HATFIELD, England, April 17, 2016 /PRNewswire/ --
Studies in Soft Tissue Sarcoma (STS) cell lines elucidate eribulin's molecular activity
FOR EU MEDIA ONLY: NOT FOR SWISS/AUSTRIAN MEDIA
Results from a pre-clinical study of Halaven® (eribulin)[1],[2] in human soft tissue sarcoma (STS) cell lines presented at the American Association for Cancer Research (AACR) Annual Meeting 2016, New Orleans, USA showed antiproliferative activity in xenografts of Ewing's sarcoma, leiomyosarcoma, liposarcoma and fibrosarcoma and improved tumour blood supply in a leiomyosarcoma model. This may decrease the risk of tumour metastatic potential in certain soft tissue sarcomas.[1]
"These data support the antimitotic effect and complex non-mitotic effect of eribulin mesilate in soft tissue sarcoma models. Eribulin showed antiproliferative activity, in vitro and in vivo, and might cause differentiation of STS cells. It also showed improved vascular perfusion, which might be caused by remodelling of tumour vasculature. This may decrease tumour metastatic potency in STS," commented Junji Matsui, Senior Director, Eisai.
The study explored morphological changes in three STS cell lines, gene expression analysis in two cell lines, and blood perfusion in one cell line. Data for blood perfusion show that eribulin may lead to remodelling of the tumour vasculature, resulting in an oxygenated environment. Cancer cells thrive in a deoxygenated (hypoxic) environment and therefore improving tumour perfusion may lead to a decrease in tumour metastatic potency.[3]
"The more we know about the science behind our treatments, the better we are able to offer potential benefit to people with these types of rare cancer. Eisai continues to be committed to working in areas where patients have the greatest need; we call this approach 'ricchi'," commented Gary Hendler, Chief Commercial Officer Oncology Business Group, Chairman and CEO EMEA.
The data presented at the AACR Annual Meeting are consistent with the proposed mode of action of eribulin and offer further insights into the role of eribulin in reducing the metastatic potential in STS.
Only 50% of people with soft tissue sarcomas are expected to live five years[4] 29,000 people are diagnosed with soft tissue sarcomas each year, approximately 1% of all cancers diagnosed in Europe.[5]
In April 2016 the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for eribulin for the treatment of adults with unresectable locally advanced liposarcoma (adipocytic sarcomas) who have received a prior anthracycline-containing regimen. In January 2016 the Food and Drug Administration (FDA) approved eribulin for the treatment of people in the US with unresectable or metastatic liposarcoma who have received a prior anthracycline-containing regimen. Licence was granted in Japan to extend the indication of eribulin to treat patients with soft tissue sarcomas in February 2016
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
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 also induces vascular remodelling, suppresses migration and invasion of cancer cells, and reverses the epithelial-to-mesenchymal transition in many cancer cell lines.
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.[6]
About Soft Tissue Sarcomas
Soft tissue sarcoma is a collective term for a diverse group of malignant tumours. Soft tissue sarcomas are cancers which originate from mesenchymal (connective tissue) cell types - adipocytes and smooth muscle cells.
Unlike other cancers such as non-small cell lung cancer (NSCLC), soft tissue sarcomas are mostly diagnosed with localised disease, and many are amenable to complete surgical removal, yet relapse rates can be as high as 50 percent.[7] Outcomes for patients with advanced disease are poor, with median survival around one year or less. Due to the rarity of these tumours, evidence for prognostic factors is weak and not well understood.[8]
Eribulin in soft tissue sarcoma model - study details[1]
- Anti-proliferation activity of eribulin was examined in 6 human STS cell lines at several doses.
- To analyse the effect of eribulin on morphological change in a test tube, 3 human STS cell lines were treated with eribulin at 1, 3, and 10 nmol/L for 7 days. Gene expression change was analysed.
- For tumour blood perfusion (the process of delivery of nutrients to arterial blood to a capillary bed in the tissue) analysis in SK-LMS-1 xenografts, eribulin was administered at doses of 0.38, 0.75, and 1.5 mg/kg and tumour blood perfusion was calculated 5 days after the administration.
- Eribulin showed anti-proliferation activity in vitro and in vivo against all 6 cell lines in a dose dependent manner. Eribulin showed significant antitumor activity against 4 xenografts (Ewing's sarcoma, leiomyosarcoma, liposarcoma and fibrosarcoma) in a dose dependent manner. Eribulin treatment for 7 days induced apparent morphological change in 3 cell lines. In addition, eribulin significantly enhanced tumour blood perfusion compared to vehicle control 5 days after the administration in leiomyosarcoma xenografts at all doses. Eribulin might cause differentiation of STS cells and remodelling of tumour vasculature to enhance tumour blood perfusion.
- Eribulin showed mitotic effect and non-mitotic effect, which may decrease tumour metastatic potency in STS, as well in breast cancer.
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. Kawano S, et al. Antimitotic effect and complex of non-mitotic effect on tumor biology of eribulin mesilate in soft tissue sarcoma model. AACR 2016, New Orleans, USA; #344
2. Kawano S, et al. Antimitotic and Non-mitotic Effects of Eribulin Mesilate in Soft Tissue Sarcoma. Anticancer Research 2016; 36; 1553-1562
3. Kevin L Bennewith and Shoukat Dedhar. Targeting hypoxic tumour cells to overcome metastasis. BMC Cancer 2011;11:504
4. National Cancer Institute - http://www.cancer.org/cancer/sarcoma-adultsofttissuecancer/detailedguide/sarcoma-adult-soft-tissue-cancer-survival-rates
5. ESMO Guidance. Available at: http://annonc.oxfordjournals.org/content/25/suppl_3/iii102.full.pdf+html Accessed: November 2015
6. SPC Halaven (updated November 2015). Available at: http://www.medicines.org.uk/emc/medicine/24382 Accessed: March 2016
7. R. Pollock. Soft Tissue Sarcomas, A Volume in the American Cancer Society Atlas of Clinical Oncology Series. 2012
8. Fletcher et al. World Health Organization Classification of Tumours of Soft Tissue and Bone (4th Edition). Lyon: IARC Press, 2013
