Halaven® (Eribulin) Now Available in Russia for Advanced Breast Cancer After Only One Prior Chemotherapy, Which Provides New Therapy for Women Living With Aggressive Disease

HATFIELD, England, December 18, 2014 /PRNewswire/ --

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

Eisai is pleased to announce that women with locally advanced or metastatic breast cancer (MBC) in Russia will have earlier access to Halaven^® (eribulin). Eribulin is now indicated for patients with locally advanced or metastatic breast cancer who have progressed after at least one chemotherapeutic regimen for advanced disease. 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]

"The new licence for eribulin in Russia will give physicians and women with advanced breast cancer more options in earlier treatment. Eribulin remains the only single-agent chemotherapy proven to prolong overall survival in women with pre-treated metastatic breast cancer," commented Professor Vera Gorbunova, MD, head of the chemical therapy department at the Russian Blokhin Oncologic Research Centre.

In Russia, breast cancer is the most common cause of death in women aged 45-55 years, and that has increased by 64% over the last 20 years alone. Furthermore, approximately 50,000 Russian women are newly diagnosed with breast cancer each year with around one in every eight women at risk of developing the disease.^[2]

"Eisai is pleased that the Russian health authorities have recognised the benefit of earlier use of eribulin therapy in women with HER2-negative metastatic breast cancer. More must be done for these women who actually make up the majority of advanced disease cases. We are committed to championing the needs of these women and broadening access to eribulin to help redress the inequality between HER2-negative and HER2-positive breast cancer outcomes in Russia and across Europe," said Gary Hendler, President & CEO Eisai EMEA.

The new indication for eribulin follows Marketing Authorisation Approval (MAA) for earlier use in advanced disease from the European Commission on 3 July 2014. 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 heavily pre-treated 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 are 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 one of only 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 (HER 2) negative metastatic breast cancer, overall survival was 15.9 months vs 13.5 months for capecitabine (HR 0.838; 95% Cl: 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 women 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 a non-taxane, microtubule dynamics inhibitor currently indicated for the treatment of people with breast cancer who have previously received at least two chemotherapeutic regimens for metastatic disease and whose prior therapy should have included an anthracycline and a taxane.Eribulin belongs to a class of antineoplastic agents, the halichondrins, which are natural products, isolated from the marine sponge Halichondria okadai. It 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/m^[2] (administered intravenously over two to five minutes on days 1 and 8, every 21 days) or capecitabine 2.5g/m^[2] (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 effective 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 (n=169), 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  

Metastatic disease is an advanced stage of the disease that occurs when cancer spreads beyond the breast to other parts of the body.

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. Women's Health Empowerment Program Moscow and Central Russia. www.hsph.harvard.edu/breastandhealth/files/ekaterina_bashta.pdf . Last accessed December 2014

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

Date of preparation: December 2014

Job code: Halaven-UK0380