Safety, activity, and molecular heterogeneity following neoadjuvant non-pegylated liposomal doxorubicin, paclitaxel, trastuzumab, and pertuzumab in HER2-positive breast cancer (Opti-HER HEART): an open-label, single-group, multicenter, phase 2 trial

Autor: Mafalda Oliveira, Serafin Morales, Jerónimo Martínez, Raquel Andrés, Juan C. Quero, Antonio Llombart-Cussac, Antonia Perelló, Aleix Prat, Mercedes Marín-Aguilera, Eva Ciruelos, Joaquín Gavilá, Tomás Pascual, Laia Paré, Isabel Ruiz, Isabel Calvo, Juan Antonio Virizuela, Montserrat Muñoz, Jordi Canes, D. Martinez, Xavier Gonzalez, Jose Perez-Garcia
Přispěvatelé: Institut Català de la Salut, [Gavilá J] Fundación Instituto Valenciano de Oncología, Valencia, Spain. [Oliveira M] Hospital Universitari Vall d'Hebron, Barcelona, Spain. Vall d'Hebron Institut d'Oncologia, Barcelona, Spain. [Pascual T] August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain. Hospital Clínic, Barcelona, Spain. SOLTI Breast Cancer Research Group, Barcelona, Spain. [Perez-Garcia J] Hospital Universitari Vall d'Hebron, Barcelona, Spain. Vall d'Hebron Institut d'Oncologia, Barcelona, Spain. Instituto Oncológico Baselga, Hospital Quirón, Barcelona, Spain. [Gonzàlez X] SOLTI Breast Cancer Research Group, Barcelona, Spain. Institut Oncològic Rosell, Hospital General Catalunya, Barcelona, Spain. [Canes J] SOLTI Breast Cancer Research Group, Barcelona, Spain., Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus
Rok vydání: 2019
Předmět:
glicoles de polietileno
Oncology
Receptor
ErbB-2
medicine.medical_treatment
Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES]
neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES]
humanos
lcsh:Medicine
neoplasias de la mama
Insuficiència cardíaca
Other subheadings::Other subheadings::/drug therapy [Other subheadings]
Otros calificadores::Otros calificadores::/efectos adversos [Otros calificadores]
Polyethylene Glycols
chemistry.chemical_compound
0302 clinical medicine
Breast cancer
Mama - Càncer
Trastuzumab
Antineoplastic Combined Chemotherapy Protocols
Clinical endpoint
030212 general & internal medicine
PAM50
intrinsic subtypes
Características de los Estudios::Estudio Clínico::Ensayo Clínico [CARACTERÍSTICAS DE PUBLICACIONES]
skin and connective tissue diseases
mediana edad
Neoadjuvant therapy
Otros calificadores::Otros calificadores::/tratamiento farmacológico [Otros calificadores]
anciano
Therapeutics::Combined Modality Therapy::Neoadjuvant Therapy [ANALYTICAL
DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT]
Ejection fraction
protocolos de quimioterapia antineoplásica combinada
General Medicine
Middle Aged
adulto
Neoadjuvant Therapy
Paclitaxel
Chemotherapy
Adjuvant
Female
Pertuzumab
Research Article
medicine.drug
Adult
medicine.medical_specialty
doxorrubicina
Heart failure
Breast Neoplasms
Antibodies
Monoclonal
Humanized
Antibodies
Càncer de mama
03 medical and health sciences
características del estudio::estudio clínico::ensayo clínico [CARACTERÍSTICAS DE PUBLICACIONES]
Internal medicine
Study Characteristics::Clinical Study::Clinical Trial [PUBLICATION CHARACTERISTICS]
HER2
medicine
Other subheadings::Other subheadings::/adverse effects [Other subheadings]
Humans
Càncer - Quimioteràpia - Complicacions
Aged
Terapéutica::Terapia Combinada::Terapia Neoadyuvante [TÉCNICAS Y EQUIPOS ANALÍTICOS
DIAGNÓSTICOS Y TERAPÉUTICOS]
tratamiento neoadyuvante
business.industry
neoadjuvant
lcsh:R
Odds ratio
Neoplasias::Neoplasias por Localización::Neoplasias de la Mama [ENFERMEDADES]
