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

Hatfield, England (ots/PRNewswire) -

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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(R) (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 (greater than or equal to20% 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(R) (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

ots Originaltext: Eisai
Im Internet recherchierbar: http://www.presseportal.de

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