The overall results of the ATAC study, involving over 9,300 post- menopausal women, have already clearly shown that anastrozole is significantly more effective than tamoxifen in terms of improving disease-free survival in early breast cancer. This means that it was more likely to prevent the cancer recurring, not only in the same breast, but also in the other breast and elsewhere in the body. In addition, anastrozole is associated with a number of important safety advantages over the current gold standard (tamoxifen) - a key consideration in early breast cancer, where otherwise "healthy" women routinely take hormonal treatment for up to 5 years after initial tumour- removing surgery. These advantages include a major reduction in the incidence of hot flushes, thromboembolic events such as deep vein thrombosis, vaginal bleeding and cancer of the womb (endometrial cancer) when compared to tamoxifen. As expected, tamoxifen was associated with a lower risk of musculo- skeletal disorders and fractures common to this age group of women compared with anastrozole.
The new results presented today come from a group of 279 ATAC trial patients(*), who, as part of an additional study, underwent annual checks during the trial to investigate specifically the effects of treatment on the endometrium. So far, 179 women have been examined at the start of the study and after 12 and 24 months of treatment. Among these patients, fewer endometrial changes were seen in the anastrozole group than the tamoxifen group (9% versus 17% respectively). Importantly, atypical hyperplasia, a potential precancerous change in the endometrium, was only observed in the tamoxifen treatment group (1.9%).
Commenting on the new data, Dr Sean Duffy, from the Division of Obstetrics and Gynaecology at St James University Hospital in Leeds, UK, and lead ATAC sub-protocol investigator said; "The small risk of developing endometrial cancer when taking tamoxifen has been a well known concern for doctors and their patients for some time. But the benefits of tamoxifen treatment in reducing the chances of breast cancer recurring in these women far outweighs this risk."
"Now, the ATAC study, which involves a vast number of women worldwide has shown anastrozole to be even more effective than tamoxifen in reducing the chance of breast cancer recurrence" he continued. "And our study results clearly show a reduced risk of endometrial changes among women taking anastrozole. Together, these findings make a compelling case for the future use of anastrozole as an alternative to tamoxifen in the treatment of postmenopausal women with early breast cancer."
Anastrozole is the only hormonal agent that has yet been proven to be superior to the "gold standard" tamoxifen in postmenopausal women with early breast cancer, and it marks an incredibly important breakthrough in the management of this devastating disease. ATAC is the largest cancer treatment trial ever conducted, involving over 9,300 post-menopausal women world-wide.
(*) "Arimidex" n equals 99, tamoxifen n equals 92, combination treatment n equals 88
"Arimidex" is a trademark, property of the AstraZeneca Group of Companies.
Notes to editors:
- Tamoxifen is an anti-oestrogen and acts primarily to prevent oestrogen binding to its receptor at tumour sites. Anastrozole is an aromatase inhibitor and acts differently to tamoxifen by blocking the production of oestrogen by the aromatase enzyme pathway - the primary source of oestrogen in postmenopausal women, whose ovaries no longer function.
- The current treatment strategy for early-stage breast cancer (cancer that has not spread beyond the breast) in postmenopausal women generally consists of surgery to remove the tumour, which may be followed by a course of chemotherapy and/or radiotherapy. Women will usually then go on to take a hormonal treatment - such as tamoxifen - for around five years to reduce the risk of the cancer recurring (this is known as "adjuvant therapy"). The patient group in the ATAC study had completed primary surgery, radiotherapy and chemotherapy (if given) before randomisation and were candidates to receive hormonal adjuvant therapy.
- The ATAC study involved investigators from 381 cancer centres in 21 countries. It started in 1996 and completed recruitment in 2000, with a total of 9366 patients participating.
- The women taking part in the ATAC study were randomised to receive treatment with anastrozole 1mg daily, tamoxifen 20mg daily, or the same two agents in combination. Treatment will be continued for five years or until recurrence of the disease, or death.
- After an average of 33 month's follow-up, 317 out of 3,125 women in the anastrozole group relapsed or died compared with 379 out of 3,116 women in the tamoxifen group and 383 out of 3,125 in the combination group.
- The combination of anastrozole plus tamoxifen in the ATAC study gave very similar results to tamoxifen on its own, and there was no additional benefit in terms of either efficacy or tolerability from giving the two in combination.
- In terms of adverse events, deep vein thrombosis was reported in almost twice as many patients taking tamoxifen compared with anastrozole patients (1.7 % vs 1.0%), endometrial cancer occurred in five times as many tamoxifen patients as those treated with anastrozole (0.5% vs less than 0.1%). Vaginal bleeding was reported in 8.1% of tamoxifen patients and 4.5 % of anastrozole patients respectively. Hot flushes were also more common among women treated with tamoxifen compared to those taking anastrozole (39.7% vs 34.3%). Fractures (predominantly of the wrist) were reported in 3.7% of tamoxifen patients and 5.8% of anastrozole patients. Joint pains were reported in 21.2% vs. 27.8% of tamoxifen and anastrozole patients, respectively.
- The objective of the endometrial sub-protocol study, which involved 279 ATAC trial patients, ("Arimidex" n equals 99, tamoxifen n equals 92 combination treatment n equals 88) was to measure the incidence of abnormal endometrial histology among a sub-population of ATAC study subjects matched for tumour characteristics and demography. These women underwent annual examination using hysteroscopy and transvaginal ultrasound during the trial. So far, 179 women have been examined at the start of the study and after 12 and 24 months' treatment.
- Anastrozole was first marketed in 1995 and is licensed for use in the first and second-line treatment of advanced breast cancer in postmenopausal women. It is currently promoted for adjuvant use in early breast cancer in Japan, however regulatory approval for use in this indication is currently being sought in other countries around the world and is expected throughout 2002.
