Results Announced for Phase III Head-to-head Study of Halaven®
(eribulin) Versus Capecitabine (Xeloda®) in Patients With Locally
Advanced or Metastatic Breast Cancer
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
aggregates.
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 indications.
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 loss
- 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, Slovakia,
the Netherlands, Belgium, Luxembourg, the Middle East and Russia.
For further information please visit our web site
http://www.eisai.com.
References
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 -923
3. HER2-positive breast cancer: What
is it? http://www.mayoclinic.com/health/breast-cancer/AN00495 (last
accessed November 2012)
4. Summary of Product Characteristics
Halaven (updated March 2011).
Available at:
http://www.medicines.org.uk/EMC/medicine/24382/SPC/Halaven+0.44+mg+ml+solution+for+injection/
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): iv15-iv18
Date of preparation: December 2012
Job code: Halaven-UK0065