Pooled Analysis of Two Phase III Trials Shows Halaven® (Eribulin) Improves Survival in Advanced Breast Cancer

HATFIELD, England, June 2, 2014 /PRNewswire/ --

FOR EMEA MEDIA ONLY: NOT FOR SWISS/U.S. JOURNALISTS 

Significant survival benefit observed in women with HER2 negative breast cancer 

Data from a pooled analysis presented today at the 50^th Annual Meeting of the American Society of Clinical Oncology (ASCO) provides further evidence that Halaven^® (eribulin) improves overall survival (OS) in women with advanced breast cancer compared with other standard therapies (15.2 vs 12.8 months, HR=0.85 [95% CI, 0.77-0.95]; p=0.003).^[1] In particular, a significant OS benefit was observed in women with human epidermal growth-factor receptor-2 (HER2) negative breast cancer (15.2 vs 12.3 months, HR=0.82 [95% CI, 0.72-0.93]; p=0.002), a subtype that affects an estimated 85% of women with breast cancer.^[1]

This OS benefit was also seen in people with triple negative breast cancer (TNBC),(12.9 vs 8.2 months, HR=0.74 [95% CI, 0.60-0.92]; p=0.006), but not in women with HER2 positive breast cancer (13.5 vs 12.2 months, HR=0.82 [95% CI, 0.62-1.06]; p=0.135). There were no noticeable differences in the tolerability and safety data previously shown in the EMBRACE and 301 studies.^[1]

"Eribulin remains the only single agent chemotherapy proven to improve significantly overall survival in women with advanced breast cancer after either adjuvant or metastatic anthracycline and taxane treatment. These new data clearly confirm that women with advanced breast cancer benefit from eribulin. The overall survival benefit that was observed in HER2 negative and triple negative breast cancer patients is particularly interesting as very often these patients are underserved with few effective treatment options," commented Dr Chris Twelves, Professor of Clinical Cancer Pharmacology and Oncology and Honorary Consultant in Medical Oncology at the University of Leeds and St James's Institute of Oncology.

The pooled analysis examined data from two pivotal Phase III studies of more than 1,800 women; EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Treatment of Physician's Choice Versus Eribulin)^[2] and study 301.^[3] The objective of the analysis, requested by the European Medicines Agency (EMA), was to assess OS in the overall intent to treat (ITT) population and in subgroups based on HER2 and hormone receptor status.

A total of 12 abstracts have been accepted at this year's ASCO congress highlighting the ongoing clinical development of eribulin in women with difficult to treat metastatic breast cancer sub-types, in combination with other agents and in different therapeutic areas.

On 27 May 2014, the EMA's Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion for eribulin for the treatment of patients with locally advanced or metastatic breast cancer (MBC) 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.

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.

Since the launch of eribulin in the U.S. in 2010, 49,000 women have been treated with eribulin globally.^[4]

305/301 Pooled Data^[1]

The pooled analysis included data from EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Treatment of Physician's Choice (TPC) Versus Eribulin) and involved women who received 2-5 lines of chemotherapy for advanced disease. In this third line setting, women were randomised 2:1 to receive eribulin (1.23 mg/m^[2] iv on days 1 and 8 every 21 days) or TPC. The second study in the pooled analysis (study 301) included women who had received 0-2 prior chemotherapies for advanced disease who were randomised 1:1 to receive either eribulin (dose schedule as per EMBRACE) or capecitabine (1.25 g/m^[2] orally twice daily on days 1-14 every 21 days). The objective of this pooled analysis was to assess overall survival in the overall ITT population and in subgroups based on HER2 and hormone-receptor status.

Global Phase III Clinical Study 305 (EMBRACE)^[2]

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 people treated with eribulin versus a Treatment of Physician's Choice (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 people 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 people in the TPC arm received chemotherapy.

In the total Phase III EMBRACE study population, eribulin was shown to prolong median overall survival in people heavily pre-treated metastatic breast cancer compared to people 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 people 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 people involved in the EMBRACE study. Death due to serious side effects, discontinuation and serious adverse events were lower in the eribulin arm of the study compared with the TPC arm.

Global Phase III Study 301^[3]

Study 301 was an open-labelled, randomised, two-parallel-arm, multicentre study of Halaven (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. This study was outside of the licensed indication for eribulin. Participants 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 overall survival (OS) and progression-free survival (PFS). The study demonstrated a trend favouring improved OS with eribulin compared to capecitabine in the intention-to-treat (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]

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=0.035), 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 not be treated with non-HER2 positive directed therapy. In an exploratory analysis for the planned subset of HER2 negative women (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 (HR0.965; 95% CI: 0.688-1.355).

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

Metastatic Breast Cancerand the HER2 Protein 

Over 300,000 women are diagnosed with breast cancer in Europe every year, of whom about one third subsequently develop metastatic disease.^[5],[6]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 and HER2.

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 

Eisai is one of the world's leading research and development (R&D) based pharmaceutical companies and 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 human health care (hhc).

Eisai concentrates its R&D activities in three key areas:

• Oncology including: anticancer therapies; tumour regression, tumour suppression, antibodies, etc.
• Neuroscience, including: Alzheimer's disease, epilepsy, pain and weight loss
• Vascular/Immunological reaction including: thrombocytopenia, rheumatoid arthritis, psoriasis, inflammatory bowel disease

With operations in the U.S., Asia, Europe and its domestic home market of Japan, Eisai employs more than 10,000 people worldwide. From its EMEA Knowledge Centre in Hatfield, UK, Eisai has recently expanded its business operations to include Europe, the Middle East, Africa, Russia and Oceania (EMEA). Eisai EMEA has sales and marketing operations in over 20 markets, including the United Kingdom, France, Germany, Italy, Spain, Switzerland, Sweden, Ireland, Austria, Denmark, Finland, Norway, Portugal, Czech Republic, Slovakia, the Netherlands, Belgium, Luxembourg, Russia and the Middle East.

For further information please visit our web site http://www.eisai.co.uk

References  

1. Twelves C, Cortes J et al.  Efficacy of eribulin in patients with metastatic breast cancer: a pooled analysis by HER2 and ER status. Presented at ASCO 2014.Poster #: 95

2. 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

3. 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

4. Eisai data on file. May 2014

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

6. Cancer Research UK. Breast cancer incidence statistics. http://www.cancerresearchuk.org/cancer-info/cancerstats/types/breast/incidence/#world. Last accessed May 2014

Date of preparation: June 2014  
Job code: Halaven-UK0287