Halaven® (eribulin) Shows Significant Overall Survival Benefit in Liposarcoma and Improved Quality Of Life in Two Subtypes of Soft Tissue Sarcoma in New Analyses from a Phase III Study

HATFIELD, England, June 6, 2016 /PRNewswire/ --


New data presented at the American Society of Oncology Annual Meeting show significant anti-tumour activity for eribulin in liposarcoma and for liposomal formulation in solid


Eribulin is an active agent against liposarcoma according to tumour subtype analyses[1] of a Phase III trial[2] that examine efficacy and safety of eribulin compared with dacarbazine, presented today at the American Society of Clinical Oncology Annual Meeting. There is a significant improvement in overall survival compared with dacarbazine (15.6 versus 8.4 months; HR=0.51, p=0.001) and progression free survival (2.9 versus 1.7 months; HR=0.52, p=0.002) for patients with liposarcomas in these pre-planned analyses.[1]

"As previously reported in the full data set in liposarcoma and leiomyosarcomas 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. There are very few effective treatments available for liposarcomas, so the findings of these sub analyses are important for these patients," comments Patrick Schöffski, Head of the Department of General Medical Oncology, University Hospitals Leuven, Belgium.

Each year 29,000 people are diagnosed with soft tissue sarcomas, approximately 1% of all people diagnosed with cancer in Europe.[3] Only 50% of people with soft tissue sarcomas are expected to live five years.[3] Liposarcomas account for 16 to 18% of all malignant soft tissue sarcomas and arise from fat cells anywhere in the body.[4],[5]

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.[6] In May 2016, the European Commission approved a variation to the terms of the Marketing Authorisation of eribulin for the treatment of adult patients with unresectable liposarcomas who have received prior anthracycline containing therapy (unless unsuitable) for advanced or metastatic disease.

These Tumour subtype-specific analyses examine the safety and tolerability of eribulin versus dacarbazine in 143 patients with liposarcoma, representing 32% of the total study population (n=452). An overall survival benefit is observed with eribulin versus dacarbazine regardless of liposarcoma histology (dedifferentiated is 18.0 vs 8.1 months, HR=0.43; myxoid/round cell is 13.5 vs 9.6 months, HR=0.79; pleomorphic is 22.2 vs 6.7 months, HR=0.18).[1]

Eribulin has a toxicity profile consistent with prior experience, with no unexpected or new safety findings. Treatment with eribulin is well tolerated and the most common all grade adverse events were alopecia, fatigue, neutropenia, and nausea. Adverse events of greater than or equal to grade 3 occur in 63% of patients in the eribulin arm and 51% of patients in the dacarbazine arm.[1]

Study 309 is a randomised, open-label multicentre Phase III study comparing the efficacy and safety of eribulin to dacarbazine in 452 patients (aged 18 or over) with leiomyosarcomas or liposarcomas.[2] 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.

Eribulin is a microtubule-dynamics inhibitor, a structurally modified analogue of halichondrin B, originally isolated from the marine sponge Halichondria okadai. Its mode of action is distinct from other tubulin inhibitors and involves binding to specific sites on the growing positive ends of microtubules to inhibit their growth. Recent data for blood perfusion show that eribulin may lead to remodelling of tumour vasculature, resulting in reoxygenation of deoxygenated (hypoxic) tumour areas.[7] A hypoxic tumour microenvironment significantly affects progression and management of cancer and therefore improvement of tumour perfusion may lead to a decrease in tumour metastatic potency.[8]

In exploratory analyses of study 309 that examine differences in health-related quality of life between eribulin and dacarbazine for those patients with disease progression,[9] there are notable increases in symptom severity among patients treated with dacarbazine compared to patients in the eribulin arm. Quality of life scores at baseline are equivalent for both arms. Patients on dacarbazine had a statistically significant lower global health status compared to those on eribulin (56.1 vs 62.1; p=0.0083) and a statistically significant physical function (63.9 vs 73.3; p=0. 0022) as well as worse nausea/vomiting (p=0.0009) and appetite loss (p=0.001).[9]

Of the 452 patients randomised to Study 309, 400 patients with progressive disease are included in these evaluations. Health-related Quality of life (HRQoL) is determined using the European Organisation for Research and Treatment of Cancer QLQ-C30 (EORTC QLQ-C30) and the EuroQol Five Dimension Scale (EQ-5D-3L).[9]

"Eribulin has now demonstrated an overall survival benefit in two solid tumour types. This data is of significant importance, particularly given that eribulin is the first and only treatment to demonstrate an overall survival benefit over an active comparator in soft tissue sarcomas. Eisai continue to be committed to exploring how we can deliver innovative treatments like eribulin for the benefit of people who live with cancer" comments Gary Hendler, Chief Commercial Officer Eisai Oncology Business Group, Chairman and CEO Eisai EMEA.

