{"id":"https://openalex.org/W2736207382","doi":"https://doi.org/10.1200/jco.2016.34.15_suppl.514","title":"Determination of the maximum tolerated dose (MTD) of the CNS penetrant tyrosine kinase inhibitor (TKI) tesevatinib administered in combination with trastuzumab in HER2+ patients with metastatic breast cancer (BC).","display_name":"Determination of the maximum tolerated dose (MTD) of the CNS penetrant tyrosine kinase inhibitor (TKI) tesevatinib administered in combination with trastuzumab in HER2+ patients with metastatic breast cancer (BC).","publication_year":2016,"publication_date":"2016-05-20","ids":{"openalex":"https://openalex.org/W2736207382","doi":"https://doi.org/10.1200/jco.2016.34.15_suppl.514","mag":"2736207382"},"language":"en","primary_location":{"id":"doi:10.1200/jco.2016.34.15_suppl.514","doi":"https://doi.org/10.1200/jco.2016.34.15_suppl.514","is_oa":false,"landing_page_url":"https://doi.org/10.1200/jco.2016.34.15_suppl.514","pdf_url":null,"source":{"id":"https://openalex.org/S15137598","display_name":"Journal of Clinical Oncology","issn_l":"0732-183X","issn":["0732-183X","1527-7755"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310315671","host_organization_name":"Lippincott Williams & Wilkins","host_organization_lineage":["https://openalex.org/P4310315671","https://openalex.org/P4310318547"],"host_organization_lineage_names":["Lippincott Williams & Wilkins","Wolters Kluwer"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Clinical Oncology","raw_type":"journal-article"},"volume":null,"type":"conference-abstract","is_traditional":false,"indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5022319770","display_name":"NU Lin","orcid":"https://orcid.org/0000-0003-2263-5413","observed_orcids":["https://orcid.org/0000-0003-2263-5413"]},"institutions":[{"id":"https://openalex.org/I4210117453","display_name":"Dana-Farber Cancer Institute","ror":"https://ror.org/02jzgtq86","country_code":"US","type":"facility","lineage":["https://openalex.org/I4210117453"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Nancy U. Lin","raw_affiliation_strings":["Dana-Farber Cancer Institute, Boston, MA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Dana-Farber Cancer Institute, Boston, MA;","institution_ids":["https://openalex.org/I4210117453"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5080530218","display_name":"Rachel A. Freedman","orcid":"https://orcid.org/0000-0003-0460-674X","observed_orcids":["https://orcid.org/0000-0003-0460-674X"]},"institutions":[{"id":"https://openalex.org/I4210117453","display_name":"Dana-Farber Cancer Institute","ror":"https://ror.org/02jzgtq86","country_code":"US","type":"facility","lineage":["https://openalex.org/I4210117453"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Rachel A. Freedman","raw_affiliation_strings":["Dana-Farber Cancer Institute, Boston, MA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Dana-Farber Cancer Institute, Boston, MA;","institution_ids":["https://openalex.org/I4210117453"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5068666503","display_name":"Kathy D. Miller","orcid":"https://orcid.org/0000-0002-7125-883X","observed_orcids":["https://orcid.org/0000-0002-7125-883X","https://orcid.org/0000-0001-8537-0710"]},"institutions":[{"id":"https://openalex.org/I1283055418","display_name":"Indiana University Health","ror":"https://ror.org/01aaptx40","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1283055418","https://openalex.org/I4388446366","https://openalex.org/I592451"]},{"id":"https://openalex.org/I4388446366","display_name":"Indiana University Indianapolis","ror":"https://ror.org/03eftgw80","country_code":"US","type":"education","lineage":["https://openalex.org/I4388446366","https://openalex.org/I592451"]},{"id":"https://openalex.org/I4390039234","display_name":"Indiana University Melvin and Bren Simon Comprehensive Cancer Center","ror":"https://ror.org/00g1d7b60","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4390039234","https://openalex.org/I592451"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Kathy Miller","raw_affiliation_strings":["Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN;","institution_ids":["https://openalex.org/I1283055418","https://openalex.org/I4388446366","https://openalex.org/I4390039234"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5042743608","display_name":"Komal