Trastuzumab Emtansine Plus Non-Pegylated Liposomal Doxorubicin in HER2-Positive Metastatic Breast Cancer (Thelma): A Single-Arm, Multicenter, Phase Ib Trial

The paper assesses the dose-limiting toxicities and the maximum tolerated dose (MTD) of trastuzumab emtansine (T-DM1) combined with non-pegylated liposomal doxorubicin (NPLD) in HER2-positive (HER2+) metastatic breast cancer (MBC). This single-arm, open-label, phase Ib trial (NCT02562378) enrolled a...

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Autores: López Miranda, Elena, Pérez García, José Manuel, Di Cosimo, Serena, Brain, Etienne, Ravnik, Maja, Escrivá de Romaní, Santiago, Vidal Losada, Maria Jesús, Gligorov, Joseph, Borstnar, Simona, Calabuig, Laura, Sampayo Cordero, Miguel, Malfettone, Andrea, Llombart Cussac, Antonio, Suter, Thomas M., Cortés, Javier
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/176420
Acceso en línea:https://hdl.handle.net/2445/176420
Access Level:acceso abierto
Palabra clave:Càncer de mama
Metàstasi
Breast cancer
Metastasis
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spelling Trastuzumab Emtansine Plus Non-Pegylated Liposomal Doxorubicin in HER2-Positive Metastatic Breast Cancer (Thelma): A Single-Arm, Multicenter, Phase Ib TrialLópez Miranda, ElenaPérez García, José ManuelDi Cosimo, SerenaBrain, EtienneRavnik, MajaEscrivá de Romaní, SantiagoVidal Losada, Maria JesúsGligorov, JosephBorstnar, SimonaCalabuig, LauraSampayo Cordero, MiguelMalfettone, AndreaLlombart Cussac, AntonioSuter, Thomas M.Cortés, JavierCàncer de mamaMetàstasiBreast cancerMetastasisThe paper assesses the dose-limiting toxicities and the maximum tolerated dose (MTD) of trastuzumab emtansine (T-DM1) combined with non-pegylated liposomal doxorubicin (NPLD) in HER2-positive (HER2+) metastatic breast cancer (MBC). This single-arm, open-label, phase Ib trial (NCT02562378) enrolled anthracycline-naïve HER2+ MBC patients who had progressed on trastuzumab and taxanes. Patients received a maximum of 6 cycles of NPLD intravenously (IV) at various dose levels (45, 50, and 60 mg/m2) in the "3 plus 3" dose-escalation part. During expansion, they received 60 mg/m2 of NPLD every 3 weeks (Q3W) plus standard doses of T-DM1. The MTD was T-DM1 3.6 mg/kg plus NPLD 60 mg/m2 administered IV Q3W. No clinically relevant worsening of cardiac function was observed. Among all evaluable patients, the overall response rate was 40.0% (95%CI, 16.3-67.7) with a median duration of response of 6.9 months (95%CI, 4.8-9.1). Clinical benefit rate was 66.7% (95%CI, 38.4-88.2) and median progression-free survival was 7.2 months (95%CI, 4.5-9.6). No significant influence of NPLD on T-DM1 pharmacokinetics was observed. The addition of NPLD to T-DM1 is feasible but does not seem to improve the antitumor efficacy of T-DM1 in HER2+ MBC patients.MDPI2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/176420Articles publicats en revistes (Medicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3390/cancers12123509Cancers, 2020, vol. 12, num. 12https://doi.org/10.3390/cancers12123509cc-by (c) López Miranda, Elena et al., 2020http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1764202026-05-27T06:46:51Z
dc.title.none.fl_str_mv Trastuzumab Emtansine Plus Non-Pegylated Liposomal Doxorubicin in HER2-Positive Metastatic Breast Cancer (Thelma): A Single-Arm, Multicenter, Phase Ib Trial
title Trastuzumab Emtansine Plus Non-Pegylated Liposomal Doxorubicin in HER2-Positive Metastatic Breast Cancer (Thelma): A Single-Arm, Multicenter, Phase Ib Trial
spellingShingle Trastuzumab Emtansine Plus Non-Pegylated Liposomal Doxorubicin in HER2-Positive Metastatic Breast Cancer (Thelma): A Single-Arm, Multicenter, Phase Ib Trial
López Miranda, Elena
Càncer de mama
Metàstasi
Breast cancer
Metastasis
