Halaven® (Eribulin) Provides Clinical Benefit Without an Adverse Effect on Quality of Life: Data Presented at ESMO

HATFIELD, England, September 26, 2014 /PRNewswire/ --

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

Additional Pooled Phase III Data Presented at ESMO Show Significantly Improved Overall Survival for Eribulin Compared to Standard Therapies in Locally Advanced or Metastatic Breast Cancer  

Data from three posters presented at this year's European Society for Medical Oncology (ESMO) 2014 Congress provide further evidence on the efficacy and quality of life (QOL) profile of Halaven^® (eribulin) in the treatment of patients with locally advanced or metastatic breast cancer (MBC).^[1],[2],[3]

The results of a pooled analysis of eribulin from two pivotal Phase III trials, EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Treatment of Physician's Choice (TPC) Versus Eribulin E7389) and Study 301, show that the drug improves significantly overall survival (OS) following at least one prior chemotherapy in women with locally advanced or MBC, compared with other standard therapies. This OS benefit is seen in women with human epidermal growth-factor receptor-2 (HER2) negative, hormone receptor (HR) positive, HR negative and triple negative breast cancer (TNBC). Treatment differences are not significant in women with HER2 positive MBC.^[1]

"Metastatic breast cancer can be a devastating condition that impacts significantly on both the quality and quantity of women's lives. For many women with metastatic breast cancer, quality of life becomes a critical factor when considering the treatment options available. Treatment choices that can extend life without impairing a patient's quality of life mean that women can enjoy the extra time with their loved ones," comments 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.

In Study 301, analyses assessed health-related quality of life (HRQOL) using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QOLQ-C3). In these post hoc analyses conducted to assess the impact of eribulin and capecitabine treatment, more than three quarters of women maintain or improve their global health status/QOL throughout the study, with no significant differences between groups. However, a significantly greater proportion of women who receive capecitabine vs eribulin show clinically meaningful worsening of nausea/vomiting and diarrhoea which suggests that eribulin has a more favourable gastro-intestinal adverse event profile than capecitabine.^[3]

Another poster investigates the effect of MBC treatment on quality of life utility values at tumour response and disease progression. Compared to baseline, tumour response is associated with quality of life improvement for eribulin and capecitabine. However, compared to baseline, disease progression is associated with a decreased QOL. The following toxicities are associated with statistically significant reductions in QOL vs no toxicity: vomiting, fatigue/asthenia and dyspnea (shortness of breath).^[2]

"Quality of life is an important consideration for women with metastatic breast cancer, who often live for several years with the symptoms of their disease and the side effects of multiple treatments. Overall, these first quality of life data show that eribulin has a broadly similar impact on quality of life to capecitabine, which is generally considered a well-tolerated chemotherapy. Importantly, eribulin leads to less nausea, vomiting and diarrhoea which are often major concerns for both women and their physicians," comments Professor Galina Velikova, Professor of Psychosocial and Medical Oncology, and Honorary Consultant in Medical Oncology at the University of Leeds and St James's Institute of Oncology.

A total of eight eribulin abstracts are being presented during the ESMO 2014 Congress.

First approved by the European Commission in 2011, eribulin received European Marketing Authorisation Approval (MAA) in June 2014 for the treatment of women with locally advanced or metastatic breast cancer 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.^[4] The MAA for eribulin 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)^[5] and Study 301.^[6]

"We are dedicated to exploring the full potential of eribulin in women with advanced breast cancer. These women need effective treatment options that allow them to spend quality time with their family and loved ones. The data presented at this key congress provide further evidence that eribulin goes some way to addressing these needs," says Gary Hendler, President & CEO Eisai EMEA and President, Eisai Oncology Global Business Unit.

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 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.

Eribulin is currently indicated for the treatment of women with locally advanced or metastatic breast cancer 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.^[4]

EORTC QLQ-C30^[7] 

The EORTC quality of life questionnaire (QLQ) is an integrated system for assessing the health-related quality of life of cancer patients participating in international clinical trials. Developed over more than a decade of collaborative research, it is a questionnaire for patient self-completion, composed of multi-item and single scales. These include five functional scales (physical, role, emotional, social and cognitive), three symptom scales (fatigue, nausea & vomiting and pain) and a global health status/QoL scale and six single items (dyspnoea, insomnia, appetite loss, constipation, diarrhoea and financial difficulties). High scores on the functional scales indicate a high level of functioning and high scores on the global health status indicate a high QoL; by contrast, high scores on the symptom scales/items indicate high levels of health problems.

Global Phase III Clinical Study 305 (EMBRACE)^[5]

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 (OS) 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 MBC 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 OS in heavily pre-treated women with MBC 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 OS 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^[6]

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/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 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 OS 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 effective 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 MBC (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.^[8],[9]Metastatic disease is an advanced stage of the disease that occurs when cancer spreads beyond the breast to other parts of the body.

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 various 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. Twelves C et al. Efficacy of eribulin in a second-line or later setting in patients (pts) with metastatic breast cancer (MBC): a pooled analysis. Presented at ESMO 2014. Abstract #393P

2. Hudgens S, et al. Impact of treatment with eribulin (ERI0 or capecitabine (CAP) for metastatic breast cancer (MBC) on EQ-5D utility derived from EORTC QLQ-C30. Presented at ESMO. Abstract #1046P

3. Velikova G et al. Health-related quality of life (HRQOL) and disease symptoms in patients (pts) with locally advanced or metastatic breast cancer (MBC) treated with eribulin (ERI) or capecitabine (CAP) in a post anthracycline and taxane setting. Presented at ESMO. Abstract #392P

4. SPC Halaven (updated June 2014). Available at: http://www.medicines.org.uk/emc/medicine/24382/SPC/Halaven+0.44+mg+ml+solution+for+injection/  Accessed: September 2014

5. Cortes J 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

6. Kaufman P 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

7. Montazeri A et al. Quality of life in patients with breast cancer before and after diagnosis: an eighteen months follow up study. BMC Cancer. 2008. 3:330

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

9. Cancer Research UK. Breast cancer incidence statistics. Available at: http://www.cancerresearchuk.org/cancer-info/cancerstats/types/breast/incidence/#world . Accessed: September 2014

Date of preparation: September 2014  
Job code: Halaven-UK0344