L. Jhaveri","orcid":"https://orcid.org/0000-0003-0472-1254","observed_orcids":["https://orcid.org/0000-0003-0472-1254"]},"institutions":[{"id":"https://openalex.org/I57206974","display_name":"New York University","ror":"https://ror.org/0190ak572","country_code":"US","type":"education","lineage":["https://openalex.org/I57206974"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Komal L. Jhaveri","raw_affiliation_strings":["New York University Cancer Institute, New York, NY;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"New York University Cancer Institute, New York, NY;","institution_ids":["https://openalex.org/I57206974"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5068366823","display_name":"David A. Eiznhamer","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4387155476","display_name":"Kadmon Corporation (United States)","ror":"https://ror.org/0391bdf37","country_code":"US","type":"company","lineage":["https://openalex.org/I3018075036","https://openalex.org/I4210111804","https://openalex.org/I4387155476"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"David A. Eiznhamer","raw_affiliation_strings":["Kadmon Corporation, New York, NY;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Kadmon Corporation, New York, NY;","institution_ids":["https://openalex.org/I4387155476"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5113624290","display_name":"Mark S. Berger","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4387155476","display_name":"Kadmon Corporation (United States)","ror":"https://ror.org/0391bdf37","country_code":"US","type":"company","lineage":["https://openalex.org/I3018075036","https://openalex.org/I4210111804","https://openalex.org/I4387155476"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Mark S. Berger","raw_affiliation_strings":["Kadmon Corporation, New York, NY;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Kadmon Corporation, New York, NY;","institution_ids":["https://openalex.org/I4387155476"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5003060935","display_name":"Erika Paige Hamilton","orcid":"https://orcid.org/0000-0002-1911-0336","observed_orcids":["https://orcid.org/0000-0002-1911-0336"]},"institutions":[{"id":"https://openalex.org/I4210100810","display_name":"Sarah Cannon","ror":"https://ror.org/014t21j89","country_code":"US","type":"facility","lineage":["https://openalex.org/I4210100810"]},{"id":"https://openalex.org/I4210135086","display_name":"Tennessee Oncology","ror":"https://ror.org/03754ky26","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210135086"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Erika Paige Hamilton","raw_affiliation_strings":["Sarah Cannon Research Institute/Tennessee Oncology, Brentwood, TN;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Sarah Cannon Research Institute/Tennessee Oncology, Brentwood, TN;","institution_ids":["https://openalex.org/I4210100810","https://openalex.org/I4210135086"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":8,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":14,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"34","issue":"15_suppl","first_page":"514","last_page":"514"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10755","display_name":"HER2/EGFR in Cancer Research","score":0.9663000106811523,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10755","display_name":"HER2/EGFR in Cancer Research","score":0.9663000106811523,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10417","display_name":"Lung Cancer Treatments and Mutations","score":0.011699999682605267,"subfield":{"id":"https://openalex.org/subfields/2740","display_name":"Pulmonary and Respiratory Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11600","display_name":"Brain Metastases and Treatment","score":0.006800000090152025,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/trastuzumab","display_name":"trastuzumab","score":0.9700000286102295},{"id":"https://openalex.org/keywords/maximum-tolerated-dose","display_name":"maximum tolerated dose","score":0.8769999742507935},{"id":"https://openalex.org/keywords/her2-positive-breast-cancer","display_name":"HER2-positive breast cancer","score":0.9129999876022339},{"id":"https://openalex.org/keywords/brain-metastases","display_name":"brain metastases","score":0.9610000252723694},{"id":"https://openalex.org/keywords/tyrosine-kinase-inhibitors","display_name":"tyrosine