélien" last="Marabelle">Aurélien Marabelle</name>
<affiliation wicri:level="1"><nlm:affiliation>Institute for Pediatric HematoOncology, Léon Bérard Cancer Center, Lyon, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institute for Pediatric HematoOncology, Léon Bérard Cancer Center, Lyon</wicri:regionArea>
</affiliation>
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<author><name sortKey="Pearson, Andrew D J" sort="Pearson, Andrew D J" uniqKey="Pearson A" first="Andrew D J" last="Pearson">Andrew D J. Pearson</name>
<affiliation><nlm:affiliation>The Royal Marsden NHS Foundation Trust & Institute of Cancer Research, The Royal Marsden Hospital, Sutton, United Kingdom (Retired).</nlm:affiliation>
<wicri:noCountry code="subField">United Kingdom (Retired)</wicri:noCountry>
</affiliation>
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<author><name sortKey="Modak, Shakeel" sort="Modak, Shakeel" uniqKey="Modak S" first="Shakeel" last="Modak">Shakeel Modak</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York</wicri:cityArea>
</affiliation>
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<author><name sortKey="Cash, Thomas" sort="Cash, Thomas" uniqKey="Cash T" first="Thomas" last="Cash">Thomas Cash</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Pediatrics, Children's Healthcare of Atlanta, Emory University, Atlanta, Georgia.</nlm:affiliation>
<country xml:lang="fr">Géorgie (pays)</country>
<wicri:regionArea>Department of Pediatrics, Children's Healthcare of Atlanta, Emory University, Atlanta</wicri:regionArea>
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<author><name sortKey="Robinson, Giles W" sort="Robinson, Giles W" uniqKey="Robinson G" first="Giles W" last="Robinson">Giles W. Robinson</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Tennessee</region>
</placeName>
<wicri:cityArea>Department of Oncology, St. Jude Children's Research Hospital, Memphis</wicri:cityArea>
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<author><name sortKey="Motta, Marlyane" sort="Motta, Marlyane" uniqKey="Motta M" first="Marlyane" last="Motta">Marlyane Motta</name>
<affiliation wicri:level="2"><nlm:affiliation>Translational Clinical Oncology, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Translational Clinical Oncology, Novartis Institutes for BioMedical Research, Cambridge</wicri:cityArea>
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<author><name sortKey="Matano, Alessandro" sort="Matano, Alessandro" uniqKey="Matano A" first="Alessandro" last="Matano">Alessandro Matano</name>
<affiliation wicri:level="1"><nlm:affiliation>Translational Clinical Oncology, Novartis Pharma AG, Basel, Switzerland.</nlm:affiliation>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Translational Clinical Oncology, Novartis Pharma AG, Basel</wicri:regionArea>
</affiliation>
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<author><name sortKey="Bhansali, Suraj G" sort="Bhansali, Suraj G" uniqKey="Bhansali S" first="Suraj G" last="Bhansali">Suraj G. Bhansali</name>
<affiliation wicri:level="2"><nlm:affiliation>Clinical Pharmacology, Translational Clinical Oncology, Novartis Institutes for BioMedical Research, East Hanover, New Jersey.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">New Jersey</region>
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<wicri:cityArea>Clinical Pharmacology, Translational Clinical Oncology, Novartis Institutes for BioMedical Research, East Hanover</wicri:cityArea>
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<author><name sortKey="Dobson, Jason R" sort="Dobson, Jason R" uniqKey="Dobson J" first="Jason R" last="Dobson">Jason R. Dobson</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
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<author><name sortKey="Parasuraman, Sudha" sort="Parasuraman, Sudha" uniqKey="Parasuraman S" first="Sudha" last="Parasuraman">Sudha Parasuraman</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Translational Clinical Oncology, Novartis Institutes for BioMedical Research, Cambridge</wicri:cityArea>
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<author><name sortKey="Chi, Susan N" sort="Chi, Susan N" uniqKey="Chi S" first="Susan N" last="Chi">Susan N. Chi</name>
<affiliation wicri:level="2"><nlm:affiliation>Pediatric NeuroOncology, DanaFarber Cancer Institute, Boston, Massachusetts.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
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<wicri:cityArea>Pediatric NeuroOncology, DanaFarber Cancer Institute, Boston</wicri:cityArea>
