ATAC Results Confirm Anastrozole Efficacy, Safety vs Tam

SAN ANTONIO—Anastrozole (Arimidex) is the initial treatment of choice for postmenopausal women with hormone-receptor-positive (HR+) early breast cancer, Anthony Howell, MD, University of Manchester, UK, said at the 27th Annual San Antonio Breast Cancer Symposium (abstract 1). Final results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial showed the aromatase inhibitor to have superior efficacy and a better side effect profile than tamoxifen.

ATAC was a large-scale 21-country, 381-center trial that randomized 9,366 patients to tamoxifen (n = 3,116) or anastrozole (n = 3,125) for 5 years. A combination arm was discontinued early when it was shown to offer no benefit over tamoxifen alone. Most women (84%) were HR+, and 61% were node negative. The overall group was low risk, with 64% having T1 tumors.

After a mean follow-up of 68 months, the advantage in HR+ women for anastrozole in disease-free survival was an absolute 3.3%, a 17% risk reduction (hazard ratio [HR] = 0.83, P = .005). The absolute advantage for time to recurrence in HR+ patients was 3.7% (P = .0002), a risk reduction of 26% (HR = 0.74).

The incidence of contralateral breast cancer in HR+ patients was nearly halved, Dr. Howell said (anastrozole 26 of 2,618, tamoxifen 53 of 2,598; HR = 0.47, P = .001). The incidence of invasive cancers among these patients was also significantly lower for the anastrozole group (21 vs 48 cases for tamoxifen, P = .001).

At the borderline of significance (P = .06), time to distant recurrence favored anastrozole with a 16% reduction in HR+ women. A 13% increase in time to breast cancer death in the anastrozole group was not significant (P = .2).

While particular advantages were found for HR+/node-negative and chemotherapy-naïve women, anastrozole advantages were apparent across all subgroups. For those women who were both estrogen-receptor positive and progesterone-receptor negative, the risk reduction in time to recurrence was 57% (HR = 0.43) for anastrozole at 6 years.

Overall survival was similar between groups, but differences may emerge with longer follow-up in these good-prognosis patients. Dr. Howell pointed out that in the NSABP B14 tamoxifen vs placebo trial and in the Oxford overview of tamoxifen, a breast cancer survival advantage for tamoxifen vs placebo was not found until follow-up of 7 years. He also noted that without adjuvant treatment, breast cancer recurrence rates of 38% have been reported at 5 years. That rate was cut in half with tamoxifen, and was reduced a further 26% with anastrozole in ATAC. This reduction in risk of recurrence with anastrozole suggests that the drug will also eventually reduce deaths from breast cancer.

Hysterectomy rates were 1.3% for anastrozole and 5.1% for tamoxifen (P < .001). Other significantly reduced adverse event rates with anastrozole were hot flashes, vaginal bleeding, vaginal discharge, endometrial cancer, ischemic cerebrovascular events, venous thromboembolic events, and joint symptoms.

There was an increase in fracture rates with anastrozole (11.0% vs 7.7%, P < .0001) attributed to more vertebral fractures, but not more hip or wrist fractures. Putting fracture rates in perspective, Dr. Howell reported control group rates per 1,000 woman-years of 18.4 and 19.1 from other trials, compared with the 22.6 and 15.6 rates, respectively, for anastrozole and tamoxifen.

More Patients Stay on Treatment

In summary, Dr. Howell said that anastrozole demonstrates superior efficacy to tamoxifen and is better tolerated overall. "You can treat more patients with anastrozole because of fewer adverse events, fewer serious adverse events, and fewer adverse events leading to withdrawal from treatment. More patients stay on treatment, and more patients get the benefit," he said. Furthermore, he added, the fact that benefit emerges within the first 3 years of treatment justifies offering treatment as early as possible. In answer to a question from the audience, he said that cost-benefit analyses favor anastrozole, with the higher initial cost of the drug offset by savings ensuing from lower adverse event rates, including lower hysterectomy rates.

The updated study results were recently published in The Lancet (365:60-62, 2005).