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.