Anastrozole Continues to Outperform Tamoxifen at Each Efficacy Endpoint

HOUSTON—The nonsteroidal aromatase inhibitor anastrozole (Arimidex) continues to outperform tamoxifen in every efficacy measurement in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial, according to a recent 47-month update. Speaking for the ATAC Trialists’ Group, Aman U. Buzdar, MD, professor of medicine and deputy chairman of the Department of Breast Medical Oncology at The University of Texas M.D. Anderson Cancer Center, Houston, reported that the absolute differences between the two drugs are increasing with time.

The 5-year ATAC trial, which is being conducted at 381 centers in 21 countries, is evaluating anastrozole, tamoxifen, or a combination of the two among 9,366 postmenopausal women with invasive breast cancer. The median age of the group is 64, and 34% of the patients were node-positive at diagnosis. All had completed primary therapy (surgery with or without radiotherapy and/or chemotherapy) before entering the trial. The breakdown of hormone-receptor status in the ongoing trial is 84% positive, 8% negative, and 8% unknown.

Past and Current Updates

The previous ATAC follow-up, at a median of 33.3 months, analyzed 1,079 first events (Lancet 359:2131-2139, 2002). In that analysis, the anastrozole-alone group had a disease-free survival of 89.4% compared to 87.4% for the tamoxifen-alone group. Disease-free survival in the combination group was 87.2%, similar to that of the tamoxifen-alone group.

At a median follow-up of 47 months, 1,373 first events had occurred. Virtually no differences were found in the tamoxifen alone group and the tamoxifen plus anastrozole groups. Looking just at the monotherapy arms, 413 first events had occurred in the anastrozole (1 mg per day) group and 472 in the tamoxifen (20 mg per day) group. Events in the anastrozole group included 84 locoregional recurrences, 195 distant recurrences, 20 contralateral (invasive) cancers, and 5 contralateral ductal carcinoma in situ (DCIS). Among the tamoxifen group, there were 101 locoregional recurrences, 222 distant recurrences, 35 contralateral (invasive) cancers, and 5 contralateral DCIS. In each treatment group, 109 women died before experiencing a recurrence.

Advantage May Be Increasing

In the overall population, disease-free survival for patients in the anastrozole arm was 86.9% compared to 84.5% for those in the tamoxifen arm. The hazard ratio for disease-free survival was 0.86. When nonbreast cancer deaths were excluded, the hazard ratio improved to 0.83, or a 17% reduction in the probability of breast cancer recurrence among the anastrozole-treated patients.

Among hormone-receptor-positive patients, disease-free survival was 89% for anastrozole-treated patients vs 86.1% for those taking tamoxifen. The hazard ratio for disease-free survival was 0.82. The absolute difference in disease-free survival among this group was 2.9% at 47 months compared to 1.7% at the 33.3-month follow-up, suggesting that anastrozole’s advantage over tamoxifen is increasing over time.

In an analysis of contralateral breast cancers, anastrozole again showed superior efficacy to tamoxifen. Among the overall study population, the hazard ratio was 0.62 in favor of anastrozole. When the analysis was restricted to hormone-receptor-positive patients, the hazard ratio improved to 0.56.

In the large subgroups of receptor-positive patients, node-negative patients, and patients who did not receive chemotherapy, anastrozole had a highly favorable impact, and the differences were highly significant, according to Dr. Buzdar. Moreover, he noted that a similar trend is emerging among the approximately 20% of patients who had received chemotherapy. (Chemotherapy was not standardized.)

Recurrences Reduced Overall

"These updated analyses show that based on an intent-to-treat there is an overall 14% reduction in the risk of recurrence with anastrozole and an 18% reduction among patients with hormone-receptor-positive disease," Dr. Buzdar said. "Breast cancer recurrences were reduced by 17% overall and by 22% among ER-positive patients. The incidence of secondary breast cancer was reduced by 38% in the overall population and by 44% in hormone-receptor-positive patients."