HATFIELD, England, May 30, 2015 /PRNewswire/ --

Data from pivotal Phase III study for investigational use of eribulin presented during oral session at the American Society of Clinical Oncology (ASCO) Annual Meeting 2015 

A pivotal Phase III trial (Study 309) of Halaven^® (eribulin)^[1] in patients with liposarcomas and leiomyosarcomas (two of the most common forms of sarcoma), is today presented at ASCO 2015. The study met its primary objective for overall survival benefit (OS) for investigational use in patients treated with eribulin compared to dacarbazine. Median OS for eribulin was 13.5 months versus 11.5 months for dacarbazine representing a significant benefit (HR 0.768; 95% C1 0.618-0.954; p=0.017), meaning that patients treated with eribulin may have a 23% reduction in the risk of death.^[2]

These data are to be presented at the 51^st Annual Meeting of the American Society of Clinical Oncology during an oral session on Monday 1 June 2015 at 15:48 CST (Abstract No. LBA10502).^[2]

Study 309 is a randomised, open-label multicentre Phase III study comparing the efficacy and safety of eribulin in 452 patients (aged 18 or over) to dacarbazine.  Patients included in the study had leiomyosarcomas or liposarcomas. Patients with locally advanced or relapsed and metastatic soft tissue sarcomas who showed disease progression following standard therapies must have included an anthracycline and at least one other additional regimen.^[1]

An additional study endpoint included progression-free survival (PFS) at 12 weeks.  While there was a numerical difference between arms favouring eribulin versus dacarbazine (33% vs 29%) this was not statistically significant. Median PFS was 2.6 months in both arms.

"This is the first and only randomised controlled trial of a single agent systemic therapy to demonstrate an improvement in overall survival in people previously treated for soft tissue sarcomas at this stage of the disease. The study population represents a high risk group of patients with co-morbid conditions, multiple prior drug regimens, and intermediate to high tumour grade, and therefore these results represent an important breakthrough in this disease," comments Patrick Schöffski, Head of the Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium.

"We are proud that such an important study was originated by Eisai, particularly given the rare and hard to treat nature of soft tissue sarcomas. Eribulin is a drug that was discovered and developed by Eisai and we are pleased to see it being examined in new ways to potentially benefit people living with soft tissue sarcomas", commented Alton Kremer, Deputy President, Global Head Clinical Development, Oncology PCU.

Soft tissue sarcomas are cancers that develop from cells in the soft, supporting tissues of the body such as fat, muscle, nerves, fibrous tissues and blood vessels.^[3] Leiomyosarcomas are one of the more common types of sarcoma to develop in adults. They develop from cells called smooth muscle and can start anywhere in the body.^[3]  Liposarcomas (adipocytic sarcomas) arise from fat cells and can also occur anywhere in the body. Leiomyosarcomas and liposarcomas make up approximately 30% of all cases of soft tissue sarcomas.^[4]

While soft tissue sarcomas are relatively rare, there remains an unmet medical need for patients who often fail to respond to treatment and therefore have a poor prognosis.^[9] In Europe, approximately 29,000 people will be diagnosed with soft tissue sarcomas each year.^[5] Approximately 11,930 cases of soft tissue sarcomas will be diagnosed in the United States this year.^[6] In Japan, approximately 2,000 cases of soft tissue sarcomas are diagnosed each year.^[7],[8]

"Study 309 represents the second Phase 3 trial in which eribulin as a single agent has demonstrated an overall survival benefit in a distinct solid tumour type. We are proud of our ongoing research efforts that may expand the value of existing therapies to address the unmet medical needs of patients, especially those with rare and orphan cancers, across the oncology spectrum," commented Kenichi Nomoto, President, Oncology Product Creation Unit at Eisai Inc.

Eribulin had a toxicity profile consistent with prior experience, with no unexpected or new safety findings. In this study, the most common adverse events observed in the eribulin arm were neutropenia, fatigue, nausea, alopecia and constipation.^[1]

Eisai intends to submit applications during the first half of the fiscal year of 2015 to the regulatory authorities in multiple countries including the United States, Europe and Japan to expand the indication of eribulin to include soft tissue sarcomas.

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  

About Soft Tissue Sarcomas 

Soft tissue sarcoma is a collective term for a diverse group of malignant tumours.

