The National Institute for Health and Clinical Excellence (NICE) today issued draft guidance on Halaven? (eribulin) for public consultation. The draft guidance does not recommend NHS (National Health Service) funding of eribulin, a treatment for locally advanced or metastatic breast cancer.

Eribulin is a novel treatment indicated for patients with locally advanced or metastatic breast cancer whose disease has progressed after at least two chemotherapeutic regimens for advanced and metastatic disease.[1] It was launched in the UK in April 2011 and some patients have already started to benefit from treatment. Before the approval of eribulin in the EU, no single treatment has demonstrated a statistically significant prolongation of median overall survival as shown in the clinical trial.[2]

An innovative treatment option
“We are hugely disappointed with the draft guidance issued by NICE. It has not recommended an innovative treatment for a vulnerable group of women with heavily pre-treated locally advanced or metastatic breast cancer, with a proven overall survival benefit,” commented Nick Burgin, European Director of Market Access, Eisai. He adds; “Despite the UK price of eribulin currently being the lowest in the world, and a further patient access scheme agreement with the Department of Health which makes eribulin available at a discounted price, and unique real-world comparative data that has demonstrated overall survival, NICE’s unwillingness to approve this treatment is a real surprise.”

Anthracyclines and taxanes
There is a clear unmet need for treatments that improve overall survival for women with locally advanced or metastatic breast cancer, particularly those who do not respond or become refractory to treatments such as anthracyclines and taxanes and, in many cases, capecitabine.[3]

Regulatory status
Eribulin is approved in the European Union, USA, Switzerland, Japan, and Singapore. Eribulin is currently commercially available in Austria, Denmark, Finland, Germany, Netherlands, Norway, Portugal, Spain, Sweden, Singapore, Switzerland, United Kingdom, and the USA and will become commercially available in Japan on 19 July 2011.

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NICE draft guidance
The draft guidance is based on the Phase III data showing a median overall survival benefit of 13.1 months for patients receiving eribulin compared to 10.6 months for patients receiving ‘treatment of physician’s choice’ (TPC).[4] The side-effect profile of eribulin was expected and manageable. The most commonly reported adverse reactions among patients were asthenia (fatigue), neutropenia, alopecia (hair loss), peripheral neuropathy (numbness and tingling in arms and legs), nausea and constipation.[1] Limited inference can be drawn from direct comparison of safety between patients treated with eribulin and those treated with TPC, as each of the therapies in the TPC group has a distinct safety profile. However, comparisons between eribulin and TPC showed that serious adverse events occurred in 25% of patients on eribulin and 26% of those on TPC, and adverse events leading to therapy discontinuation occurred in 13% of eribulin patients and 15% of TPC patients.

No unexpected side-effects
Professor Neville Davidson, Consultant Oncologist commented; “Having treated patients with eribulin, there were no unexpected side-effects in comparison with other treatments options in heavily pre-treated patients with locally advanced or metastatic breast cancer.”

Pre-planned analysis of patients from geographical North America, Western Europe and Australia (region 1) best represent how patients in the UK are managed and showed a significant overall survival benefit of eribulin over TPC of 3.0 months, nominal p=0.031 (updated analysis).[4] Eisai, the company developping the drug, is currently evaluating the ACD and will be responding to the preliminary guidance to reverse the recommendations so that more patients can benefit from treatment with eribulin.

Clinical trials
Global Phase III Clinical Study (EMBRACE) EMBRACE was an open-label, randomised, global, multi-centre, parallel two-arm study designed to compare overall survival in patients treated with eribulin versus a Treatment of Physician”s Choice (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 patients with metastatic breast cancer 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 (97%) of patients in the TPC arm received chemotherapy.[2]

Lifetime risk of MBC
Metastatic Breast Cancer Breast cancer is now the most common cancer in the UK and the lifetime risk of being diagnosed with breast cancer is 1 in 8 for women in the UK.[5] In 2008, almost 47,700 women were diagnosed with breast cancer, around 130 women a day.[4]

Metastatic disease at the time of diagnosis
Metastatic breast cancer is an advanced stage of the disease that occurs when cancer spreads beyond the breast to other parts of the body. Approximately five percent of women with breast cancer will have metastatic disease at the time of diagnosis[6] and others with local and regional disease may eventually develop metastatic disease.[7] An estimated 13 percent of women presenting with metastatic breast cancer will survive beyond five years.[5] Halaven(R) (eribulin) Eribulin is a non-taxane, microtubule dynamics inhibitor indicated for the treatment of patients with breast cancer who have previously received at least two chemotherapeutic regimens for metastatic disease and whose prior therapy should have included an anthracycline and a taxane.[3] Eribulin belongs to a class of antineoplastic agents, the halichondrins, which are natural products, isolated from the marine sponge Halichondria okadai. It is believed to work by inhibiting the growth phase of microtubule dynamics without affecting the shortening phase and sequesters tubulin into non-productive aggregates.

For more information:
[1] Summary of Product Characteristics (SPC) Halaven (Eribulin). Last accesses July 19, 2011.
[2] Jassem J, Carroll C, Ward SE, Simpson E, Hind D. The clinical efficacy of cytotoxic agents in locally advanced or metastatic breast cancer patients pretreated with an anthracycline and a taxane: a systematic review. Eur J Cancer. 2009 Nov;45(16):2749-58.
[3] National Institute for Health and Clinical Excellence. NICE clinical guideline 81: Advanced breast cancer: diagnosis and treatment – full guideline. 2009.
[4] 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
[5] Cancer Research UK. Cancer Statistics – Key Facts. Last accesses April 1, 2011
[6] Cancer Research UK. Statistics and outlook for breast cancer. Last accesses April 1, 2011
[7] Cancer Research UK. Statistics and outlook for breast cancer. Last accesses April 1, 2011.

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