Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial
Coombes R., Kilburn L., Snowdon C., Paridaens R., Coleman R., Jones S., Jassem J., Van de Velde C., Delozier T., Alvarez I., Del Mastro L., Ortmann O., Diedrich K., Coates A., Bajetta E., Holmberg S., Dodwell D., Mickiewicz E., Andersen J., Lønning P., Cocconi G., Forbes J., Castiglione M., Stuart N., Stewart A., Fallowfield L., Bertelli G., Hall E., Bogle R., Carpentieri M., Colajori E., Subar M., Ireland E., Bliss J.
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. © 2007 Elsevier Ltd. All rights reserved.