kinase inhibitors","score":0.7570000290870667},{"id":"https://openalex.org/keywords/blood-brain-barrier-penetration","display_name":"blood-brain barrier penetration","score":0.9110000133514404},{"id":"https://openalex.org/keywords/egfr-inhibition","display_name":"EGFR inhibition","score":0.7429999709129333},{"id":"https://openalex.org/keywords/dose-limiting-toxicity","display_name":"dose-limiting toxicity","score":0.7419999837875366},{"id":"https://openalex.org/keywords/diarrhea","display_name":"diarrhea","score":0.9309999942779541},{"id":"https://openalex.org/keywords/qtc-prolongation","display_name":"QTc prolongation","score":0.996999979019165},{"id":"https://openalex.org/keywords/combination-therapy","display_name":"combination therapy","score":0.6890000104904175},{"id":"https://openalex.org/keywords/dose-escalation","display_name":"dose escalation","score":0.6809999942779541},{"id":"https://openalex.org/keywords/metastatic-breast-cancer","display_name":"metastatic breast cancer","score":0.6660000085830688},{"id":"https://openalex.org/keywords/adverse-events","display_name":"adverse events","score":0.6399999856948853},{"id":"https://openalex.org/keywords/plasma-drug-concentration","display_name":"plasma drug concentration","score":0.5830000042915344}],"concepts":[{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.9058136940002441},{"id":"https://openalex.org/C2778375690","wikidata":"https://www.wikidata.org/wiki/Q7814214","display_name":"Tolerability","level":3,"score":0.7146106958389282},{"id":"https://openalex.org/C2778570526","wikidata":"https://www.wikidata.org/wiki/Q653197","display_name":"Rash","level":2,"score":0.7059329152107239},{"id":"https://openalex.org/C2777288759","wikidata":"https://www.wikidata.org/wiki/Q4164182","display_name":"Dosing","level":2,"score":0.6661956906318665},{"id":"https://openalex.org/C2779786085","wikidata":"https://www.wikidata.org/wiki/Q412616","display_name":"Trastuzumab","level":4,"score":0.6579555869102478},{"id":"https://openalex.org/C72563966","wikidata":"https://www.wikidata.org/wiki/Q1303415","display_name":"Cohort","level":2,"score":0.6297585964202881},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.5826069712638855},{"id":"https://openalex.org/C2780580376","wikidata":"https://www.wikidata.org/wiki/Q186889","display_name":"Nausea","level":2,"score":0.5447607040405273},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.5089883804321289},{"id":"https://openalex.org/C112705442","wikidata":"https://www.wikidata.org/wiki/Q323936","display_name":"Pharmacokinetics","level":2,"score":0.5020797252655029},{"id":"https://openalex.org/C2778820342","wikidata":"https://www.wikidata.org/wiki/Q906415","display_name":"Tyrosine-kinase inhibitor","level":3,"score":0.489805668592453},{"id":"https://openalex.org/C90924648","wikidata":"https://www.wikidata.org/wiki/Q120569","display_name":"Gastroenterology","level":1,"score":0.45530739426612854},{"id":"https://openalex.org/C197934379","wikidata":"https://www.wikidata.org/wiki/Q2047938","display_name":"Adverse effect","level":2,"score":0.4539565443992615},{"id":"https://openalex.org/C530470458","wikidata":"https://www.wikidata.org/wiki/Q128581","display_name":"Breast cancer","level":3,"score":0.4469899535179138},{"id":"https://openalex.org/C2775930923","wikidata":"https://www.wikidata.org/wiki/Q12859063","display_name":"Metastatic breast cancer","level":4,"score":0.43671682476997375},{"id":"https://openalex.org/C22979827","wikidata":"https://www.wikidata.org/wiki/Q5137311","display_name":"Cmax","level":3,"score":0.42941349744796753},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.4041096568107605}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1200/jco.2016.34.15_suppl.514","doi":"https://doi.org/10.1200/jco.2016.34.15_suppl.514","is_oa":false,"landing_page_url":"https://doi.org/10.1200/jco.2016.34.15_suppl.514","pdf_url":null,"source":{"id":"https://openalex.org/S15137598","display_name":"Journal of Clinical Oncology","issn_l":"0732-183X","issn":["0732-183X","1527-7755"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310315671","host_organization_name":"Lippincott Williams & Wilkins","host_organization_lineage":["https://openalex.org/P4310315671","https://openalex.org/P4310318547"],"host_organization_lineage_names":["Lippincott Williams & Wilkins","Wolters