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

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 canc...

Descripción completa

Detalles Bibliográficos
Autores: Gavila, Joaquin, Oliveira, Mafalda, Pascual, Tomas, Perez-Garcia, Jose, Gonzalez, Xavier, Canes, Jordi, Pare, Laia, Calvo, Isabel, Ciruelos, Eva, Munoz, Montserrat, Virizuela, Juan A, Ruiz, Isabel, Andres, Raquel, Perello Martorell, Antonia, Martinez, Jeronimo, Morales, Serafin, Marin-Aguilera, Mercedes, Martinez, Debora, Quero, Juan C, Llombart-Cussac, Antonio, Prat, Aleix
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/22652
Acceso en línea:https://hdl.handle.net/20.500.12105/22652
Access Level:acceso abierto
Palabra clave:Breast cancer
PAM50
HER2
Intrinsic subtypes
Cardiac safety
HER2-enriched
Neoadjuvant
Cardiotoxicidad
Polietilenglicoles
Paclitaxel
Femenino
Receptor ErbB-2
Anticuerpos Monoclonales Humanizados
Terapia Neoadyuvante
Trastuzumab
Humanos
Persona de Mediana Edad
Protocolos de Quimioterapia Combinada Antineoplásica
Anciano
Doxorrubicina
Neoplasias de la Mama
Adulto
Quimioterapia Adyuvante
Breast Neoplasms
Aged
Doxorubicin
Neoadjuvant Therapy
Polyethylene Glycols
Adult
Humans
Antibodies, Monoclonal, Humanized
Cardiotoxicity
Antineoplastic Combined Chemotherapy Protocols
Middle Aged
Receptor, ErbB-2
Female
Chemotherapy, Adjuvant
Descripción
Sumario: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.

Similares en LA Referencia