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Exemestane After Tamoxifen May Improve Disease-Free Survival for Postmenopausal Women with Primary Breast Cancer Over Tamoxifen Alone

Postmenopausal women who are recurrence-free after 2 to 3 years of tamoxifen therapy for primary breast cancer show significantly improved disease-free survival after switching to exemestane therapy compared with those who continue with the standard 5-year tamoxifen regimen, according to interim results of a phase 3 trial.

"We found that switching patients to adjuvant treatment with exemestane after 2 to 3 years of tamoxifen therapy was associated with a statistically and clinically significant improvement in disease-free survival, which included a reduction in the incidence of metastatic disease," reports R. Charles Coombes, MD, PhD, Imperial College, London, United Kingdom, and colleagues for the Intergroup Exemestane Study.

Overall, 2,362 women were randomised to receive 25 mg oral exemestane daily while 2,380 women received 20 mg tamoxifen daily to complete a total of 5 years of adjuvant endocrine treatment after remaining disease-free with 2 to 3 years of tamoxifen therapy. Baseline characteristics were balanced between groups and the median follow up was 30.6 months for a primary endpoint of disease-free survival. Analyses are on the intention-to-treat basis.

The exemestane group experienced 183 first events compared with 266 in the tamoxifen group, which represents a 32% reduction in risk and corresponds to an absolute benefit of 4.7% in disease-free survival. Three years after randomisation, disease-free survival was 91.5% in the exemestane group and 86.8% in the tamoxifen group.

In a subsidiary analysis of breast-cancer-free survival, which excluded deaths in patients who did not have a recurrence or contralateral breast cancer, the exemestane group had 144 events compared with 227 in the tamoxifen group. Contralateral breast cancer occurred in 9 and 20 patients, respectively, in the exemestane and tamoxifen groups.

As of this second interim analysis, the investigators note no statistically significant difference in overall survival, reporting 93 and 106 deaths in the exemestane and tamoxifen groups, respectively.

The exemestane group experienced a higher incidence of arthralgia, diarrhoea, osteoporosis, and visual disturbances; while the tamoxifen group was more likely to have gynaecologic symptoms, vaginal bleeding, muscle cramps, and thromboembolic events. The tamoxifen group also had higher rates of a second primary non-breast cancer that occurred before a distant relapse, than did patients treated with exemestane.

"Our results add to the evidence that the sequential use of aromatase inactivators and tamoxifen provides additional options for improving adjuvant endocrine therapy for postmenopausal women with hormone-responsive primary breast cancer," the authors conclude, adding "our results indicate that five years of tamoxifen monotherapy after surgery may be suboptimal for postmenopausal patients with estrogen-receptor-positive breast cancer."

N Engl J Med 2004;350:1081-92.

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