Halaven® (Eribulin) in Combination with Capecitabine Provides Clinical Benefit for Women with Metastatic Breast Cancer

HATFIELD, England, December 9, 2014 /PRNewswire/ --

PRESS RELEASE FOR EU MEDIA ONLY: NOT FOR SWISS/U.S. JOURNALISTS  

A Second Phase II Study Presented at San Antonio Breast Cancer Symposium (SABCS) Show Eribulin Plus Capecitabine as Adjuvant Treatment, in People with Early, HER2-Normal/HER2 Negative and ER positive Breast Cancer, as a potential treatment option 

Results of a Phase II, open-label, dose-confirmation study of eribulin in combination with capecitabine, suggests that this therapy is efficacious in women with metastatic breast cancer (overall response rate 42.9% and clinical benefit rate 57.1%), with a safety and tolerability profile consistent with previous data. In combination, eribulin and capecitabine had a median progression free survival of 7.1 months (95% CI: 4.4, 9.8).^[1]

Data from five posters presented during the 2014 San Antonio Breast Cancer Symposium (SABCS) provide further evidence on the efficacy, safety and quality of life profile of eribulin, in the treatment of patients with locally advanced or metastatic breast cancer (MBC) and data in early stage breast cancer.^{[1],[2],[3],[4],[5]}

A second Phase II, multicentre, open-label study, explores the feasibility of eribulin plus capecitabine as an adjuvant therapy in women with early-stage, estrogen receptor (ER) positive breast cancer.^[2]

"A major short-coming of most chemotherapy combinations in metastatic breast cancer has been that although more active, the side effects of combinations are often unacceptable. This Phase II study suggests that eribulin in combination with capecitabine could provide an additional treatment option for women with metastatic breast cancer that is both effective and well tolerated," 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.

Two additional studies highlight quality of life outcomes for women treated with eribulin first line in monotherapy and combination with trastuzumab, respectively. The first Phase II study assesses eribulin as a first line therapy for women with HER2 negative metastatic breast cancer and generates a stable or improvement in quality of life scales measured by the EORTC scale, QLQ-C30.^[3] The second Phase II study investigates eribulin in combination with trastuzumab and shows positive improvements in pain and in arm and breast symptoms which warrant further investigation.^[4]

Additional data pooled from the pivotal Phase III trial EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Treatment of Physician's Choice Versus Eribulin)^[6], Study 301^[7]and a single-arm Phase II study highlights that the benefit of eribulin was similar for women with invasive lobular carcinoma and invasive ductal carcinoma (overall survival; 13.4 vs 13.6 months; hazard ratio [HR] = 1.07; 95% CIs 0.72, 1.10).^[5]Invasive lobular carcinoma is the second most common form of breast cancer subtype and is associated with lower response rates to preoperative chemotherapy compared to invasive ductal carcinoma. Results from this study contrast with data from current chemotherapies.

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.^[8] 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)^[6] and Study 301.^[7]

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.^[8]

Global Phase III Study 305 (EMBRACE)^[6]

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 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 overall survival 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 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^[7]

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 1.25 g/m2, administered orally twice daily on day 1 to 14, every 21 days.

Study 301 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 ITT population, although the improvement was not statistically significant. Women treated with eribulin had a median overall survival 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 (independent review) 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 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), overall survival 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, overall survival 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 and 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.^[9],[10]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%).

EORTC QLQ-C30^[11] 

The EORTC quality of life questionnaire (QLQ) is an integrated system to assess the health-related quality of life of people with cancer who participate 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 function 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.

About Eisai EMEA in Oncology  

Headquartered in the United Kingdom, the Eisai EMEA regional operations are based at the European Knowledge Centre in Hatfield, Hertfordshire, where the Group's production, drug discovery, clinical research and marketing functions are integrated into a single site. This centre serves as a significant hub from which to expand into pharmaceuticals markets throughout Europe, the Middle East and Africa as well as in Russia and Oceania.

Eisai's 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. Twelves C et al. Efficacy and safety of eribulin in combination with capecitabine in patients with metastatic breast cancer: an open-label, phase 2 dose-confirmation study. Presented at SABCS 2014. Abstract #P3-13-04

2. Smith JW. et al. Eribulin mesylate plus capecitabine for adjuvant treatment in post-menopausal ER+ early-stage breast cancer: a phase 2, multicenter, open-label study using 2 different dosage regimens. Abstract #P3-09-09

3. Schwartzberg LS. et al. Quality of life in patients receiving first-line eribulin mesylate for HER2- locally recurrent or MBC. Presented at SABCS 2014. Abstract P5-17-02

4. Schwartzberg LS. et al. Quality of life results from a phase 2, multicenter, single-arm study of eribulin mesylate plus trastuzumab as first-line therapy for locally recurrent or metastatic HER2+ breast cancer. Presented at SABCS 2014. Abstract #P5-17-03

5. Cortes J et al Efficacy of eribulin in patients with invasive lobular carcinoma of the breast: data from a pooled analysis. Presented at SABCS 2014. Abstract #P3-13-06

6. 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

7. 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

8. 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: December 2014

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

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

11. 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

Date of preparation: December 2014  
Job code: Halaven-UK0371