Phase 1 multicenter, open label study to establish the maximum tolerated dose of two administration schedules of eribulin liposomal formulation in patients with solid tumours [10] 

The investigative liposomal formulation of eribulin shows promise and is well tolerated in patients with breast cancer (5/10 partial responses, 3/10 stable disease).[10]

Eribulin liposomal formulation is given in a dose escalation manner to 58 eligible patients in either schedule 1 (day 1 of a 21-day cycle) or schedule 2 (day 1 and 15 of a 28-day cycle). Dose limiting toxicities for schedule 1 are grade 4 hypophosphataemia and grade 4 increased ALT/AST. Dose-limiting toxicities for schedule 2 are grade 4 febrile neutropenia, grade 3 increased ALT/AST, and grade 4 neutropenia. The maximum tolerated dose is 1.4 mg/m2 in schedule 1 and 1.5 mg/m2 in schedule 2, which was the dose and schedule used for an expansion phase in 23 patients with solid tumours (endometrial, ovarian, or HER2-negative breast cancer). [10]

Treatment emergent adverse events (TEAEs) included peripheral neuropathy and neutropenia. TEAEs of grade greater than or equal to 3 occur in 55% of patients with schedule 1 and in 39% of patients with schedule 2. Eribulin liposomal formulation exposure was dose dependent and half-life is approximately 35 hrs. [10]

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(R) (eribulin)  

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]

In May 2016, the European Commission approved a variation to the terms of the Marketing Authorisation of eribulin for the treatment of adult patients with unresectable liposarcomas who have received prior anthracycline containing therapy (unless unsuitable) for advanced or metastatic disease.

In June 2016, Eisai's subsidiary in the Philippines HI-Eisai Pharmaceutical Inc., received approval for eribulin mesylate for the treatment of soft tissue sarcoma in the Philippines.

About Soft Tissue Sarcomas 

Soft tissue sarcoma is a collective term for a diverse group of malignant tumours. 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.[5] 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.[11]

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. 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.[12]

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.


1. Chawla S, et al. Subtype specific activity in liposarcoma (LPS) patients (pts) from a phase 3, open label, randomised study of eribulin (ERI) versus dacarbazine (DTIC) in patients with advanced LPS and leiomyosarcoma (LMS). American Society for Clinical Oncology annual meeting 2016; Abstract # 11037

2. Schöffski P, et al. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. The Lancet. 2016; DOI: http://dx.doi.org/10.1016/S0140-6736(15)01283-0

3. ESMO Guidance: http://www.esmo.org/Guidelines/Sarcoma-and-GIST/Soft-Tissue-and-Visceral-Sarcomas . Accessed May 2016

4. Ouni F, et al. Liposarcoma of the extermities: MR imaging features and their correlation with pathologic data. Orthopaedics & Traumatology: Surgey & Research 2010; 96; 876-883

5. Macmillan. What are soft tissue sarcomas? Available at: http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Softtissuesarcomas/Aboutsofttissuesarcomas/Softtissuesarcomas.aspx . Accessed: November 2015

6. SPC Halaven (updated November 2015). Available at: http://www.medicines.org.uk/emc/medicine/24382 Accessed: May 2016

7. Kawano S, et al. Antimitotic and Non-mitotic Effects of Eribulin Mesilate in Soft Tissue Sarcoma. Anticancer Research 2016; 36; 1553-1562

8. Kevin L Bennewith and Shoukat Dedhar. Targeting hypoxic tumour cells to overcome metastasis. BMC Cancer 2011;11:504

9. Hudgens S, et al. Evaluation of quality of life at progression in patients with soft tissue sarcoma. American Society for Clinical Oncology annual meeting 2016; Abstract # 11015

10. Zubairi I, et al. Phase 1 multicenter, open label study to establish the maximum tolerated dose (MTD) of two administration schedules of E7389 (eribulin) liposomal formulation in patients (pts) with solid tumours. American Society for Clinical Oncology annual meeting 2016; Abstract # 2524

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

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


CONTACT: Media Enquiries: Eisai, Cressida Robson / Ben Speller, +44(0)7908314 155/+44(0) 7908 409416, Cressida_Robson@eisai.net /Ben_Speller@eisai.net; Tonic Life Communications, Alex Davies / CallumHaire, +44 (0)7716 324722 / +44 (0)7867 429 637, Alex.Davies@toniclc.com /Callum.Haire@toniclc.com

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