Faslodex provides new hope for women with advanced breast cancer whose disease has progressed following prior anti-oestrogen treatment

European Breast Cancer Congress, Hamburg: AstraZeneca announced today the first European launches of its new breast cancer drug FASLODEXTM (fulvestrant) in Germany and Sweden, with Austria following imminently.

The novel drug - an oestrogen receptor antagonist with no agonist effects - is for the treatment of advanced breast cancer in postmenopausal women whose cancer has progressed on previous anti-oestrogen treatments such as tamoxifen. Fulvestrant has been launched in the USA since May 2002, and more recently in Brazil in July 2003.

Fulvestrant was approved for launch in the European Union (EU) on 12 March 2004, making it the first new type of hormonal treatment for oestrogen receptor-positive breast cancer to be approved in the EU since 1995. The launch of the drug in Germany, Sweden and Austria therefore provides new hope to the thousands of women suffering from advanced disease in these countries. Further launches throughout Europe are expected during the course of this year.

Commenting on the launch, Professor Kurt Possinger, Head of the Oncology Department at Humboldt University of Berlin, Germany, explains, \"The availability of ’Faslodex’ in these countries is very exciting as women who have progressed on prior tamoxifen therapy now have a new additional and effective treatment option which may help extend the window of endocrine therapy and delay the use of cytotoxic chemotherapies with their well-recognised and unwanted side-effects .

In addition, unlike other endocrine therapies used in postmenopausal women, ’Faslodex’ is a once-monthly injection which enables clinicians to have greater contact with their patients to review progress and free women of the worry of remembering to take a daily tablet, allowing them to focus on their life and not their illness.\"

Breast cancer affects 1 in 9 women at some point in their lives and although many tumours are detected early and treated successfully, a large number of women still go on to be diagnosed with advanced breast cancer.

The goal of treatment for these women is to achieve an effective disease response and to enable the patient to maintain good quality of life for as long as is feasibly possible. Hormonal agents such as aromatase inhibitors and tamoxifen are standard therapy in postmenopausal women with advanced breast cancer, providing an effective and well-tolerated treatment option. However, in time tumour cells can grow resistant to treatment with these hormonal therapies and as a result there is a need for new agents to which tumours are not resistant.

Fulvestrant is an exciting new type of therapy, which brings new choices for women with advanced disease, extending the sequence of ’patient-friendly’ hormonal therapies that can be used to control the disease.

Fulvestrant works differently to any other treatment available, although like the other hormonal therapies it interferes with the effect of the hormone ’oestrogen’ on tumour growth. Many breast cancers are dependent on the presence of oestrogen to grow.

Of the current therapies, aromatase inhibitors (e.g. ARIMIDEXTM (anastrozole)) work by reducing the amount of oestrogen in a woman’s body, and tamoxifen (an anti-oestrogen) blocks oestrogen receptors. However, tamoxifen also mimics some of the actions of oestrogen, which can result in unwanted side effects. In contrast, fulvestrant works by blocking and removing the oestrogen receptors in the breast cancer cells and, unlike tamoxifen, does not mimic the actions of oestrogen.

Fulvestrant offers durable responses and has tolerability benefits compared with aromatase inhibitors and tamoxifen. Fulvestrant is effective following disease progression on prior anti-oestrogen and aromatase inhibitor therapy, in addition both therapies are effective following fulvestrant therapy.

Fulvestrant therefore meets a key unmet need for women with advanced breast cancer, since it can be added in to the sequence of well-tolerated hormonal therapies and may delay the need to resort to cytotoxic chemotherapies with their well-recognised side effects.

The key benefits of fulvestrant are likely to be welcomed by these women and their physicians, since it provides an important new treatment option for patients. These benefits include the following:

Fulvestrant has been shown to be an effective and well-tolerated treatment without any of the side effects commonly associated with cytotoxic chemotherapy, and to offer some tolerability benefits over the aromatase inhibitors and tamoxifen.

Commonly reported side effects with fulvestrant have included hot flushes, nausea, weakness and headache. These occurred with similar incidence to anastrozole.

Fulvestrant was at least as effective as anastrozole in clinical trials to establish its efficacy. Unlike many other hormonal therapies, fulvestrant is given once monthly as a slow release formulation administered by an intramuscular injection.

As such, fulvestrant brings welcome compliance benefits for some women, and for the first time offers a monthly alternative to the once-daily tablet.

Fulvestrant is approved with the same licence throughout the EU, Norway and Iceland, and will also receive approval in the additional countries added to the EU member states in May 2004.

The approval of fulvestrant is based on data from two major trials involving over 800 women, which compared the efficacy and tolerability of fulvestrant to that of anastrozole in the treatment of advanced breast cancer in postmenopausal women whose disease had relapsed on previous hormonal therapies. These trials showed that fulvestrant was at least as effective as anastrozole with respect to efficacy and was also very well tolerated. 1, 2

’Faslodex’ is a trademark, the property of the AstraZeneca group of companies.

