The German Federal Joint Committee (G-BA), the supreme decision-making body of the self-governing medical system in Germany, announced that it considers the use of Halaven(R) (eribulin) to have additional benefit versus comparative treatments, defined by the G-BA for women who have already had extensive prior treatment of metastatic or locally advanced breast cancer.
Today's assessment by the G-BA is based on the results of the EMBRACE study, previously published in The Lancet. This pivotal phase III study, demonstrates that eribulin is the first, single-agent chemotherapy to show a statistically significant overall survival benefit in women with heavily pre-treated advanced breast cancer (compared to treatment of physician choice). Eribulin has an expected and manageable safety profile which is in line with other single-agent chemotherapy treatments for advanced breast cancer in this setting.
"Eisai recognises the decision of the G-BA which demonstrates support for innovative medicines in the area of oncology, where there are few treatment choices. The development of breakthrough chemotherapies such as Halaven is vital to prolong the time women with advanced breast cancer can spend with their loved ones." Commented Frank Zeymer, Eisai's Oncology Business Unit Director, Region Central, based in Germany.
Eribulin is approved in Europe for the treatment of patients with locally advanced or metastatic breast cancer whose disease has progressed after at least two chemotherapeutic regimens for advanced disease. Prior therapy should have included an anthracycline and a taxane unless patients were not suitable for these treatments.
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, Switzerland, Japan, and Singapore. In Europe, Halaven has received pricing authorisation and been launched in Austria, Denmark, Finland, Germany, Iceland, Italy, Norway, Sweden, Switzerland, Slovenia, and the UK.
Global Phase III Clinical Study (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 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 (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 patients involved in the EMBRACE trial. Neutropenia 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%.
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. Summary of Product Characteristics Halaven (updated March 2011). Available at: http://www.medicines.org.uk/EMC/medicine/24382/SPC/Halaven+0.44+mg+ml+so...
4. 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