Breast cancer drug “surpasses” tamoxifenBMJ 2001; 323 doi: https://doi.org/10.1136/bmj.323.7326.1387a (Published 15 December 2001) Cite this as: BMJ 2001;323:1387
The British pharmaceutical company AstraZeneca claimed this week that “the established benefits of tamoxifen in early breast cancer have been surpassed by another treatment.”
Dr Jeffrey Tobias, consultant radiotherapist and oncologist at University College London Hospitals, who presented early results of a five year trial of the drug to the press this week, predicted that anastrozole (Aridex) would “knock tamoxifen off its poll position over the next 15 years.”
Data came from the ATAC (Aridex, tamoxifen alone or in combination) randomised trial of 9366 postmenopausal women with operable breast cancer. Recruitment took place in 21 countries, with over 3000 patients coming from the United Kingdom. Between 1996 and 2000, women who had completed surgery were randomised into one of three arms to compare tamoxifen, anastrozole, or a combination of both drugs.
Thirty three months into the five year trial, a retrospective subgroup analysis has shown that anastrozole is significantly more effective than tamoxifen at increasing the disease free survival time. A total of 317 of 3125 women in the anastrozole arm of the study had a relapse in their breast cancer or died, compared with 379 of the 3116 women in the tamoxifen arm.
Figures for women with confirmed oestrogen sensitive tumours showed an even greater benefit from anastrozole, with a 22% reduction in risk of recurrence of breast cancer. Additionally, whereas tamoxifen reduces contralateral recurrence by 50%, anastrozole improves this figure by a further 50%.
Patients who took both drugs, however, did no better than the tamoxifen alone group. Dr Tobias said the reasons for this were “not certain.” However, the effect could be due to the partial agonist effect of tamoxifen on breast tissue once oestrogen levels had been reduced to a low level by anastrozole.
Dr Tobias explained that the researchers had analysed their results at 33 months, because it was in the trial protocol to do a preliminary analysis once 1,000 events had occurred. This happened sooner than expected.
The results are expected to be published in the next six months. “It is a triumph for British medicine,” Dr Tobias said.
Previous studies have been inconsistent in showing the superiority of aromatase inhibitors, the group of drugs to which anastrozole belongs (20 October, p 880). One large study suggested that anastrozole was superior to tamoxifen, and another showed that its efficacy was similar to tamoxifen's.
Anastrozole, a third generation aromatase inhibitor, works by blocking the action of the enzyme aromatase. Aromatase is found in the fatty tissues of postmenopausal women, where it is responsible for the final step in oestrogen production, the conversion of androgens to oestrogen. If the production of oestrogen is blocked, the growth of oestrogen sensitive breast tumours is slowed down or stopped. Tamoxifen has a different mode of action. It works by blocking the oestrogen receptors found on oestrogen sensitive tumours, thereby preventing circulating oestrogen from stimulating cell growth.
Dr Tobias said that figures released on adverse events also show that anastrozole is better tolerated on most indices compared with tamoxifen. Endometrial cancers occurred in 1.0% of women taking tamoxifen compared with 0.5% of women taking anastrozole. Deep vein thrombosis, weight gain, and vaginal bleeding were also less common in the anastrozole group.
However, fracture rates and musculoskeletal disorders were higher in the anastrozole arm and likely to be due to lower levels of circulating oestrogen. Almost 6% of women taking anastrozole had fractures compared with 3.7% who took tamoxifen. Twenty seven per cent of women taking anastrozole complained of musculoskeletal compared with 21.2% of those taking tamoxifen. Dr Tobias said that these adverse effects were “offset by the benefits of anastrozole.”
The principal investigator, Professor Michael Baum from University College Hospital, London, presented the results of the trial at the San Antonio Breast Cancer Meeting in the United States. He said: “These early findings show Arimidex [as anastrozole is marketed in the United States] to be an effective and well tolerated endocrine option for the treatment of postmenopausal women with early breast cancer. Longer follow up and long term data on bone mineral density and cognitive function are required to allow a complete benefit risk assessment to be made.”