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<front><div type="abstract" xml:lang="en">Purpose: The cyclin-dependent kinase (CDK) 4/6 inhibitor, ribociclib (LEE011), displayed preclinical activity in neuroblastoma and malignant rhabdoid tumor (MRT) models. In this phase I study, the maximum tolerated dose (MTD) and recommended phase II dose (RP2D), safety, pharmacokinetics (PK), and preliminary activity of single-agent ribociclib were investigated in pediatric patients with neuroblastoma, MRT, or other cyclin D-CDK4/6-INK4-retinoblastoma pathway-altered tumors.Experimental Design: Patients (aged 1-21 years) received escalating once-daily oral doses of ribociclib (3-weeks-on/1-week-off). Dose escalation was guided by a Bayesian logistic regression model with overdose control and real-time PK.Results: Thirty-two patients (median age, 5.5 years) received ribociclib 280, 350, or 470 mg/m(2) Three patients had dose-limiting toxicities of grade 3 fatigue (280 mg/m(2); n = 1) or grade 4 thrombocytopenia (470 mg/m(2); n = 2). Most common treatment-related adverse events (AE) were hematologic: neutropenia (72% all-grade/63% grade 3/4), leukopenia (63%/38%), anemia (44%/3%), thrombocytopenia (44%/28%), and lymphopenia (38%/19%), followed by vomiting (38%/0%), fatigue (25%/3%), nausea (25%/0%), and QTc prolongation (22%/0%). Ribociclib exposure was dose-dependent at 350 and 470 mg/m(2) [equivalent to 600 (RP2D)-900 mg in adults], with high interpatient variability. Best overall response was stable disease (SD) in nine patients (seven with neuroblastoma, two with primary CNS MRT); five patients achieved SD for more than 6, 6, 8, 12, and 13 cycles, respectively.Conclusions: Ribociclib demonstrated acceptable safety and PK in pediatric patients. MTD (470 mg/m(2)) and RP2D (350 mg/m(2)) were equivalent to those in adults. Observations of prolonged SD support further investigation of ribociclib combined with other agents in neuroblastoma and MRT. Clin Cancer Res; 23(10); 2433-41. ©2017 AACR.</div>
</front>
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<Month>05</Month>
<Day>16</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Print">1078-0432</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>23</Volume>
<Issue>10</Issue>
<PubDate><Year>2017</Year>
<Month>May</Month>
<Day>15</Day>
</PubDate>
</JournalIssue>
<Title>Clinical cancer research : an official journal of the American Association for Cancer Research</Title>
<ISOAbbreviation>Clin. Cancer Res.</ISOAbbreviation>
</Journal>
<ArticleTitle>A Phase I Study of the CDK4/6 Inhibitor Ribociclib (LEE011) in Pediatric Patients with Malignant Rhabdoid Tumors, Neuroblastoma, and Other Solid Tumors.</ArticleTitle>
<Pagination><MedlinePgn>2433-2441</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1158/1078-0432.CCR-16-2898</ELocationID>
<Abstract><AbstractText>Purpose: The cyclin-dependent kinase (CDK) 4/6 inhibitor, ribociclib (LEE011), displayed preclinical activity in neuroblastoma and malignant rhabdoid tumor (MRT) models. In this phase I study, the maximum tolerated dose (MTD) and recommended phase II dose (RP2D), safety, pharmacokinetics (PK), and preliminary activity of single-agent ribociclib were investigated in pediatric patients with neuroblastoma, MRT, or other cyclin D-CDK4/6-INK4-retinoblastoma pathway-altered tumors.Experimental Design: Patients (aged 1-21 years) received escalating once-daily oral doses of ribociclib (3-weeks-on/1-week-off). Dose escalation was guided by a Bayesian logistic regression model with overdose control and real-time PK.Results: Thirty-two patients (median age, 5.5 years) received ribociclib 280, 350, or 470 mg/m(2) Three patients had dose-limiting toxicities of grade 3 fatigue (280 mg/m(2); n = 1) or grade 4 thrombocytopenia (470 mg/m(2); n = 2). Most common treatment-related adverse events (AE) were hematologic: neutropenia (72% all-grade/63% grade 3/4), leukopenia (63%/38%), anemia (44%/3%), thrombocytopenia (44%/28%), and lymphopenia (38%/19%), followed by vomiting (38%/0%), fatigue (25%/3%), nausea (25%/0%), and QTc prolongation (22%/0%). Ribociclib exposure was dose-dependent at 350 and 470 mg/m(2) [equivalent to 600 (RP2D)-900 mg in adults], with high interpatient variability. Best overall response was stable disease (SD) in nine patients (seven with neuroblastoma, two with primary CNS MRT); five patients achieved SD for more than 6, 6, 8, 12, and 13 cycles, respectively.Conclusions: Ribociclib demonstrated acceptable safety and PK in pediatric patients. MTD (470 mg/m(2)) and RP2D (350 mg/m(2)) were equivalent to those in adults. Observations of prolonged SD support further investigation of ribociclib combined with other agents in neuroblastoma and MRT. Clin Cancer Res; 23(10); 2433-41. ©2017 AACR.</AbstractText>
<CopyrightInformation>©2017 American Association for Cancer Research.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Geoerger</LastName>
