SAN ANTONIO, Texas, December 16 /PRNewswire/ --
- First Randomised Phase III Trial in Advanced Breast Cancer to Demonstrate That Endocrine Options Show Favourable Clinical Activity Post NSAI, Even in Patients With Visceral Involvement
For Health Professional Press Only
FOR INTERNATIONAL JOURNALISTS - NOT FOR US MEDIA
AstraZeneca (NYSE:AZN) today announced the first results from a major clinical trial, EFECT (Evaluation of Faslodex vs Exemestane Clinical Trial), at the annual San Antonio Breast Cancer Symposium (SABCS).(1) The data confirm that FASLODEX(TM) (fulvestrant) - an oestrogen receptor antagonist, and the first of a new type of endocrine therapy - is a valuable treatment option for women with hormone-receptor positive (HR+) advanced breast cancer. EFECT is the first clinical trial to explore the use of 'Faslodex' in postmenopausal women who have progressed or recurred after treatment with non-steroidal aromatase inhibitor (NSAI) therapy.
Tamoxifen, previously considered the standard of care for postmenopausal women with HR+ breast cancer, has been displaced in recent years by the more effective and better tolerated aromatase inhibitors (AIs), in both advanced breast cancer and, increasingly, in women at earlier stages of the disease. This has resulted in a 'treatment gap', with a need for physicians to have proven therapeutic options for women who have progressed or recurred on NSAI therapy, to ensure that treatment goals can continue to be achieved.
Dr Stephen Chia, Assistant Professor of Medicine, British Columbia Cancer Agency - Vancouver Cancer Centre commented, "The primary goal of treatment for advanced breast cancer is to slow or halt the progression of the disease without compromising a woman's quality of life. Until recently, treatment options for women progressing or recurring after NSAI therapy were uncertain due to the lack of clinical data in this setting. As more women continue to receive AIs earlier in the treatment sequence, EFECT provides the first large-scale study to examine an alternative endocrine option for this important patient population."
EFECT was designed to examine whether 'Faslodex' was able to extend the time to progression (TTP) in advanced breast cancer patients who had already received NSAI therapy. The 693 women participating in the double-blind phase III trial came from 138 centres in 15 countries, making it one of the largest advanced breast cancer studies in this patient population. Patients were randomised to receive either 'Faslodex' via intramuscular injection loading dose regimen (500 mg day one; 250 mg days 14 and 28, and every 28 days thereafter), or exemestane, a steroidal AI, 25mg tablets once daily in a double-blind, double-dummy design.
At the time of analysis, 288 patients (82.1%) receiving the 'Faslodex' regimen had progressed compared with 299 (87.4%) receiving exemestane with a median TTP of 3.7 months in both groups (HR: 0.963; 95% CI 0.819 - 1.133; p=0.6531).
One of the most encouraging results from EFECT is the Clinical Benefit (CB) rate, which includes both responding patients and those in whom the disease remains stable for at least six months. Long-term disease stabilisation is known to be as beneficial to the patient in terms of overall survival as achieving a complete or partial response.(2,3) Despite a majority of evaluable patients (67%) having visceral metastases - recognised by clinicians as a difficult to treat population - CB rates reached over 30% ('Faslodex' 32.2% vs. exemestane 31.5%). This makes EFECT the first randomised phase III trial to demonstrate that endocrine options show favourable clinical activity post NSAI, even in a certain proportion of patients with visceral involvement.
Furthermore, the EFECT data confirm previous studies(4,5) that show 'Faslodex' is potentially effective and produces durable responses in the advanced breast cancer setting, with a median duration of CB of 9.3 months for 'Faslodex' vs. 8.3 months for exemestane (retrospective analysis, no statistical analysis performed).
"The EFECT data are extremely valuable to clinicians, as they provide a robust foundation upon which treatment decisions can be made in this growing patient population,' added Dr Chia. 'They also confirm fulvestrant as an important additional endocrine option in the overall treatment sequence, particularly as it has shown promising Clinical Benefit rates in a poor prognosis population."
Additional compliance benefits for 'Faslodex'
As a once-monthly intramuscular injection, administered by a nurse or physician, 'Faslodex' offers an alternative to oral, once-daily tablets in the advanced breast cancer setting. A recent study showed that approximately 50% of these patients admitted they sometimes forgot, or chose not to
take their current oral medication.(6) This study also indicated that, from the patients' perspective, while the potential for non-adherence was a major disadvantage of oral treatment, adherence and convenience were the two main points of preference for an injection rather than a tablet.
