Early-Stage Breast Cancer Responds to Aromatase Inhibitor Therapy

SAN ANTONIO, Dec. 18 -- If a big study of the post-tamoxifen use of Aromasin (exemestane) for early breast caner had gone to its conclusion, the aromatase inhibitor would have fared as well as Femara (letrozole), a competitor, an investigator said here.

Post-menopausal women with early stage breast cancer who have finished five years of tamoxifen "now have another option in terms of another aromatase inhibitor," asserted Terry Mamounas, M.D., of Northeastern Ohio Universities College of Medicine in Canton.

The finding emerged from a large randomized controlled trial - the National Surgical Adjuvant Breast and Bowel Project B-33 study - that was halted prematurely in October 2003, Dr. Mamounas told the San Antonio Breast Cancer Symposium.

The study was stopped with 1,598 patients enrolled -- about half of the planned 3,000 -- because another trial, studying Femara (letrozole) against placebo, showed a dramatic benefit for that drug, Dr. Mamounas said.

Women in the NSABP B-33 study were allowed to continue getting Aromasin if they had been in the active arm and placebo patients were offered the opportunity to cross over to the drug, he said.

Volunteers were followed of a median of 30 months, Dr. Mamounas said, and an intent-to-treat analysis showed:

• 72% of Aromasin patients stayed on the drug, while 44% of placebo patients switched.
• Disease-free survival was 91% for Aromasin versus 89% for placebo, but the difference was not statistically significant.
• On the other hand, the Aromasin arm had a 56% reduction in relapses, compared with placebo, which was statistically significant at P=0.004.
• There was no difference in overall survival.
• Toxicity (assessed up to the time of unblinding) was higher in the Aromasin arm - including 9% versus 6% Grade 3 events, a difference that was significant at P=0.03.

"Despite the crossover," Dr. Mamounas said, "we saw a 56% reduction in relapses which might indicate that the effect might have been even larger if the study had been left untouched."

"Exemestane is probably as effective as the other two drugs (Femara and Arimidex [anastrozole]) in this particular setting," he said.

Although the trial was stopped early, it "mirrors" the result of the Femara trial, according to William Gradishar, M.D., of Northwestern University in Chicago, who has studied Aromasin in other patient populations.

The value of the results, he said, "is still limited by the number of patients who were available but my guess is that if (the trial) had gone through, you would have seen similar things" as were found in the Femara study.

Doctors "tend to think of most of these drugs, quite frankly, as fairly interchangeable," he said, and the data from Dr. Mamounas will confirm that view.

Dr. Mamounas said he's on the speakers' bureau and is a consultant for Pfizer, which makes Aromasin, as well as AstraZeneca, which makes Arimidex, and Novartis, which makes Femara. Dr. Gradishar said he had no relevant financial conflicts.