HATFIELD, England, June 3, 2013 /PRNewswire/ --
NOT FOR U.S. MEDIA
New data presented at the ASCO 2013 congress today showed that over the course of a Phase III study (Study 301), Halaven® (eribulin) improved Global Health Status (GHS) and overall quality of life (QoL) more than capecitabine in patients with locally advanced or metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes.
Cancer and its treatment have a major impact on patient QoL such as difficulty fulfilling family roles, the ability to work, or participating in common social activities. For MBC patients, extending life for as long as possible whilst achieving the best QoL possible is central to the goal of treatment. Effectivedisease management allows treatment to be continued until a patient's cancer progresses and ensures the maximum benefits of treatment are achieved.
Study 301 did not meet the co-primary endpoints for overall survival or progression-free survival. However, the data showed a trend toward improved overall survival in patients treated with Halaven with a median survival of 15.9 months versus 14.5 months with capecitabine (HR 0.879; 95% CI 0.770, 1.003; p=0.056).
The Phase III study explored, as a secondary endpoint, the QoL-related experiences of 1,102 women receiving the study drugs, eribulin or capecitabine, as first, second or third line therapy. Their experiences were recorded on a series of scales relating to their symptoms, functioning, and overall well-being.
"The perceived quality of life associated with a treatment is a critical factor for women with advanced breast cancer in beginning or continuing with that treatment," said study investigator Dr Javier Cortes from the Vall d'Hebron University Hospital, Barcelona, Spain. "At an advanced stage of the disease, these women consider more than ever the impact of treatment on their ability to spend time with family, or live life as fully as possible. These new data show that overall quality of life is better over the course of treatment with eribulin compared with capecitabine."
GHS/QoL scores were low at the start of the study for both drugs however results showed GHS/QoL and cognitive functioning had improved significantly more in patients receiving eribulin compared to capecitabine over the course of the study (15.3 [p0.001] and 6.5 [p=0.048] respectively). Emotional functioning was found to improve to a greater extent in the capecitabine patients (3.3 [p=0.033]). Patients receiving eribulin reported significantly fewer symptoms associated with nausea and vomiting (1.9 [p=0.043]) and diarrhoea (-3.7 [p=0.001]), whereas patients receiving capecitabine reported fewer systemic side effects (5.2 [p0.001]) and were less upset by hair loss (9.3 [p=0.023]).
Collecting and reporting QoL data offer women with MBC a better understanding of how they may be affected by an individual treatment, empowering them to make informed choices as well as help them deal with their disease and its treatment.
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 of 2.7 months for women treated with eribulin compared with a single-agent treatment of physician's choice (TPC) (13.2 vs 10.5 HR 0.81 (95% CI 0.067, 0.96) nominal p=0.014).
Eribulin is indicated in Europe for the treatment of patients 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 patients were not suitable for these treatments.
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
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. 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 been 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
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. This study was outside of the licensed indication for eribulin. Patients in the study received zero to two previous chemotherapies for advanced disease.
Patients were randomised from 2006-2010, to treatment with either eribulin 1.4mg/m2 (administered intravenously over two to five minutes on days 1 and 8, every 21 days) or capecitabine 1.25g/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 overall survival (OS) and progression-free survival (PFS). The study demonstrated a trend favouring improved OS with eribulin compared to capecitabine, 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). Adverse events in Study 301 were consistent with the known profile of both drugs.
Study 301 had a secondary endpoint of QoL assessed using the EORTC QLQ-C30 and QLQ-BR23 questionnaires at baseline, 6 weeks, 3, 6, 12, 18 and 24 months after starting treatment or until progressive disease or treatment change, and at unscheduled visits. Longitudinal analyses were carried out using weighted generalised estimating equations adjusted for non-random attrition due to death within 12 months. Model covariates were time (visit), region, and baseline QoL. The primary endpoint for QOL was change from baseline for Global Health Status (GHS)/overall QoL, and exploratory endpoints were change from baseline for a range of functions and signs/symptoms.
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.
The QLQ-BR23 is a specific questionnaire containing 23 items measuring functioning and symptoms related to breast cancer, such as the common side effects of therapy, body image, sexuality, and outlook for the future. QLQ BR23 should be administered in addition to the core questionnaire (EORTC QLQ-C30) and, like the core questionnaire, is designed for use in cancer clinical trials.
Global Phase III Clinical Study 305 (EMBRACE)
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 median 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 median 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
Over 300,000 women are diagnosed with breast cancer in Europe every year, of whom about one third subsequently develop metastatic disease.,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
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1. Cortes J et al. Quality of Life in patients with locally advanced or metastatic breast cancer previously treated with anthracyclines and taxanes who received eribulin mesylate or capecitabine: a Phase II, open label, randomised study. ASCO 2013 abstract 1050^
2. European Organisation for Research and Treatment of Cancer (EORTC) http://groups.eortc.be/qol/quality-life (last accessed April 2013)
3. Breast Cancer Org. Living with Metastatic Disease: http://www.breastcancer.org/symptoms/types/recur_metast/living_metast (Last accessed April 2013)
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. Abstract No. S6-6
5. 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
6. 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
7. World Health Organization. Atlas of Health in Europe. 2003. World Health Organization, Regional Office of Europe, Copenhagen, Denmark.
8. Cancer Research UK. Breast cancer incidence statistics. http://www.cancerresearchuk.org/cancer-info/cancerstats/types/breast/incidence/#world [http://www.cancerresearchuk.org/cancer-info/cancerstats/types/breast/incidence ] (last accessed April 2013)
Date of preparation: May 2013
Job code: Halaven-UK0142
SOURCE Eisai Europe Limited