<ForeName>Birgit</ForeName>
<Initials>B</Initials>
<AffiliationInfo><Affiliation>Department of Pediatric and Adolescent Oncology, Gustave Roussy and UMR 8203, CNRS, Univ. Paris-Sud, Villejuif, France. birgit.geoerger@gustaveroussy.fr.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bourdeaut</LastName>
<ForeName>Franck</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>Institut Curie, PSL Research University, Department of Pediatric Oncology and INSERM U830, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>DuBois</LastName>
<ForeName>Steven G</ForeName>
<Initials>SG</Initials>
<AffiliationInfo><Affiliation>Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, Massachusetts.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Fischer</LastName>
<ForeName>Matthias</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Department of Pediatric Oncology and Hematology, University Children's Hospital of Cologne, Medical Faculty and Center for Molecular Medicine Cologne (CMMC), University of Cologne; Max Planck Institute for Metabolism Research, Cologne, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Geller</LastName>
<ForeName>James I</ForeName>
<Initials>JI</Initials>
<AffiliationInfo><Affiliation>UC Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gottardo</LastName>
<ForeName>Nicholas G</ForeName>
<Initials>NG</Initials>
<AffiliationInfo><Affiliation>Princess Margaret Hospital for Children, Perth, Western Australia, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Marabelle</LastName>
<ForeName>Aurélien</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Institute for Pediatric HematoOncology, Léon Bérard Cancer Center, Lyon, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Pearson</LastName>
<ForeName>Andrew D J</ForeName>
<Initials>ADJ</Initials>
<AffiliationInfo><Affiliation>The Royal Marsden NHS Foundation Trust & Institute of Cancer Research, The Royal Marsden Hospital, Sutton, United Kingdom (Retired).</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Modak</LastName>
<ForeName>Shakeel</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Cash</LastName>
<ForeName>Thomas</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>Department of Pediatrics, Children's Healthcare of Atlanta, Emory University, Atlanta, Georgia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Robinson</LastName>
<ForeName>Giles W</ForeName>
<Initials>GW</Initials>
<AffiliationInfo><Affiliation>Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Motta</LastName>
<ForeName>Marlyane</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Translational Clinical Oncology, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Matano</LastName>
<ForeName>Alessandro</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Translational Clinical Oncology, Novartis Pharma AG, Basel, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bhansali</LastName>
<ForeName>Suraj G</ForeName>
<Initials>SG</Initials>
<AffiliationInfo><Affiliation>Clinical Pharmacology, Translational Clinical Oncology, Novartis Institutes for BioMedical Research, East Hanover, New Jersey.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Dobson</LastName>
<ForeName>Jason R</ForeName>
<Initials>JR</Initials>
<AffiliationInfo><Affiliation>Translational Clinical Oncology, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Parasuraman</LastName>
<ForeName>Sudha</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Translational Clinical Oncology, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Chi</LastName>
<ForeName>Susan N</ForeName>
<Initials>SN</Initials>
<AffiliationInfo><Affiliation>Pediatric NeuroOncology, DanaFarber Cancer Institute, Boston, Massachusetts.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2017</Year>
<Month>04</Month>
<Day>21</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>Clin Cancer Res</MedlineTA>
<NlmUniqueID>9502500</NlmUniqueID>
<ISSNLinking>1078-0432</ISSNLinking>
</MedlineJournalInfo>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year>
<Month>11</Month>
<Day>17</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="revised"><Year>2016</Year>
<Month>12</Month>
<Day>22</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2017</Year>
<Month>02</Month>
<Day>01</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2017</Year>
<Month>4</Month>
<Day>23</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2017</Year>
<Month>4</Month>
<Day>23</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2017</Year>
<Month>4</Month>
<Day>23</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">28432176</ArticleId>
<ArticleId IdType="pii">1078-0432.CCR-16-2898</ArticleId>
<ArticleId IdType="doi">10.1158/1078-0432.CCR-16-2898</ArticleId>
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