First Clinical Evidence of Vascular Remodelling Effects of Halaven® (eribulin) in Advanced Breast Cancer Published in the British Journal of Cancer[1]

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Eisai

11 May, 2016, 23:01 GMT

HATFIELD, England, May 12, 2016 /PRNewswire/ --

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

  • Optical imaging confirms differences in oxygen saturation levels between breast tumour tissue treated by eribulin and bevacizumab[2]
  • Biomarker analyses show suppression of cancer cell driver transforming growth factor beta 1 (TGF-1) by eribulin could have favourable anti-angiogenic effect[2]

New data[2] published today in the British Journal of Cancer validate the distinct vascular remodelling activity of Halaven® (eribulin) compared to bevacizumab in breast tumour tissue. Optical imaging techniques for haemodynamic analysis and blood tests for biomarker analysis show that eribulin increases the oxygen saturation of breast tumour tissue and suppresses TGF-1, a driver of cancer progression associated with poor outcomes for women with advanced breast cancer.

"This research sheds light on the biology of vascular remodelling and oxygenation response to eribulin. Contrary to normal cells, cancer cells thrive in a deoxygenated environment. These data show that eribulin is able to increase the density of tiny blood vessels and supply of oxygenated blood to breast cancer tissue. This has the potential to reduce the risk of cancer spreading as the cancer cells can no longer thrive in this environment," comments Shigeto Ueda, Department of Breast Oncology, International Medical Center, Saitama Medical University, Saitama, Japan.

Haemodynamic analysis shows that oxygen saturation levels increase on day seven after treatment with eribulin (p=0.04) while deoxy-haemoglobin concentrations decrease (p=0.01).[2] This trend was not observed for bevacizumab. There was no change in oxygen saturation at day seven (p=0.02), but instead a significant decrease in the concentration of oxy-haemoglobin (p=0.0003) for bevacizumab.[2]

Results of the biomarker analyses show that both eribulin and bevacizumab decrease blood concentrations of VEGF and bFGF.[2] A significant decrease in blood TGF-β1 concentrations is seen in patients treated with eribulin but not bevacizumab (p=0.002).[2] These findings clearly indicate that the mechanism of action of these two agents differs.[2]

In the study, women with Stage 3/4 breast cancer were assigned either eribulin (n=14) or single-agent bevacizumab (N=15). To determine the change in the oxygenated breast tumour tissue, concentrations of oxy-haemoglobin, deoxy-haemoglobin and oxygen saturation were measured using Diffuse optical spectroscopic imaging (DOSI), prior to and seven days after the first infusion. Blood samples were collected for biomarker studies (VEGF, bFGF, and TGF-β1).

"Scientific research and innovation is very important to Eisai. It affords a greater understanding of our treatments and allows us to better serve people living with cancer. These results are of particular importance to us as they help us better understand how eribulin works and the benefit it may offer to women with advanced breast cancer," commented Gary Hendler, Chief Commercial Officer Oncology Business Group, Chairman and CEO EMEA.

Eribulin is currently indicated for the treatment of adult patients with locally advanced or metastatic breast cancer who have progressed after at least one chemotherapeutic regimen for advanced disease.[3] Prior therapy should have included an anthracycline and a taxane unless patients were not suitable for these treatments.[3]

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 has antimitotic effects and promotes vascular remodeling. It effectively inhibits microtubule growth and prevents normal mitotic spindle formation in cells[4] that results in cell death by apoptosis.[3],[5] It also increases microvessel density in the tumour, which increases oxygen flow to deoxygenated (hypoxic) regions.[6]

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  

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.[7] Metastatic disease is an advanced stage of the disease that occurs when cancer spreads beyond the breast to other parts of the body.

TGF-1 is a cytokine (small protein) that performs many cellular functions, including activation of stromal cells (connective tissue cells) in the tumour microenvironment, including endothelial cells, fibroblasts, and immune cells necessary for cancer progression and metastasis.[8],[9] In early stages of breast cancer this cytokine has tumour suppressive effects but in advanced cancer it is linked with increased tumour progression.[8]

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 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. 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;377:914-23

2. Ueda S, et al. In vivo imaging of eribulin-induced reoxygenation in advanced breast cancer patients: a comparison to bevacizumab. Brit J Cancer 2016 Available at: http://www.nature.com/bjc/journal/vaop/ncurrent/pdf/bjc2016122a.pdf Accessed May 2016

3. SPC Halaven (updated March 2016). Available at: http://www.medicines.org.uk/emc/medicine/24382/SPC/Halaven

4. Yoshida T, et al. Eribulin mesilate suppresses experimental metastasis of breast cancer cells by reversing phenotype from epithelial-mesenchymal transition (EMT) to mesenchymal-epithelial transition (MET) states. Br J Cancer. 2014;110:1497-1505

5. Kuznetsov G, et al. Induction of morphological and biochemical apoptosis following prolonged mitotic blockage by halichondrin B macrocyclic ketone analog E7389. Cancer Res 2004;64:5760-66

6. Funahashi Y, et al. Eribulin mesylate triggers vasculature remodeling to reduce the abnormality of tumor microenvironment of human breast cancer models. Submitted. 2014.

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

8. Wendt MK, Tian M, Schiemann WP. Deconstructing the mechanisms and consequences of TGF-beta-induced EMT during cancer progression. Cell and Tissue Res 2012;347:85-101

9. Principe D, et al. TGF-beta: duality of function between tumor prevention and carcinogenesis. Journal of the National Cancer Institute 2014:106:djt369.