medicine.disease
Cardiotoxicity
chemistry
Doxorubicin
anticuerpos
HER2-enriched
terapéutica::tratamiento combinado::tratamiento neoadyuvante [TÉCNICAS Y EQUIPOS ANALÍTICOS
DIAGNÓSTICOS Y TERAPÉUTICOS]
cardiac safety
business
030217 neurology & neurosurgery
Assaigs clínics
Zdroj: BMC MEDICINE
r-FISABIO. Repositorio Institucional de Producción Científica
instname
Zaguán. Repositorio Digital de la Universidad de Zaragoza
r-FISABIO: Repositorio Institucional de Producción Científica
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Scientia
Recercat: Dipósit de la Recerca de Catalunya
Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
BMC Medicine, Vol 17, Iss 1, Pp 1-12 (2019)
Dipòsit Digital de la UB
Universidad de Barcelona
Recercat. Dipósit de la Recerca de Catalunya
BMC Medicine
ISSN: 1741-7015
Popis: BackgroundThe Opti-HER HEART trial aimed to optimize activity while minimizing cardiac risk by combining trastuzumab, pertuzumab, and paclitaxel with non-pegylated liposomal doxorubicin in the treatment of HER2-positive early breast cancer.MethodsPatients with stage II-IIIB HER2-positive breast cancer received neoadjuvant trastuzumab, pertuzumab, paclitaxel, and a non-pegylated liposomal doxorubicin every three weeks for six cycles. The primary endpoint was cardiac safety during neoadjuvant therapy. Type A (symptomatic congestive heart failure) and B (asymptomatic reduction of left ventricular ejection fraction) cardiac events were evaluated. Secondary endpoints included the evaluation of the pathological complete response (pCR) rate and overall response rate, among others. As an ad-hoc exploratory analysis, the expression of 55 breast cancer-related genes, including the PAM50 genes, was measured in 58 baseline tumor samples and 60 surgical specimens.ResultsEighty-three patients were recruited. The incidence of cardiac events during neoadjuvant treatment was 2.4%. No type A cardiac event was observed. The overall pCR rate was 56.6% (95% confidence interval (CI) 45.3-67.5%). The HER2-enriched subtype, which represented 52.0% of all baseline samples, was associated with a higher pCR rate compared to non-HER2-enriched tumors (83.3% vs. 46.3%; odds ratio 5.76, 95% CI 1.71-19.42). The association of subtype with pCR was independent of known clinicopathological variables, including hormone receptor status. Compared to baseline samples, surgical specimens showed a significant downregulation of proliferation-related genes (MKI67 and CCNB1) and ERBB2 levels, and a significant upregulation of luminal-related (ESR1 and PGR) and immune (CD8A) genes.ConclusionsThe combination of dual HER2 blockade with trastuzumab and pertuzumab with paclitaxel and non-pegylated liposomal doxorubicin is associated with a low rate of cardiac events. The HER2-enriched subtype is associated with a high rate of pCR.
This study was supported by a grant from TEVA. Trastuzumab and pertuzumab were kindly provided by Roche and non-pegylated liposomal doxorubicin by TEVA. This study was funded, in part, by an unrestricted grant from Roche, Pas a Pas, Save the Mama, Instituto de Salud Carlos III (ISCIII) through the Plan Estatal de Investigacion Cientifica y Tecnica y de Innovacion 2013-2016 (PI16/00904) (AP). TEVA and Roche had no role in the management of this trial. The decisions and responsibilities of this trial were all under the sponsor: SOLTI Group.
Databáze: OpenAIRE
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