Trastuzumab deruxtecan in patients with previously treated HER2-low advanced breast cancer and active brain metastases: the DEBBRAH trial

Background: Trastuzumab deruxtecan (T-DXd) is approved for human epidermal growth factor receptor 2 (HER2)positive and HER2-low advanced breast cancer (ABC). T-DXd has shown encouraging intracranial activity in HER2positive ABC patients with stable or active brain metastases (BMs); however, its effi...

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Autores: Vaz Batista M, Pérez-García JM, Cortez P, Garrigós L, Fernández-Abad M, Gion M, Martínez-Bueno A, Saavedra C, Teruel I, Fernandez-Ortega A, Servitja S, Ruiz-Borrego M, de la Haba-Rodríguez J, Martrat G, Pérez-Escuredo J, Alcalá-López D, Sampayo-Cordero M, Braga S, Cortés J, Llombart-Cussac A
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Repositorio:r-FISABIO. Repositorio Institucional de Producción Científica
OAI Identifier:oai:fisabio.fundanetsuite.com:p17664
Acceso en línea:https://fisabio.portalinvestigacion.com/publicaciones/17664
Access Level:acceso abierto
Palabra clave:advanced breast cancer
active brain metastases
HER2-low
T-DXd
trastuzumab deruxtecan
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spelling Trastuzumab deruxtecan in patients with previously treated HER2-low advanced breast cancer and active brain metastases: the DEBBRAH trialVaz Batista MPérez-García JMCortez PGarrigós LFernández-Abad MGion MMartínez-Bueno ASaavedra CTeruel IFernandez-Ortega AServitja SRuiz-Borrego Mde la Haba-Rodríguez JMartrat GPérez-Escuredo JAlcalá-López DSampayo-Cordero MBraga SCortés JLlombart-Cussac Aadvanced breast canceractive brain metastasesHER2-lowT-DXdtrastuzumab deruxtecanBackground: Trastuzumab deruxtecan (T-DXd) is approved for human epidermal growth factor receptor 2 (HER2)positive and HER2-low advanced breast cancer (ABC). T-DXd has shown encouraging intracranial activity in HER2positive ABC patients with stable or active brain metastases (BMs); however, its efficacy fi cacy in patients with HER2-low ABC with BMs is not well established yet. Methods: DEBBRAH is a single-arm, fi ve-cohort, phase II study evaluating T-DXd in patients with central nervous system involvement from HER2-positive and HER2-low ABC. Here, we report results from patients with heavily pretreated HER2-low ABC and active BMs, enrolled in cohorts 2 (n n = 6, asymptomatic untreated BMs) and 4 (n n = 6, progressing BMs after local therapy). Patients received 5.4 mg/kg T-DXd intravenously once every 21 days. The primary endpoint was intracranial objective response rate per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) for both cohorts. Results: Intracranial objective response rate per RANO-BM was 50.0% [3/6 patients; 95% confidence fi dence interval (CI) 11.8% to 88.2%] and 33.3% [2/6 patients; 95% CI 4.3% to 77.7%; P = 0.033 (one-sided)] in cohorts 2 and 4, respectively. All responders had partial responses. Median time to intracranial response was 2.3 months (range, 1.5-4.0 months) and median duration of intracranial response was 7.2 months (range, 2.8-16.8 months). Median progression-free survival per RECIST v.1.1. was 5.4 months (95% CI 4.1-10.0 months). Treatment-emergent adverse events occurred in all patients included (16.7% grade 3). Three patients (25.0%) had grade 1 interstitial lung disease/pneumonitis. Conclusions: T-DXd demonstrated promising intracranial activity in pretreated HER2-low ABC patients with active BMs. Further studies are needed to validate these results in larger cohorts. This trial is registered with ClinicalTrials.gov, NCT04420598.ELSEVIER2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fisabio.portalinvestigacion.com/publicaciones/17664ESMO OpenISSN: 20597029reponame:r-FISABIO. Repositorio Institucional de Producción Científicainstname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)Inglésinfo:eu-repo/semantics/openAccessoai:fisabio.fundanetsuite.com:p176642026-06-11T12:45:17Z
dc.title.none.fl_str_mv Trastuzumab deruxtecan in patients with previously treated HER2-low advanced breast cancer and active brain metastases: the DEBBRAH trial
title Trastuzumab deruxtecan in patients with previously treated HER2-low advanced breast cancer and active brain metastases: the DEBBRAH trial
spellingShingle Trastuzumab deruxtecan in patients with previously treated HER2-low advanced breast cancer and active brain metastases: the DEBBRAH trial
Vaz Batista M
advanced breast cancer
active brain metastases
HER2-low
T-DXd
trastuzumab deruxtecan
