Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study : The Lancet

The Lancet, Early Online Publication, 3 March 2011doi:10.1016/S0140-6736(11)60070-6Cite or Link Using DOIEribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study

Original Text
Javier Cortes MD a, Joyce O'Shaughnessy MD b, David Loesch MD c, Joanne L Blum MD b, Linda T Vahdat MD d, Katarina Petrakova MD e, Philippe Chollet MD f, Alexey Manikas MD g, Veronique Diéras MD h, Thierry Delozier MD i, Vladimir Vladimirov MD j, Fatima Cardoso MD k, Han Koh MD l, Philippe Bougnoux MD m, Corina E Dutcus MD n, Seth Seegobin MSc o, Denis Mir MSc o, Nicole Meneses MSHS n, Jantien Wanders MD o, Prof Chris Twelves MD p , on behalf of the EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician's Choice Versus E7389) investigators

Summary

Background
Treatments with survival benefit are greatly needed for women with heavily pretreated metastatic breast cancer. Eribulin mesilate is a non-taxane microtubule dynamics inhibitor with a novel mode of action. We aimed to compare overall survival of heavily pretreated patients receiving eribulin versus currently available treatments.

Methods
In this phase 3 open-label study, women with locally recurrent or metastatic breast cancer were randomly allocated (2:1) to eribulin mesilate (1·4 mg/m2 administered intravenously during 2—5 min on days 1 and 8 of a 21-day cycle) or treatment of physician's choice (TPC). Patients had received between two and five previous chemotherapy regimens (two or more for advanced disease), including an anthracycline and a taxane, unless contraindicated. Randomisation was stratified by geographical region, previous capecitabine treatment, and human epidermal growth factor receptor 2 status. Patients and investigators were not masked to treatment allocation. The primary endpoint was overall survival in the intention-to-treat population. This study is registered at ClinicalTrials.gov, number NCT00388726.

Findings
762 women were randomly allocated to treatment groups (508 eribulin, 254 TPC). Overall survival was significantly improved in women assigned to eribulin (median 13·1 months, 95% CI 11·8—14·3) compared with TPC (10·6 months, 9·3—12·5; hazard ratio 0·81, 95% CI 0·66—0·99; p=0·041). The most common adverse events in both groups were asthenia or fatigue (270 [54%] of 503 patients on eribulin and 98 [40%] of 247 patients on TPC at all grades) and neutropenia (260 [52%] patients receiving eribulin and 73 [30%] of those on TPC at all grades). Peripheral neuropathy was the most common adverse event leading to discontinuation from eribulin, occurring in 24 (5%) of 503 patients.

Interpretation
Eribulin showed a significant and clinically meaningful improvement in overall survival compared with TPC in women with heavily pretreated metastatic breast cancer. This finding challenges the notion that improved overall survival is an unrealistic expectation during evaluation of new anticancer therapies in the refractory setting.

Funding
Eisai.
Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study : The Lancet





ONCOLOGÍA
Un nuevo tratamiento mejora la supervivencia de pacientes con cáncer de mama metastásico
JANO.es · 03 Marzo 2011 11:05

.Se trata de la eribulina, según muestran los resultados de un estudio que ha liderado el Dr. Javier Cortés, responsable del Programa de Cáncer de Mama del Hospital Vall d’Hebron de Barcelona.


Un ensayo clínico liderado por el Dr. Javier Cortés, responsable del Programa de Cáncer de Mama del Hospital Vall d’Hebron y del Instituto de Investigación Vall d’Hebron (VHIO), ha demostrado que la eribulina, agente quimioterápico obtenido a partir de una esponja marina de origen animal, mejora el pronóstico de las pacientes afectadas de cáncer de mama metastásico. El estudio, denominado EMBRACE, se publica en The Lancet y su finalidad ha sido demostrar la eficacia del tratamiento.

Concretamente, demuestra que la administración de eribulina es una alternativa terapéutica más eficaz que los tratamientos actuales para pacientes
pretratadas con cáncer de mama metastásico que ya han recibido tratamiento con antraciclinas y taxanos.

La eribulina es un antimicrotúbulo que bloquea la división celular y forma compuestos tóxicos para la célula tumoral. En estos momentos, el tratamiento tiene prevista su aplicación, una vez aprobado por las administraciones competentes, en pacientes con cáncer de mama avanzado que ya hayan sido tratadas previamente.

Según los resultados del estudio, la supervivencia de las pacientes tratadas con este fármaco ha aumentado de media un 20%, con resultados de baja toxicidad y buena tolerancia.

El estudio clínico se ha realizado conjuntamente con centros de Estados Unidos, Checoslovaquia, Francia, Rusia, Bélgica, España e Inglaterra, entre otros. En Noviembre de 2010 la FDA americana aprobó su comercialización en Estados Unidos y se espera que la Agencia Europea del Medicamento la apruebe este año (2011).



The Lancet 2011;doi:10.1016/S0140-6736(11)60070-6
Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study : The Lancet

Actualidad Ultimas noticias - JANOes - Un nuevo tratamiento mejora la supervivencia de pacientes con cancer de mama metastasico - JANO.es - ELSEVIER