Anastrozole has already been shown, through the 9,366 patient ATAC ('Arimidex', Tamoxifen, Alone or in Combination) trial, to provide significant efficacy benefits compared with tamoxifen, in addition to a more favourable overall tolerability profile in the adjuvant treatment of postmenopausal women with early breast cancer3,4. Furthermore, the ITA (Italian Tamoxifen Anastrozole) trial was the first to show that changing adjuvant therapy from tamoxifen to the aromatase inhibitor, anastrozole after 2 –3 years results in a lower risk of recurrence and fewer serious adverse events compared with continued tamoxifen treatment5. Anastrozole also has recognised benefits over tamoxifen in patients with advanced breast cancer where it is now an established first-choice treatment.6
The new data presented today highlighting the benefits of anastrozole in the preoperative setting come from the PROACT* trial and a prospective combined analysis of the results of the PROACT and IMPACT8, § trials.
In the PROACT trial, 12 weeks' preoperative treatment with anastrozole was shown to have significant benefits compared with the established hormonal therapy, tamoxifen. For patients who were scheduled for a mastectomy or had tumours that were thought to be inoperable at the start of the trial, significantly more were able to undergo less extensive breast-conserving surgery (BCS) in place of mastectomy or to undergo surgery for a previously inoperable tumour, if treated with anastrozole compared with tamoxifen (43% vs. 31% respectively, odds ratio =1.69, p=0.04). These results were supported by a significant difference in the corresponding overall objective response (OR) rates** for these patients (OR for anastrozole = 37%, OR for Tamoxifen = 24%, odds ratio = 1.81, p=0.03).
The combined analysis of the IMPACT and PROACT trials included only the results available from the population common to both trials i.e. those patients who received either anastrozole or tamoxifen alone. Again, for the population with inoperable tumours or requiring mastectomy at study entry (n=344), less extensive surgery became feasible and was actually performed in significantly more patients treated with anastrozole compared with tamoxifen.
- Feasible surgery: anastrozole 47% vs. tamoxifen 35% (odds ratio = 1.67, p=0.021)
- Actual surgery: anastrozole 43% vs. tamoxifen 31% (odds ratio = 1.70, p=0.019)
These new data supporting the use of anastrozole in the preoperative setting are particularly significant when considering the results of an international survey, conducted by the NOP Research Group7, also released for the first time today. In this survey of over 1,700 women (aged 45 and over), 55% said initially that, if diagnosed with breast cancer, they would choose to undergo mastectomy. However, when presented with the option of receiving an effective treatment that could shrink their tumours and allow less extensive (breast-conserving) surgery, nearly half (47%) of women then opted for this alternative in preference to mastectomy. Furthermore, the survey highlighted the immense psychological impact of breast cancer - the fear of losing a breast was among the most common concerns voiced by these women.
Summarising the significance of these results, Professor L Cataliotti, one of the lead investigators for the PROACT trial, of the University degli Studi di Firenze, Italy, said: 'These exciting new data show us that anastrozole is significantly more effective than tamoxifen in downstaging tumours, allowing more patients to undergo breast conserving surgery rather than mastectomy. This is very promising news as the psychological impact of losing a breast should always be considered when reviewing treatment options available to our patients. Furthermore, if inoperable tumours can be made operable, this can have a hugely beneficial effect on a patient's quality of life'. ** assessed by ultrasound T Breast conserving surgery became feasible in those requiring mastectomy at entry or any type of surgery became feasible in those with tumours previously considered inoperable.
The new data from PROACT and the IMPACT / PROACT combined analysis suggest that more women may be able to avoid the devastating consequences of losing their breast if they are treated with anastrozole prior to surgery. Furthermore, if patients are given the choice to receive an effective preoperative treatment to avoid mastectomy, the results of the NOP survey suggest that many of them would prefer that option.
These results will also undoubtedly fuel the growing doubt among clinicians that tamoxifen still remains the most effective endocrine treatment for breast cancer. Anastrozole is the most extensively researched and used aromatase inhibitor, now with over one million patient years experience, and the continued and growing body of evidence suggests that anastrozole can be effective across the whole spectrum of breast cancer treatment.
With this new evidence to support its use in the preoperative setting, anastrozole is becoming recognised as a potential new first-choice treatment in endocrine breast cancer therapy for postmenopausal women.