"A benefit of a once-a-month injection is that it provides women with a greater period of freedom from thinking about their cancer and the treatment needed for it," said Dr Stephen Chia. "It also provides them with reassurance of regular contact with their doctor or nurse. Indeed for some women, once-a-month visits may be a less frequent reminder of their illness than a daily tablet - and we as physicians are assured they are getting the full benefit from treatment."
Cost effectiveness of 'Faslodex' - additional new data
Understanding the cost effectiveness of different sequencing options remains an important consideration when optimising breast cancer treatment. New data from a health economic model, also presented today at SABCS, show that the 'Faslodex' approved dose (250 mg / month), when used as second- or third-line therapy versus a treatment sequence without 'Faslodex', offers a cost effective addition to the overall treatment sequence in advanced breast cancer.(7) By introducing an additional endocrine agent in the treatment sequence, patients can delay or reduce the need for often toxic and expensive chemotherapy.
Future potential of 'Faslodex' in advanced breast cancer
EFECT is one of several major trials ongoing with 'Faslodex' to fully define its optimal role and place in the treatment of hormone receptor-positive breast cancer. This includes investigating 'Faslodex' at higher doses and in combination with other treatments. Because of its unique mechanism of action, 'Faslodex' is an ideal candidate for combination therapy, both with other endocrine agents such as 'Arimidex' (anastrozole) and with novel agents. This potential was supported today by the initial results from a pre-clinical investigation of 'Falsodex' and AvastinTM (bevacizumab) in combination, which demonstrated a marked suppression of breast tumour growth in vivo.
Notes to Editors
- 'Faslodex' is indicated for the treatment of postmenopausal women with oestrogen receptor positive, locally advanced or metastatic breast cancer for disease relapse on or after adjuvant antioestrogen therapy or disease progression on therapy with an antioestrogen.
- 'Faslodex' works by finding oestrogen receptors in the cells and binding to them. In doing so, it blocks oestrogen from binding to them. The binding of 'Faslodex' also causes the receptors to change shape and increases the rate at which they are degraded. 'Faslodex' is given once a month as an intramuscular injection into the buttock.
Breast cancer
- Breast cancer is the most common cancer affecting women. More than 1,150,000 new cases are diagnosed each year, and there are more than 400,000 deaths from the disease annually.(8) Approximately 20% of all women diagnosed with breast cancer have advanced disease (stage IV), where the cancer has spread to other parts of the body. The average period of survival for women with metastatic disease is 18-24 months, but this can vary widely between individual patients.(9)
AstraZeneca
- 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 world's leading pharmaceutical companies with healthcare sales of US$23.95 billion and leading positions in sales of gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infection products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index.
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References
1. Gradishar W, Chia S, Piccart M, on behalf of the EFECT writing committee et al. Fulvestrant versus exemestane following prior non-steroidal aromatase inhibitor therapy: first results from EFECT, a randomized, phase III trial in postmenopausal women with advanced breast cancer. Oral presentation 12 at SABCS, 15 December 2006.
2. Robertson JFR, Williams MR, Todd J et al. Factors predicting the response of patients with advanced breast cancer to endocrine (Megace) therapy. Eur J Cancer Clin Oncol 1989; 23 (1): 469-475.
3. Howell A, Mackintosh J, Jones M et al. The definition of the 'no change' category in patients treated with endocrine therapy and chemotherapy for advanced carcinoma of the breast. Eur J Cancer & Clin Oncol 1988; 24 (10): 1567-1572.
4. Robertson JFR, Osborne CK, Howell A et al. Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma for postmenopausal women: A prospective combined analysis of two multicenter trials. Cancer 2003; 98 (2): 229-238.
5. Mauriac L, Pippen JE, Quaresma Albano J, et al. Fulvestrant (Faslodex(TM)) versus anastrozole for the second-line treatment of advanced breast cancer in subgroups of postmenopausal women with visceral and non-visceral metastases: combined results from two multicentre trials. European Journal of Cancer 2003;39:1228-33.
6. Fallowfield L, Atkins L, Catt S et al. Patients' preference for administration of endocrine treatments by injection or tablets: Results from a study of women with breast cancer. Ann Oncol 2006;17:205-10.
7. Cameron DA, Camidge DR, Gait CF, Hirsch MW. Fulvestrant in the treatment of hormone receptor-positive advanced breast cancer - a cost-effective addition to the treatment sequence. Poster presentation at SABCS, 16 December 2006.
8. Ferlay J, Bray F, Pisani P, et al. GLOBOCAN 2002: Cancer Incidence, Mortality and Prevalence Worldwide IARC CancerBase No. 5. version 2.0, IARCPress, Lyon, 2004.
9. National Institute for Clinical Excellence (NICE). Guidance on cancer services. Improving outcomes in breast cancer. Manual update (www.nice.org.uk ).
