Exemestane may improve survival after tamoxifen therapy

April 30, 2008

NEW YORK (Reuters Health) - In women with early-stage, hormone receptor-positive breast cancer, extended therapy with the steroidal aromatase inhibitor exemestane after 5 years of treatment with tamoxifen significantly improves relapse-free survival, according to an analysis of the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-33 trial.

Exemestane therapy was not, however, associated with a statistically significant improvement in disease-free survival, the study's primary endpoint, the results indicate.

"These findings demonstrate that exemestane may provide another option for the extended adjuvant treatment of postmenopausal women with hormone-receptor-positive breast cancer who complete 5 years of adjuvant tamoxifen," Dr. Eleftherios P. Mamounas and colleagues conclude.

The study, which is reported in the Journal of Clinical Oncology for April 20, involved 1598 postmenopausal patients who were disease-free after tamoxifen therapy and were randomized to receive exemestane (25 mg/day) or placebo for 5 years.

When B-33 began, there was little information regarding the benefits of aromatase inhibitors following tamoxifen therapy. While patient accrual was occurring, however, the results of a similarly designed Canadian study suggested that aromatase inhibitor therapy was, in fact, beneficial in this setting. This led the NSABP monitoring committee to recommend terminating B-33 accrual, unblinding treatment assignment, and offering exemestane to patients in the placebo group.

Overall, 72% of patients randomized to receive exemestane continued with the drug and 44% of those in the placebo group elected to switch to the drug, Dr. Mamounas, from the Aultman Health Foundation in Canton, Ohio, and colleagues note.

During a median follow-up period of 30 months, original exemestane assignment was associated with higher 4-year disease-free survival than with placebo: 91% vs. 89%. However, the difference fell short of statistical significance.

By contrast, the 96% relapse-free survival seen with exemestane therapy was significantly better than the 94% noted with placebo (p = 0.004).

Treatment with the agent was generally well tolerated and associated with acceptable toxicity.

"Despite early closure of accrual and considerable crossover to exemestane, original exemestane assignment in our trial resulted in reductions in disease-free survival and relapse-free survival events of a magnitude similar to those seen with nonsteroidal aromatase inhibitors in the same setting," the investigators state.