Leiomyosarcomas are one of the more common types of sarcoma to develop in adults. They start from cells in a type of muscle tissue called smooth muscle. Smooth muscles are involuntary muscles that we have no control over. They are found in the walls of muscular organs like the heart and stomach, as well as in the walls of blood vessels throughout the body. This means that leiomyosarcomas can start anywhere in the body. Common places are the walls of the womb (uterus), the trunk of the body, and the arms and legs.^[3]

Liposarcomas (adipocytic sarcomas) arise from fat cells and can occur anywhere in the body. Incidence rates in males are twice as high as those in females.^[6] Leiomyosarcomas and liposarcomas make up approximately 30% of all cases of soft tissue sarcomas.^[4]

The annual incidence of soft tissue sarcoma is approximately 50 cases per million of the population globally. 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.^[9] Outcomes for patients with advanced disease are poor, with median survival around 1 year or less. Due to the rarity of these tumours, evidence for prognostic factors is weak and not well understood.^[10]

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.^[11]

Global Phase III Clinical Study 309^[1]

Study 309 is a randomised, open-label multicentre Phase III study comparing the efficacy and safety of eribulin vs dacarbazine in adults with one of two soft tissue sarcoma subtypes (adipocytic sarcoma or leiomyosarcoma) previously treated with an anthracycline and at least two prior regimens after anthracycline failure.

The primary endpoint of the study was to compare overall survival between both treatment arms, and the additional endpoints included progression free survival and quality of life.^[1]

Patients were aged ≥18 years with advanced high/intermediate grade leiomyosarcoma or dedifferentiated, myxoid, round cell or pleomorphic variants of adipocytic sarcoma (ADI) incurable by surgery and/or radiotherapy were enrolled. Patients had ECOG status ≤2 and had received ≥2 standard systemic treatment regimens including an anthracycline. Patients were randomized 1:1 to eribulin (1.4 mg/m2, IV on D1 and D8) or dacarbazine (850-1200 mg/m2, IV on D1) every 21 days until disease progression.

Overall, 452 patients (67% female; 79% <65 years) were randomized (228 eribulin; 224 dacarbazine). Median OS for eribulin and dacarbazine was 13.5 and 11.5 months, respectively (HR=0.768, 95% CI 0.618-0.954; P=0.017). PFS was 2.6 months in both arms (HR=0.877, 95% CI 0.710-1.085; P=0.229). PFS rate at week 12 was 33% and 29% for eribulin and dacarbazine, respectively. Eribulin had a toxicity profile consistent with prior experience, with no unexpected or new safety findings. In this study, the most common adverse events observed in the eribulin arm were neutropenia, fatigue, nausea, alopecia and constipation, which is consistent with the known profile of eribulin.

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. Clinicaltrials.gov https://clinicaltrials.gov/ct2/show/NCT01327885?term=halaven+soft+tissue+sarcoma&rank=2 Accessed: May 2015

2. Schöffski P et al. Randomized, open-label, multicenter, phase 3 study of eribulin versus dacarbazine in patients (pts) with leiomyosarcoma (LMS) and adipocytic sarcoma (ADI).  American Society of Clinical Oncology annual meeting 2015; Abstract #LBA10502

3. Macmillan. What are soft tissue sarcomas? http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Softtissuesarcomas/Aboutsofttissuesarcomas/Softtissuesarcomas.aspx . Accessed: May 2015

4. Cancer Research UK, Soft Tissue Sarcoma Incidence Statistics: http://www.cancerresearchuk.org/cancer-info/cancerstats/types/soft-tissue-sarcoma/incidence/ Accessed: May 2015

5. ESMO Guidance: http://annonc.oxfordjournals.org/content/25/suppl_3/iii102.full.pdf+html Accessed: May 2015

6. National Cancer Institute http://www.cancer.gov/cancertopics/pdq/treatment/adult-soft-tissue-sarcoma/HealthProfessional/page1 . Accessed May 2015

7. Matsuda S., et al. Soft-Tissue Sarcoma Surveillance Counterpoint: Japan. Current Clinical Oncology. 2013; 233-34

8. H. Tsujii, et al. Carbon-Ion Radiotherapy: Principles, Practices, and Treatment Planning. Springer. 2014; (XII)312:37

9. R. Pollock. Soft Tissue Sarcomas: A Volume in the American Cancer Society Atlas of Clinical Oncology Series. 2012

10. Fletcher et al. World Health Organization Classification of Tumours of Soft Tissue and Bone (4th Edition). Lyon: IARC Press, 2013.

11. 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: May 2015

Date of preparation: May 2015

Job code: Oncology-UK0035

SOURCE Eisai