HATFIELD, England, November 3, 2014 /PRNewswire/ --
Reassessment acknowledges survival benefit for eribulin in difficult-to-treat HER2-negative breast cancer also in the expanded indication
The German Institute for Quality and Efficiency in Health Care (IQWiG) has today published a report which concludes that an additional benefit of Halaven® (eribulin) versus certain comparator therapies as defined by the Federal Joint Committee (G-BA) for the treatment of women with locally advanced or metastatic breast cancer who have progressed after at least one chemotherapeutic regimen for advanced disease has been proven.[1] 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.[2] IQWiG has limited this positive assessment to patients who can no longer be treated with taxanes or anthracyclines. In the report published by the IQWiG, the Institute subsequently defined sub-populations and assessed the extent and probability of an additional benefit. Eisai is critical of some aspects of this approach and will address them in its written statement to the GB-A.
The G-BA is expected to publish its final decision after due consideration of the IQWiG report, written statements and an oral hearing at the end of January 2015.
The reassessment for eribulin is based on clinical evidence derived from two global Phase III trials; EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Treatment of Physician's Choice Versus E7389)[3] (Study 305) and Study 301.[4]These studies involved more than 1,800 women. In line with the G-BA requirements, additional pooled analyses of data have been specifically performed for the benefit assessment procedure in Germany and reviewed by IQWiG.
"Eribulin is an important and effective treatment option that can and should be given to women earlier in their treatment pathway following this year's indication extension. Eribulin remains the only single-agent chemotherapy proven to extend overall survival in metastatic breast cancer after anthracycline and taxane treatment, and this partially positive assessment by IQWiG will be welcomed by physicians and patients across the country. We look forward to the G-BA's decision and expect it will confirm the experience made in real-world treatment over the last few years and support the earlier use of eribulin." said Dr Christian Jackisch Professor of Obstetrics and Gynaecology at the Breast Cancer Center Klinikum Offenbach, Germany.
Breast cancer is the most common and most fatal female cancer in Germany.[5] There were over 70,000 diagnosed cases of breast cancer in German women in 2012 with over 16,000 deaths resulting from the disease.[5]
"Eisai is pleased that IQWiG has at least in part, and for the majority of patients acknowledged the additional benefit that Halaven may offer to women with metastatic breast cancer. We estimate more than 11,000 women in Germany have had the chance to benefit from treatment with Halaven over the past three years and it is good news that the statistically significant and clinically relevant overall survival benefit has been confirmed again to further increase confidence in this innovative treatment option," commented Gary Hendler, President & CEO, Eisai EMEA and President, Eisai Oncology Global Business Unit.
First approved in 2011, eribulin received Marketing Authorisation Approval (MAA) for earlier use in advanced or metastatic breast cancer from the European Commission on 3 July 2014.
Eisai is dedicated to the discovery, development and production of 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 to better understand 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.[2]
Global Phase III Study 305 (EMBRACE)[3]
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[4]
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.[6],[7]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%).
Eisai in Oncology
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About Eisai Co., Ltd.
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References
1. IQWiG Assessment Report. Available at:
https://www.iqwig.de/de/presse/pressemitteilungen/pressemitteilungen/eribulin-bei-brustkrebs-bei-bestimmten-patientinnen-uberwiegen-positive-effekte-bei-anderen-negative.6407.html
2. 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: October 2014
3. 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
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
5. EUCAN Factsheet Germany. Available at: http://eco.iarc.fr/EUCAN/Country.aspx?ISOCountryCd=276. Accessed: October 2014
6. World Health Organization. Atlas of Health in Europe. 2003. World Health Organization, Regional Office of Europe, Copenhagen, Denmark.
7. Cancer Research UK. Breast cancer incidence statistics.
http://www.cancerresearchuk.org/cancer-info/cancerstats/types/breast/incidence/world . Accessed: October 2014
Date of preparation: November 2014
Job code: Halaven-UK0362