AstraZeneca continues its tradition of research excellence and innovation in oncology that led to the development of its current anti-cancer therapies including ’ARIMIDEX’ (anastrozole), ’CASODEX’ (bicalutamide), ’FASLODEX’ (fulvestrant), ’NOLVADEX’ (tamoxifen), ’ZOLADEX’ (goserelin), ’TOMUDEX’ (raltitrexed) and ’IRESSA’ (gefitinib) as well as a range of novel targeted products such as anti-proliferatives, anti-angiogenics, vascular targeting and anti-invasive agents.

AstraZeneca is also harnessing rational drug design technologies to develop new compounds that offer advantages over current cytotoxic and hormonal treatment options. The company has over 20 different anti-cancer projects in research and development.

Since AstraZeneca released its first anti-cancer drug, ’Nolvadex’ (tamoxifen), more than 25 years ago, investment in research has led to the discovery of new anti-cancer agents and other innovative therapeutic strategies which give AstraZeneca an extensive portfolio of developmental agents to complement the established product range.

AstraZeneca’s product range for breast cancer, include the following: 1973: Tamoxifen (NOLVADEXTM): a well-tolerated, oral anti-oestrogen. Now the most widely prescribed agent for the treatment of all stages of breast cancer worldwide. 1990: Goserelin (ZOLADEXTM): a well-tolerated and widely-prescribed LHRH analogue, administered by sub-cutaneous injection every 28 days, which reduces sex hormone production.

Goserelin is now used in the treatment of early and advanced breast cancer in pre-menopausal women with hormone-sensitive disease. 1995: Anastrozole (ARIMIDEXTM): the first of a new class of drugs - selective ’aromatase inhibitors’ - now widely used in the treatment of early and advanced breast cancer in post-menopausal women with hormone sensitive disease. 2002: Fulvestrant (FASLODEXTM): a new type of breast cancer therapy (an oestrogen receptor antagonist without known agonist effects). It is now available in the USA and Brazil for the treatment of hormone receptor positive metastatic breast cancer in postmenopausal women with disease progression following antioestrogen therapy such as tamoxifen. Approved in Europe in 2004.

AstraZeneca is a major international healthcare business engaged in the research, development, manufacture and marketing of prescription pharmaceuticals and the supply of healthcare services. It is one of the top five pharmaceutical companies in the world with healthcare sales of over $18.8 billion and leading positions in sales of gastrointestinal, oncology, cardiovascular, neuroscience and respiratory products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global and European) as well as the FTSE4Good Index.

Fulvestrant, marketed as ’FASLODEX’, is licensed for the treatment of post-menopausal women with oestrogen receptor-positive locally advanced or metastatic breast cancer, for disease relapse on or after anti-oestrogen therapy or disease progression on therapy with an anti-oestrogen. Fulvestrant is administered as a once a month intramuscular injection, which may offer compliance benefits and since it is a hormonal treatment, it does not cause the side effects commonly associated with chemotherapy.

Fulvestrant has been available in the USA since May 2002, for the treatment of hormone receptor positive metastatic breast cancer in postmenopausal women with disease progression following anti-oestrogen therapy. In that time, fulvestrant has seen rapid uptake in clinical practice beyond expectation and has helped thousands of postmenopausal women with advanced breast cancer.

Fulvestrant works differently to other anti-oestrogen agents for breast cancer, in that it binds to the oestrogen receptor in the breast cancer cell, and this interaction results in loss of the cellular oestrogen receptor (down-regulation). Fulvestrant attacks cancer cells that have grown resistant to current anti-oestrogen treatment options.

Thousands of women are diagnosed with advanced breast cancer each year - advanced breast cancer is diagnosed when cancer that is originally confined to the breast is found in other parts of the body. More specifically, a woman is considered to have advanced disease when breast cancer cells also form a tumour in places such as the lungs, liver or bones. In locally advanced disease, the cancer involves spread to the tissues surrounding the breast, such as underlying muscles or skin, but not to distant organs. Extensive lymph node involvement is also counted as locally advanced disease.

1. C.K. Osborne, et al. Double-Blind, Randomized Trial Comparing the Efficacy and Tolerability of Fulvestrant Versus Anastrozole in Postmenopausal Women With Advanced Breast Cancer Progressing on Prior Endocrine Therapy: Results of a North American Trial. Journal of Clinical Oncology 2002; 20(16).

2. A. Howell, et al. Fulvestrant, Formerly ICI 182,780, Is as Effective as Anastrozole in Postmenopausal Women With Advanced Breast Cancer Progressing After Prior Endocrine Treatment. Journal of Clinical Oncology 2002; 20(16).