Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial

Coombes, R. C., Kilburn, L. S., Snowdon, C. F., Paridaens, R., Coleman, R. E., Jones, S. E., Jassem, J., Van de Velde, C. J. H., Delozier, T., Alvarez, I., Del Mastro, L., Ortmann, O., Diedrich, K., Coates, A. S., Bajetta, E., Holmberg, S. B., Dodwell, D., Mickiewicz, E., Andersen, J., Lonning, P. E., Cocconi, G., Forbes, J., Castiglione, M., Stuart, N., Stewart, A., Fallowfield, L.J, Bertelli, G., Hall, E., Bogle, R. G., Carpentieri, M., Colajori, E., Subar, M., Ireland, E. and Bliss, J. M. (2007) Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet, 369 (9561). pp. 559-570. ISSN 0140-6736

Full text not available from this repository.

Abstract

Background Early improvements in disease-free survival have been noted when an aromatase inhibitor is given either instead of or sequentially after tamoxifen in postmenopausal women with oestrogen-receptor-positive early breast cancer. However, little information exists on the long-term effects of aromatase inhibitors after treatment, and whether these early improvements lead to real gains in survival.

Methods 4724 postmenopausal patients with unilateral invasive, oestrogen-receptor-positive or oestrogen-receptor-unknown breast cancer who were disease-free on 2-3 years of tamoxifen, were randomly assigned to switch to exemestane (n=2352) or to continue tamoxifen (n=2372) for the remainder of a 5-year endocrine treatment period. The primary endpoint was disease-free survival; overall survival was a secondary endpoint. Efficacy analyses were intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN11883920.

Results After a median follow-up of 55.7 months (range 0-89.7), 809 events contributing to the analysis of disease-free survival had been reported (354 exemestane, 455 tamoxifen); unadjusted hazard ratio 0.76 (95% CI 0.66-0.88, p=0.0001) in favour of exemestane, absolute benefit 3.3% (95% CI 1.6-4.9) by end of treatment (ie, 2.5 years after randomisation). 222 deaths occurred in the exemestane group compared with 261 deaths in the tamoxifen group; unadjusted hazard ratio 0.85 (95% CI 0.71-1.02, p=0.08), 0.83 (0.69-1.00, p=0.05) when 122 patients with oestrogen-receptor-negative disease were excluded.

Conclusions Our results suggest that early improvements in disease-free survival noted in patients who switch to exemestane after 2-3 years on tamoxifen persist after treatment, and translate into a modest improvement in overall survival.

Item Type: Article
Keywords: Exemestane Randomised Controlled Trial breast cancer
Schools and Departments: Brighton and Sussex Medical School > Sussex Health Outcomes Research & Education in Cancer (SHORE-C)
Subjects: R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology Including cancer and carcinogens
R Medicine > RG Gynecology and obstetrics > RG0491 Diseases of the breast
Depositing User: Tracy Woodcock
Date Deposited: 18 Apr 2012 08:17
Last Modified: 30 Nov 2012 16:55
URI: http://sro.sussex.ac.uk/id/eprint/7002
📧 Request an update