title_short Trastuzumab Emtansine Plus Non-Pegylated Liposomal Doxorubicin in HER2-Positive Metastatic Breast Cancer (Thelma): A Single-Arm, Multicenter, Phase Ib Trial
title_full Trastuzumab Emtansine Plus Non-Pegylated Liposomal Doxorubicin in HER2-Positive Metastatic Breast Cancer (Thelma): A Single-Arm, Multicenter, Phase Ib Trial
title_fullStr Trastuzumab Emtansine Plus Non-Pegylated Liposomal Doxorubicin in HER2-Positive Metastatic Breast Cancer (Thelma): A Single-Arm, Multicenter, Phase Ib Trial
title_full_unstemmed Trastuzumab Emtansine Plus Non-Pegylated Liposomal Doxorubicin in HER2-Positive Metastatic Breast Cancer (Thelma): A Single-Arm, Multicenter, Phase Ib Trial
title_sort Trastuzumab Emtansine Plus Non-Pegylated Liposomal Doxorubicin in HER2-Positive Metastatic Breast Cancer (Thelma): A Single-Arm, Multicenter, Phase Ib Trial
dc.creator.none.fl_str_mv López Miranda, Elena
Pérez García, José Manuel
Di Cosimo, Serena
Brain, Etienne
Ravnik, Maja
Escrivá de Romaní, Santiago
Vidal Losada, Maria Jesús
Gligorov, Joseph
Borstnar, Simona
Calabuig, Laura
Sampayo Cordero, Miguel
Malfettone, Andrea
Llombart Cussac, Antonio
Suter, Thomas M.
Cortés, Javier
author López Miranda, Elena
author_facet López Miranda, Elena
Pérez García, José Manuel
Di Cosimo, Serena
Brain, Etienne
Ravnik, Maja
Escrivá de Romaní, Santiago
Vidal Losada, Maria Jesús
Gligorov, Joseph
Borstnar, Simona
Calabuig, Laura
Sampayo Cordero, Miguel
Malfettone, Andrea
Llombart Cussac, Antonio
Suter, Thomas M.
Cortés, Javier
author_role author
author2 Pérez García, José Manuel
Di Cosimo, Serena
Brain, Etienne
Ravnik, Maja
Escrivá de Romaní, Santiago
Vidal Losada, Maria Jesús
Gligorov, Joseph
Borstnar, Simona
Calabuig, Laura
Sampayo Cordero, Miguel
Malfettone, Andrea
Llombart Cussac, Antonio
Suter, Thomas M.
Cortés, Javier
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer de mama
Metàstasi
Breast cancer
Metastasis
topic Càncer de mama
Metàstasi
Breast cancer
Metastasis
description The paper assesses the dose-limiting toxicities and the maximum tolerated dose (MTD) of trastuzumab emtansine (T-DM1) combined with non-pegylated liposomal doxorubicin (NPLD) in HER2-positive (HER2+) metastatic breast cancer (MBC). This single-arm, open-label, phase Ib trial (NCT02562378) enrolled anthracycline-naïve HER2+ MBC patients who had progressed on trastuzumab and taxanes. Patients received a maximum of 6 cycles of NPLD intravenously (IV) at various dose levels (45, 50, and 60 mg/m2) in the "3 plus 3" dose-escalation part. During expansion, they received 60 mg/m2 of NPLD every 3 weeks (Q3W) plus standard doses of T-DM1. The MTD was T-DM1 3.6 mg/kg plus NPLD 60 mg/m2 administered IV Q3W. No clinically relevant worsening of cardiac function was observed. Among all evaluable patients, the overall response rate was 40.0% (95%CI, 16.3-67.7) with a median duration of response of 6.9 months (95%CI, 4.8-9.1). Clinical benefit rate was 66.7% (95%CI, 38.4-88.2) and median progression-free survival was 7.2 months (95%CI, 4.5-9.6). No significant influence of NPLD on T-DM1 pharmacokinetics was observed. The addition of NPLD to T-DM1 is feasible but does not seem to improve the antitumor efficacy of T-DM1 in HER2+ MBC patients.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/176420
url https://hdl.handle.net/2445/176420
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3390/cancers12123509
Cancers, 2020, vol. 12, num. 12
https://doi.org/10.3390/cancers12123509
dc.rights.none.fl_str_mv cc-by (c) López Miranda, Elena et al., 2020
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) López Miranda, Elena et al., 2020
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Articles publicats en revistes (Medicina)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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