title_short Trastuzumab deruxtecan in patients with previously treated HER2-low advanced breast cancer and active brain metastases: the DEBBRAH trial
title_full Trastuzumab deruxtecan in patients with previously treated HER2-low advanced breast cancer and active brain metastases: the DEBBRAH trial
title_fullStr Trastuzumab deruxtecan in patients with previously treated HER2-low advanced breast cancer and active brain metastases: the DEBBRAH trial
title_full_unstemmed Trastuzumab deruxtecan in patients with previously treated HER2-low advanced breast cancer and active brain metastases: the DEBBRAH trial
title_sort Trastuzumab deruxtecan in patients with previously treated HER2-low advanced breast cancer and active brain metastases: the DEBBRAH trial
dc.creator.none.fl_str_mv Vaz Batista M
Pérez-García JM
Cortez P
Garrigós L
Fernández-Abad M
Gion M
Martínez-Bueno A
Saavedra C
Teruel I
Fernandez-Ortega A
Servitja S
Ruiz-Borrego M
de la Haba-Rodríguez J
Martrat G
Pérez-Escuredo J
Alcalá-López D
Sampayo-Cordero M
Braga S
Cortés J
Llombart-Cussac A
author Vaz Batista M
author_facet Vaz Batista M
Pérez-García JM
Cortez P
Garrigós L
Fernández-Abad M
Gion M
Martínez-Bueno A
Saavedra C
Teruel I
Fernandez-Ortega A
Servitja S
Ruiz-Borrego M
de la Haba-Rodríguez J
Martrat G
Pérez-Escuredo J
Alcalá-López D
Sampayo-Cordero M
Braga S
Cortés J
Llombart-Cussac A
author_role author
author2 Pérez-García JM
Cortez P
Garrigós L
Fernández-Abad M
Gion M
Martínez-Bueno A
Saavedra C
Teruel I
Fernandez-Ortega A
Servitja S
Ruiz-Borrego M
de la Haba-Rodríguez J
Martrat G
Pérez-Escuredo J
Alcalá-López D
Sampayo-Cordero M
Braga S
Cortés J
Llombart-Cussac A
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv advanced breast cancer
active brain metastases
HER2-low
T-DXd
trastuzumab deruxtecan
topic advanced breast cancer
active brain metastases
HER2-low
T-DXd
trastuzumab deruxtecan
description Background: Trastuzumab deruxtecan (T-DXd) is approved for human epidermal growth factor receptor 2 (HER2)positive and HER2-low advanced breast cancer (ABC). T-DXd has shown encouraging intracranial activity in HER2positive ABC patients with stable or active brain metastases (BMs); however, its efficacy fi cacy in patients with HER2-low ABC with BMs is not well established yet. Methods: DEBBRAH is a single-arm, fi ve-cohort, phase II study evaluating T-DXd in patients with central nervous system involvement from HER2-positive and HER2-low ABC. Here, we report results from patients with heavily pretreated HER2-low ABC and active BMs, enrolled in cohorts 2 (n n = 6, asymptomatic untreated BMs) and 4 (n n = 6, progressing BMs after local therapy). Patients received 5.4 mg/kg T-DXd intravenously once every 21 days. The primary endpoint was intracranial objective response rate per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) for both cohorts. Results: Intracranial objective response rate per RANO-BM was 50.0% [3/6 patients; 95% confidence fi dence interval (CI) 11.8% to 88.2%] and 33.3% [2/6 patients; 95% CI 4.3% to 77.7%; P = 0.033 (one-sided)] in cohorts 2 and 4, respectively. All responders had partial responses. Median time to intracranial response was 2.3 months (range, 1.5-4.0 months) and median duration of intracranial response was 7.2 months (range, 2.8-16.8 months). Median progression-free survival per RECIST v.1.1. was 5.4 months (95% CI 4.1-10.0 months). Treatment-emergent adverse events occurred in all patients included (16.7% grade 3). Three patients (25.0%) had grade 1 interstitial lung disease/pneumonitis. Conclusions: T-DXd demonstrated promising intracranial activity in pretreated HER2-low ABC patients with active BMs. Further studies are needed to validate these results in larger cohorts. This trial is registered with ClinicalTrials.gov, NCT04420598.
publishDate 2024
dc.date.none.fl_str_mv 2024
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://fisabio.portalinvestigacion.com/publicaciones/17664
url https://fisabio.portalinvestigacion.com/publicaciones/17664
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv ELSEVIER
publisher.none.fl_str_mv ELSEVIER
dc.source.none.fl_str_mv ESMO Open
ISSN: 20597029
reponame:r-FISABIO. Repositorio Institucional de Producción Científica
instname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
instname_str Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
reponame_str r-FISABIO. Repositorio Institucional de Producción Científica
collection r-FISABIO. Repositorio Institucional de Producción Científica
repository.name.fl_str_mv
repository.mail.fl_str_mv
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