Women in Spain Now Able to Benefit from Advanced Breast Cancer Treatment Halaven® (eribulin) After Only One Prior Chemotherapy

HATFIELD, England, September 1, 2015 /PRNewswire/ --

PRESS RELEASE FOR EU MEDIA ONLY: NOT FOR SWISS/AUSTRIAN/U.S. JOURNALISTS 

Halaven, a life-extending treatment, to be available earlier for women in Spain

From today, women with locally advanced or metastatic breast cancer (MBC) in Spain will have access to Halaven^® (eribulin) after only one prior chemotherapy in the advanced setting. Eribulin is currently indicated for the treatment of patients with locally advanced or metastatic breast cancer who have progressed after at least one chemotherapeutic regimen for advanced disease in Spain. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting, unless patients were not suitable for these treatments.^[1]

"Since eribulin is the only single-agent chemotherapy proven to prolong overall survival in women with metastatic breast cancer, it is great news that we are now able to offer this therapy after one prior chemotherapy in the metastatic setting. Of particular note is the survival benefit seen in women with HER2 negative cancers, as this represents around 80% of all women with breast cancer," commented Javier Cortes, Head of the Breast Cancer Programme, Vall d'Hebron Institute of Oncology and University Hospital, Barcelona, Spain.

Breast cancer is the most common female cancer in Spain.^[2] There were over 25,000 diagnosed cases of breast cancer in women in Spain in 2012 with over 6,000 deaths resulting from the disease.^[2]

The decision is based on clinical evidence from two global Phase III trials; EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Treatment of Physician's Choice Versus eribulin)^[3] and study 301.^[4] These studies involved more than 1,800 women.

EMBRACE showed eribulin can prolong median overall survival in women with MBC compared to women receiving an alternative treatment of physician's choice by 2.7 months (13.2 vs 10.5 HR 0.81 (95% CI 0.67, 0.96) nominal p=0.014). The most commonly reported adverse reactions in the eribulin study arm were fatigue (asthenia), a decrease in infection-fighting white blood cells (neutropenia), hair loss (alopecia), numbness and tingling in arms and legs (peripheral neuropathy), nausea and constipation.^[3] EMBRACE is the only one of 25 studies to demonstrate a significant extension in overall survival (as primary or secondary endpoint) in MBC in the last 40 years.^[5]

Study 301, a head-to-head trial of eribulin vs capecitabine, had a co-primary endpoint of overall survival and progression-free survival. The study demonstrated a trend favouring improved overall survival with eribulin compared to capecitabine in the intention-to-treat population, although the improvement was not statistically significant.^[4] Women treated with eribulin had a median overall survival of 15.9 months versus 14.5 months with capecitabine (HR 0.879; 95% CI: 0.770-1.003; p=0.056).^[4] For women with human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer, overall survival was 15.9 months for eribulin vs 13.5 months for capecitabine (HR 0.838; 95% CI: 0.715-0.983).^[4] The most common adverse events reported for eribulin and capecitabine (≥20% all grades) were neutropenia (54% vs 16%), hand-foot syndrome (<1% vs 45%) alopecia (35% vs 4%), leukopenia (31% vs 10%), diarrhoea (14 vs 29%) and nausea (22% vs 24%), respectively.^[4]

Eisai is dedicated to discovering, developing and producing innovative oncology therapies that can make a difference and impact the lives of patients and their families. This passion for people is part of Eisai's human health care (hhc) mission, which strives for better understanding of the needs of patients and their families to increase the benefits health care provides.

Notes to Editors  

Halaven^® (eribulin)  

Eribulin is the first in the halichondrin class of microtubule dynamics inhibitors with a novel mechanism of action. Structurally eribulin is a simplified and synthetically produced version of halichondrin B, a natural product isolated from the marine sponge Halichondria okadai. Eribulin is believed to work by inhibiting the growth phase of microtubule dynamics which prevents cell division.

Global Phase III Clinical Study 305 (EMBRACE)^[3]

EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Treatment of Physician's Choice (TPC) versus eribulin E7389) was an open-label, randomised, global, multi-centre, parallel two-arm study designed to compare overall survival in women treated with eribulin versus a TPC arm. TPC was defined as any single-agent chemotherapy, hormonal treatment or biologic therapy approved for the treatment of cancer; or palliative treatment or radiotherapy administered according to local practice. The study included 762 participants with metastatic breast cancer who previously had been treated with at least two and a maximum of five prior chemotherapies, including an anthracycline and a taxane. The vast majority (96%) of participants in the TPC arm received chemotherapy.

In the total phase III EMBRACE study population, eribulin was shown to prolong median overall survival in heavily pre-treated women with metastatic breast cancer compared to women receiving TPC by 2.7 months (13.2 vs 10.5 HR 0.81 (95% CI 0.67, 0.96) nominal p=0.014). A pre-planned analysis of participants from Region 1 of the study (North America/Western Europe/Australia) showed a significant median overall survival benefit of eribulin over TPC of 3.0 months (nominal p=0.031).

The most commonly reported adverse reactions among people treated with eribulin in the EMBRACE study were fatigue (asthenia), a decrease in infection-fighting white blood cells (neutropenia), hair loss (alopecia), numbness and tingling in arms and legs (peripheral neuropathy), nausea and constipation. Peripheral neuropathy was the most common adverse event leading to discontinuation from eribulin, occurring in less than 5% of the women involved in the EMBRACE trial. Neutropenia only led to eribulin discontinuation for 0.6%. Death due to serious side effects, discontinuation and dose interruptions to treatment were lower in the eribulin arm of the trial compared with the TPC arm.

