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

Gavilá, J. ; Oliveira, M. ; Pascual, T. ; Perez-Garcia, J. ; Gonzàlez, X. ; Canes, J. ; Paré, L. ; Calvo, I. ; Ciruelos, E. ; Muñoz, M. ; Virizuela, J.A. ; Ruiz, I. ; Andrés, R. (Universidad de Zaragoza) ; Perelló, A. ; Martínez, J. ; Morales, S. ; Marín-Aguilera, M. ; Martínez, D. ; Quero, J.C. ; Llombart-Cussac, A. ; Prat, A.

Resumen: Background: The Opti-HER HEART trial aimed to optimize activity while minimizing cardiac risk by combiningtrastuzumab, pertuzumab, and paclitaxel with non-pegylated liposomal doxorubicin in the treatment of HER2-positive early breast cancer.
Methods: Patients with stage II–IIIB HER2-positive breast cancer received neoadjuvant trastuzumab, pertuzumab, paclitaxel, and a non-pegylated liposomal doxorubicinevery three weeks for six cycles. The primary endpoint wascardiac safety during neoadjuvant therapy. Type A (symptomatic congestive heart failure) and B (asymptomaticreduction of left ventricular ejection fraction) cardiacevents were evaluated. Secondary endpoints included theevaluation of the pathological complete response (pCR) rate and overall response rate, among others. As anad-hoc exploratory analysis, the expression of 55 breast cancer-related genes, including thePAM50genes, wasmeasured in 58 baseline tumor samples and 60 surgical specimens.
Results: Eighty-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% ofall baseline samples, was associated with a higher pCRrate compared to non-HER2-enriched tumors (83.3% vs. 46.3%; odds ratio 5.76, 95% CI 1.71–19.42). The association ofsubtype 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(MKI67andCCNB1)andERBB2levels, and a significant upregulation of luminal-related (ESR1andPGR)andimmune(CD8A)genes.
Conclusions: The combination of dual HER2 blockade with trastuzumab and pertuzumab with paclitaxel andnon-pegylated liposomal doxorubicin is associated with a low rate of cardiac events. The HER2-enriched subtype isassociated with a high rate of pCR.

Idioma: Inglés

DOI: 10.1186/s12916-018-1233-1

Año: 2019

Publicado en: BMC Medicine 17, 1 (2019), 8 [12 pp]
ISSN: 1741-7015

Factor impacto JCR: 6.782 (2019)

Categ. JCR: MEDICINE, GENERAL & INTERNAL rank: 15 / 165 = 0.091 (2019) - Q1 - T1

Factor impacto SCIMAGO: 3.552 - Medicine (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI16-00904

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Area Medicina (Dpto. Medicina, Psiqu. y Derm.)