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

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

  PR Newswire

  HATFIELD, England, June 2, 2014

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


   Significant survival benefit observed in women with HER2 negative breast

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

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

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

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

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

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
  *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


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.
.Last accessed May 2014

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

Contact: Media Enquiries: Eisai Europe Ltd, Cressida Robson / Charlotte
Andrews, +44(0)7908-314-155 / +44(0)7947-231-513, Cressida_Robson@eisai.net /
Charlotte_Andrews@eisai.net; Tonic Life Communications: Siobhan Reilly / April
Kenneally, +44(0)207-798-9999 / +44(0)207-798-9263, siobhan.reilly@toniclc.com
/ april.kenneally@toniclc.com
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