Kluwer"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Clinical Oncology","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"score":1.0,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2591496638","https://openalex.org/W3027738480","https://openalex.org/W4400523607","https://openalex.org/W4410608437","https://openalex.org/W2803163286","https://openalex.org/W4386538570","https://openalex.org/W2716808802","https://openalex.org/W3013480162","https://openalex.org/W2810342468","https://openalex.org/W3167499853"],"abstract_inverted_index":{"514":[0],"Background:":[1],"Brain":[2],"metastases":[3,257],"(BM)":[4,258],"are":[5],"common":[6,229],"in":[7,46,67,160,192,217,308],"patients":[8,315],"(pts)":[9],"with":[10,73,86,146,248,255,303,316],"HER2+":[11,68,309],"BC":[12,69,310],"and":[13,26,36,40,50,109,124,130,172,206,239,275],"there":[14],"is":[15,31,305],"a":[16,19,32,167,213],"need":[17],"for":[18,272,290],"potent":[20,33],"TKI":[21],"that":[22],"crosses":[23],"the":[24,44,63,104,119,131,134,149,161,179,193,218,306],"BBB":[25,45],"penetrates":[27],"CNS":[28,52],"tissues.":[29],"Tesevatinib":[30],"EGFR":[34],"inhibitor":[35],"also":[37],"inhibits":[38],"HER2":[39],"SRC":[41],"while":[42],"crossing":[43],"whole":[47],"animal":[48],"models":[49],"achieving":[51],"levels":[53],"similar":[54],"to":[55,202,246,264,284],"plasma.":[56],"Methods:":[57],"This":[58],"dose":[59,298],"escalation":[60],"study":[61],"defined":[62],"MTD":[64,307],"of":[65,106,121,133,212,215,251,299,313],"tesevatinib":[66,87,300],"pts":[70,139,159,183,191],"when":[71],"combined":[72],"trastuzumab":[74],"6":[75,291],"mg/kg":[76],"IV":[77],"every":[78],"3":[79,138,170,174,225,340,349,356,359],"weeks.":[80],"A":[81,294],"3+3":[82],"design":[83],"was":[84,154],"utilized":[85],"given":[88],"150":[89,107,334],"mg,":[90,92,94],"250":[91,110,265,339],"300":[93,122,143,187,195,219,260,285,295,344],"or":[95],"350":[96,125,150,162,280,351],"mg":[97,108,111,123,126,144,151,163,188,196,220,261,266,281,286,296],"daily":[98,297],"(QD).":[99],"Previously":[100],"reported":[101],"results":[102,120],"demonstrated":[103],"tolerability":[105],"QD":[112,127,145,152,197,221,262,282],"dosing":[113,128,200],"(ASCO":[114],"2015).":[115],"Here":[116],"we":[117],"report":[118],"cohorts,":[129],"establishment":[132],"MTD.":[135],"Results:":[136],"After":[137],"were":[140,184,207,234],"treated":[141],"at":[142,186],"no":[147],"DLTs,":[148],"cohort":[153,164,198,222],"initiated.":[155],"The":[156,227],"first":[157],"2":[158,352],"each":[165],"experienced":[166,223],"DLT":[168,332],"(Grade":[169],"diarrhea":[171],"Grade":[173,224],"QTc":[175,360],"prolongation).":[176],"To":[177],"confirm":[178],"MTD,":[180],"5":[181],"additional":[182,194],"enrolled":[185],"QD.":[189],"Two":[190,312],"discontinued":[199],"prior":[201],"completing":[203],"21":[204],"days":[205],"replaced.":[208],"One":[209,253],"pt":[210,254],"out":[211],"total":[214],"8":[216,345],"diarrhea.":[226],"most":[228],"AE\u2019s":[230],"(":[231],">":[232],"30%)":[233],"rash,":[235],"diarrhea,":[236],"decreased":[237],"appetite,":[238],"nausea.":[240],"AE":[241],"incidence":[242],"did":[243],"not":[244],"appear":[245],"correlate":[247],"plasma":[249],"concentration":[250],"drug.":[252],"brain":[256],"on":[259,279],"(reduced":[263,283],"QD)":[267,287],"had":[268,288,318],"stable":[269,320],"disease":[270],"(SD)":[271],"7":[273],"months":[274],"another":[276],"BM":[277,317],"patient":[278],"SD":[289],"months.":[292],"Conclusions:":[293],"(in":[301],"combination":[302],"trastuzumab)":[304],"patients.":[311],"seven":[314],"prolonged":[319],"disease.":[321],"Clinical":[322],"trial":[323],"information:":[324],"NCT02154529.Tesevatinib":[325],"Dose":[326],"#":[327],"Patients":[328],"Median":[329],"Age":[330],"(Range)":[331],"Events":[333],"4":[335],"43":[336],"(29-48)":[337],"-":[338,343],"54":[341],"(42-55)":[342],"50":[346],"(40-61)":[347],"Gr":[348,355,358],"Diarrhea":[350],"60":[353],"(58-61)":[354],"Diarrhea,":[357],"Total":[361],"17":[362],"48":[363],"(29-61)":[364]},"counts_by_year":[{"year":2025,"cited_by_count":1},{"year":2022,"cited_by_count":1},{"year":2021,"cited_by_count":2},{"year":2020,"cited_by_count":2},{"year":2019,"cited_by_count":2},{"year":2018,"cited_by_count":2},{"year":2017,"cited_by_count":3},{"year":2016,"cited_by_count":1}],"updated_date":"2026-10-27T15:51:10.671819","created_date":"2017-07-21T00:00:00"}