*About the PROACT trial
The PROACT (Efficacy of PReOperative Arimidex Compared with Tamoxifen) trial evaluated the efficacy of anastrozole versus tamoxifen as preoperative therapy in postmenopausal breast cancer patients who were either scheduled for mastectomy or breast conserving surgery or had inoperable (including locally-advanced), hormone receptor-positive breast tumours. A total of 451 patients were randomised in this double blind study to receive 12 weeks treatment prior to surgery. Some patients also received concomitant chemotherapy. Patients will continue to receive their randomised treatment (adjuvant treatment) following surgery for up to 5 years. As yet only the results from the preoperative part of the study are available and have been presented today.
§About the IMPACT trial
The IMPACT IMmediate Preoperative Arimidex, tamoxifen, or Combined with Tamoxifen) trial involved 330 postmenopausal women with ER+, operable breast cancer including patients with locally-advanced disease (where the tumour has spread locally beyond the confines of the breast itself) and was designed to compare the efficacy of anastrozole and tamoxifen alone and in combination as preoperative therapy. Patients were randomised, in a double-blind study, to treatment with anastrozole, tamoxifen, or a combination of the two drugs. Each treatment was given for 3 months pre-operatively. The results of this trial were first presented at the San Antonio Breast Cancer Congress in December 20038
'Anastrozole ('ARIMIDEX)' is a trademark, property of the AstraZeneca Group of Companies.
Notes to Editors:
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:
- Anastrozole (ARIMIDEX
TM ): the first of a new class of drugs – selective 'aromatase inhibitors'. Anastrozole is now the most extensively researched and used aromatase inhibitor, with over one million patient years experience. Anastrozole is widely used in the treatment of early and advanced breast cancer in post-menopausal women with hormone-sensitive disease. - Fulvestrant (FASLODEX
TM ): a new type of breast cancer therapy (an oestrogen receptor antagonist without known agonist effects). 'Faslodex' is now approved in the European Union for the treatment of postmenopausal women with receptor-positive locally advanced or metastatic breast cancer, for disease relapse or progression on or after therapy with an anti-oestrogen such as tamoxifen. 'Faslodex' has been launched in the USA since May 2002, and more recently in Brazil in July 2003.
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.
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.
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References:
1. Cataliotti L, Buzdar A, Noguchi S, Bines J. Efficacy of PReOperative Arimidex (anastrozole) Compared with Tamoxifen (PROACT) as neoadjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer. Presented at EBCC 2004, Hamburg, Germany
2. Smith I, Cataliotti L, on behalf of the IMPACT and PROACT Trialists. Anastrozole versus tamoxifen as neoadjuvant therapy for oestrogen receptor-positive breast cancer in postmenopausal women: the IMPACT and PROACT trials. Presented at EBCC 2004, Hamburg, Germany
3. The ATAC ('Arimidex', Tamoxifen, Alone or in Combination) Trialists' Group. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: results of the ATAC trial efficacy and safety update analyses. Cancer 2003; 98 (9): 1802-1810.
4. The ATAC ('Arimidex', Tamoxifen, Alone or in Combination) Trialists' Group. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet 2002; 359: 2131-2139.
5. Boccardo F, Rubagotti A, Amoroso D et al. Anastrozole appears to be superior to tamoxifen in women already receiving adjuvant tamoxifen treatment. Breast Cancer Research and Treatment 2003; 82 (Suppl 1):S6-7, Abs 3.
6. Bonneterre J, Buzdar A, Nabholtz JMA et al. Anastrozole is superior to tamoxifen as first-line therapy in hormone receptor positive advanced breast carcinoma: Results of two randomized trials designed for combined analysis. Cancer 2001; 92 (9):2247-2256.
7. NOP Research Group; research conducted 20/10/03 – 19/11/03 (dates vary according to country), 3,435 people surveyed aged 45 and over, telephone/face to face survey (varies according to country)
8. Smith I, Dowsett M on behalf of the IMPACT Trialists. Comparison of anastrozole v tamoxifen alone and in combination as neoadjuvant treatment of oestrogen receptor-positive (ER+) operable breast cancer in postmenopausal women: the IMPACT trial. Breast Cancer Research and Treatment 2003; 82 (Suppl 1):S6-7, Abs 3.