100-Month Update Shows Continued Benefit for Anastrozole Over Tamoxifen

A median follow-up of 100 months has shown continued benefit for anastrozole (Arimidex) as compared with tamoxifen in a study of postmenopausal women with hormone receptor-positive tumors.

John F. Forbes, MD
Photo Courtesy SABCS/Todd Buchanan 2007

Data from the ATAC (Arimidex, Tamoxifen, Alone or in Combination) study show that the effects of anastrozole in decreasing the risk of recurrence continue even after patients have completed therapy, according to John F. Forbes, MD, Professor of Surgical Oncology, University of Newcastle, and Director of Surgical Oncology, Calvary Mater Newcastle Hospital, New South Wales, Australia. The study evaluated 5 years of primary adjuvant therapy with an aromatase inhibitor or tamoxifen in 6241 postmenopausal women. At median follow-up times of 33 and 68 months, anastrozole was more effective, had fewer serious side effects, and was better tolerated than tamoxifen during active treatment. The question remained whether efficacy benefits or side effects would persist after treatment completion. This question was answered in the update presented by Dr. Forbes, which was based on data collected at 100 months, or approximately 9 years, some 3 or more years after patients had completed their treatment. This amounts to 46,292 patient-years of data. At 9 years, anastrozole demonstrated a significant advantage in terms of disease-free survival, time to recurrence, time to distant recurrence, and incidence of new contralateral breast cancers. Furthermore, side effects associated with the drug had diminished.

Dr. Forbes reported hazard ratios favoring anastrazole over tamoxifen:

• disease-free survival, 0.85 (P = .003)
• time to recurrence, 0.76 (P = .0001)
• time to distant recurrence, 0.84 (P = .022)
• contralateral breast cancer, 0.60 (P = .004)

Deaths after recurrence were the same at 11% to 12%, as were deaths from all causes, at 20% per arm.

The difference in recurrences has become even greater, Dr. Forbes said. Recurrence rates at 5 years were 12.5% on tamoxifen and 9.7% on anastrozole, for a 2.8% absolute reduction. At 9 years, they were 21.8% versus 17.0%, for a 4.8% absolute reduction. "This is the first demonstration of a carry-over effect with an aromatase inhibitor, and it is significantly larger for anastrazole than tamoxifen," he said. "The significant result of this is a 25% ongoing reduction in breast cancer events with anastrazole over tamoxifen." He added that with longer follow-up, the differences have also widened in time to distance recurrence and in incidence of contralateral breast cancer. Contralateral breast cancers developed in 4.2% on tamoxifen and 2.5% on anastrazole. "It is plausible that aromatase inhibitors, in this case anastrozole, could have a substantial effect in preventing breast cancer," Dr. Forbes said. The side effect profile at 9 years has also shifted since the previous analysis. "The fracture rate has almost disappeared," he said. While the annual rate of fractures was approximately 50% higher with anastrazole during active treatment, they became similar with longer follow-up, based on fractures in approximately 145 patients per arm. Endometrial cancers also occurred less often with anastrazole off-treatment, in 4 patients versus 12 on tamoxifen. "It is clear that at 100 months, anastrozole is significantly superior to tamoxifen in preventing breast cancer recurrences, and the absolute difference between the agents continues to increase after treatment is completed," Dr. Forbes said.

Disclosures:

The author(s) have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.