Results Announced for Phase III Head-to-head Study of Halaven® (eribulin) Versus Capecitabine (Xeloda®) in Patients With

  Results Announced for Phase III Head-to-head Study of Halaven® (eribulin)
Versus Capecitabine (Xeloda®) in Patients With Locally Advanced or Metastatic
                                Breast Cancer

  PR Newswire

  HATFIELD, UK, December 7, 2012

HATFIELD, UK, December 7, 2012 /PRNewswire/ --

For EU Medical Media Only

  Second large Phase III study for eribulin presented at San Antonio Breast
                               Cancer Symposium

Results from a global Phase III study (Study 301) of Halaven ^® (eribulin) in
women with metastatic breast cancer (MBC) were presented today during a
plenary session at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium. For
the first time this study compares eribulin and capecitabine (Xeloda ^® ) in
women with earlier stage locally advanced or MBC. This study, one of the
largest evaluating monotherapy chemotherapy, confirms eribulin as an active
drug in patients with MBC, and exploratory analyses suggest possible benefits
of eribulin in specific subset of patients, sufficient to warrant further
studies. ^[1]

Eribulin is currently approved for use in later line patient populations,
where the pivotal Phase III trial (EMBRACE) demonstrated a statistically
significant overall survival (OS) versus current single agent treatments and
showed eribulin had a predictable and manageable safety profile. ^[2]

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=0.0351), 2 year 32.8% eribulin vs
29.8% capecitabine (P=0.3235), 3 year, 17.8% eribulin vs 14.5% capecitabine
(P=0.1751). ^[ ^1 ^]

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. ^[3] 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;
nominal p=0.030). 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).

Professor Christopher Twelves, Professor of Clinical Cancer Pharmacology and
Oncology, University of Leeds and St James' University Hospital and Co-Primary
Investigator for the trial commented, "It is important to note that eribulin
is the first and only single-agent chemotherapy being assessed against
capecitabine in this setting. The results suggest that there is a possible
clinical advantage over capecitabine in certain patient populations that
warrants further analysis to fully understand the implications of this study
in clinical practice."

"Eisai remains committed to evaluating the safety and efficacy of eribulin in
women living with locally advanced or MBC and are using these results to
consider further evaluations," said Kenichi Nomoto, Ph.D., President, Oncology
Product Creation Unit at Eisai.

Furthermore, adverse events in Study 301 were consistent with the known
profile of both drugs. The most common AEs for eribulin and capecitabine (≥20%
all grades) were neutropaenia (54.2% vs 15.9%), hand-foot syndrome (0.2% vs
45.1%) alopecia (34.6% vs 4.0%), leukopaenia (31.4% vs 10.4%), diarrhoea (14.3
vs 28.8%) and nausea (22.2% vs 24.4%), respectively. ^[ ^1 ^]

Eribulin is the first and only single-agent therapy proven to significantly
extend overall survival after two prior lines of MBC therapy when compared to
other single-agent therapies. Results from a pivotal Phase III study (EMBRACE)
demonstrated a statistically significant overall survival benefit for women
treated with eribulin compared with a single-agent treatment of physician's
choice (TPC). Women entering the EMBRACE trial had more advanced disease than
those entering Study 301. [2]

Eribulin is currently indicated in Europe for the treatment of women with
locally advanced or MBC who have previously received at least two
chemotherapeutic regimens. Prior therapy should have included an anthracycline
and a taxane unless women were not suitable for these treatments. ^[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 indicated for the
treatment of patients 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. ^[ ^4 ^] 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 without
affecting the shortening phase and sequesters tubulin into non-productive

Halaven is approved in the European Union, USA, Russia, Switzerland, South
Korea, Japan, and Singapore. Halaven has received pricing authorisation and
has launched in Canada, Denmark, Finland, France, Iceland, Italy, Norway,
Sweden, Switzerland, Slovenia, and the UK. In addition, Halaven is available
in Austria and Germany.

Global Phase III Study 301 ^[ ^1 ^]

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. Patients 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).

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 patients 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 patients 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 patients
in the TPC arm received chemotherapy.

In the total Phase III EMBRACE study population, eribulin was shown to prolong
overall survival in heavily pre-treated patients with metastatic breast cancer
compared to patients receiving TPC by 2.7 months (13.2 vs 10.5 HR 0.81 (95% CI
0.067, 0.96) nominal p=0.014). A pre-planned analysis of patients from Region
1 of the study (North America/Western Europe/Australia) showed a significant
overall survival benefit of eribulin over TPC of 3.0 months (nominal p=0.031).

The most commonly reported adverse reactions among patients treated with
eribulin in the EMBRACE study were fatigue (asthenia), a decrease in
infection-fighting white blood cells (neutropaenia), 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 patients
involved in the EMBRACE trial. Neutropaenia only led to eribulin
discontinuation for 0.6% patients. 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.

Metastatic Breast Cancer

Metastatic breast cancer is an advanced stage of the disease that occurs when
cancer spreads beyond the breast to other parts of the body. In Europe,
approximately 6% of breast cancers are metastatic at diagnosis with a
five-year survival rate of 21%. ^[5]

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 recently expanded their UK Hatfield commercial, research and
manufacturing facility which now supports the company's growing EMEA business.

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

  *Neuroscience, including: Alzheimer's disease, epilepsy, pain and weight
  *Oncology including: anticancer therapies; tumour regression, tumour
    suppression, antibodies, etc.
  *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 11,000 people worldwide. In Europe, Eisai
undertakes sales and marketing operations in over 20 markets, including the
United Kingdom, France, Germany, Italy, Spain, Switzerland, Sweden, Ireland,
Austria, Denmark, Finland, Norway, Portugal, Iceland, Czech Republic,
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For further information please visit our web site .


1. 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

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

3. HER2-positive breast cancer: What is it? (last accessed November

4. Summary of Product Characteristics Halaven (updated March 2011). Available

5. Cardoso, M. and Castiglione F. Locally recurrent or metastatic breast
cancer: ESMO Clinical Recommendations for diagnosis, treatment and follow-up.
On behalf of the ESMO Guidelines Working Group. Ann Oncol (2009) 20 (suppl 4):

Date of preparation: December 2012

Job code: Halaven-UK0065

Contact: Media Enquiries: Eisai Europe Ltd, Charlotte Andrews / Cressida
Robson, +44(0)7947-231513, +44(0)790-831-4155, /; Tonic Life Communications, Siobhan Reilly / April
Kenneally, +44(0)207-798-9999 / +44(0)784-047-3199, +44(0)207-798-9263 /
+44(0)788-561-4274, /
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