Global Phase III Study 301^[4]

Study 301 was an open-labelled, randomised, two-parallel-arm, multicentre study of eribulin versus capecitabine in 1,102 women with locally advanced or metastatic breast cancer previously treated with anthracyclines and taxanes, either in the (neo) adjuvant setting or for locally advanced or metastatic disease. Women in the study received zero to two previous chemotherapies for advanced disease.

The study opened in 2006 and the last patient was randomised in 2010. Patients were randomised to treatment with either eribulin 1.23mg/m² (administered intravenously over two to five minutes on days 1 and 8, every 21 days) or capecitabine 2.5g/m² (administered orally twice daily in two equal doses on days 1 to 14, every 21 days).

Study 301 had a co-primary endpoint of OS and PFS. The study demonstrated a trend favouring improved OS with eribulin compared to capecitabine in the ITT population, although the improvement was not statistically significant. Women treated with eribulin had a median OS of 15.9 months (HR 0.879; 95% CI: 0.770-1.003; p=0.056) versus 14.5 months with capecitabine. The trial did not meet the pre-specified endpoint for progression-free survival, with 4.1 and 4.2 months for Eribulin and capecitabine respectively (HR 1.079; 95% CI: 0.932-1.250; p=0.305).

1-, 2- and 3- year overall survival rates for eribulin versus capecitabine showed an early improvement which was maintained throughout the study (1 year, 64.4% eribulin vs 58.0% capecitabine (P=0.0351), 2 year 32.8% eribulin vs 29.8% capecitabine (P=0.324), 3 year, 17.8% eribulin vs 14.5% capecitabine (P=0.175).

Unlike studies conducted today, study 301 included all women regardless of their human epidermal growth factor receptor 2 (HER2), oestrogen receptor (ER) or progesterone receptor (PR) status. Patients are usually tested for their HER2 status as there are now treatments specifically for patients with the HER2 mutation.  HER2 positive patients would generally be treated with anti-HER2 positive targeted therapy. For women with HER2 negative metastatic breast cancer (n=755), OS was 15.9 months for eribulin vs 13.5 months for capecitabine (HR 0.838; 95% CI: 0.715-0.983). In the HER2 positive population, OS was 14.3 months for eribulin vs 17.1 months for capecitabine (HR; 95% 0.965; CI: 0.688-1.355).

Adverse events in Study 301 were consistent with the known profile of both drugs.

Metastatic Breast Cancer  

Over 300,000 women are diagnosed with breast cancer in Europe every year, of whom about one third subsequently develop metastatic disease.^[6],[7] Metastatic disease is an advanced stage of the disease that occurs when cancer spreads beyond the breast to other parts of the body.

HER2 is a protein that is found on the surface of cells. In HER2-positive breast cancer there is more (over expression) of this protein found on the surface of tumour cells compared with normal breast cells. This protein can be targeted with HER2 targeted therapies such as Herceptin, in people who overexpress HER2, but not in people with normal levels of HER2 protein (HER2-negative) breast cancer. Breast cancers are routinely tested for the presence of HER2 to decide the most appropriate treatment. Triple-negative breast cancer (TNBC) refers to any breast cancer that does not express the genes for oestrogen receptor, progesterone receptor (<1%) and HER2 (<30%).

Eisai in Oncology  

Our commitment to meaningful progress in oncology research, built on scientific expertise, is supported by a global capability to conduct discovery and preclinical research, and develop small molecules, therapeutic vaccines, and biologic and supportive care agents for cancer across multiple indications.

About Eisai Co., Ltd. 

Eisai Co., Ltd. is a leading global research and development-based pharmaceutical company headquartered in Japan. We define our corporate mission as "giving first thought to patients and their families and to increasing the benefits health care provides," which we call our human health care (hhc) philosophy. With over 10,000 employees working across our global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to realise our hhc philosophy by delivering innovative products in multiple therapeutic areas with high unmet medical needs, including Oncology and Neurology. 

As a global pharmaceutical company, our mission extends to patients around the world through our investment and participation in partnership-based initiatives to improve access to medicines in developing and emerging countries.

For more information about Eisai Co., Ltd., please visit http://www.eisai.com.  

References  

1. European Commission Implementing Decision for Halaven received June 2014

2. EUCAN Factsheet Spain. Available at: http://eco.iarc.fr/eucan/Country.aspx?ISOCountryCd=724 . Last accessed August 2015

3. Cortes J, O'Shaughnessy J, Loesch D, et al. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. The Lancet. 2011;377:914-923

4. Kaufman P, Awada A, Twelves C et al. A Phase III, open-label, randomised, multicenter study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with anthracyclines and taxanes. Presented at 2012 CTRC-AACR San Antonio Breast Cancer Symposium

5. Data on File. ERI-099 Improvement in Overall Survival in Metastatic Breast Cancer

6. World Health Organisation. Atlas of Health in Europe. 2003. World Health Organization, Regional Office of Europe, Copenhagen, Denmark.

7. Cancer Research UK. Breast cancer incidence statistics. Available at: http://www.cancerresearchuk.org/cancer-info/cancerstats/types/breast/incidence/ #world. Last accessed: August 2015

Date of preparation: August 2015
Job code: Halaven-UK0430