The US Food and Drug Administration has approved anastrozole(Drug information on anastrozole) (Arimidex) for the adjuvant treatment of hormone-receptor-positive early breast cancer in postmenopausal women. The approval is based on research from the Arimidex, Tamoxifen(Drug information on tamoxifen), Alone or in Combination (ATAC) study, which involved more than 9,300 postmenopausal women in 21 countries. Anastrozole demonstrated a statistically significant improvement in recurrence-free survival compared to tamoxifen.
"When the ATAC results were first announced, we knew these were important findings that had the potential to impact how breast cancer is treated," said principal US investigator Aman Buzdar, md, The University of Texas M. D. Anderson Cancer Center, Houston. "With the approval of Arimidex in the adjuvant setting, women now have a treatment option other than tamoxifen."
The results of the ATAC trial were first presented at the San Antonio Breast Cancer Symposium in December 2001. Among the 3,125 women in the anastrozole group, 318 had a relapse of their breast cancer or died, compared with 379 of 3,116 women in the tamoxifen group (hazard ratio = 0.83; P = .01), representing a statistically significant 17% relative reduction in the risk of disease recurrence with anastrozole. The relative reduction in the risk of recurrence was 22% among women with confirmed hormone-sensitive tumors who received anastrozole (217 of 2,617 women) vs tamoxifen (272 of 2,598 women; hazard ratio = 0.78).
The safety and tolerability of both anastrozole and tamoxifen were evaluated in the ATAC trial in 3,093 patients taking tamoxifen and 3,092 patients taking anastrozole. Venous thromboembolic events (including deep-vein thrombosis) were reported in 4% (n = 120) of patients taking tamoxifen compared to 2% (n = 73) of anastrozole patients. Endometrial cancer occurred at a rate of 0.5% (n = 15) among tamoxifen patients compared to 0.1% (n = 3) among anastrozole patients. Vaginal bleeding was reported in 9% (n = 270) of tamoxifen patients and 5% (n = 147) of anastrozole patients. Hot flashes were also more common among women treated with tamoxifen compared to those taking anastrozole40% (n = 1,246) vs 35% (n = 1,082). Women taking anastrozole reported less vaginal discharge and ischemic cerebrovascular events than women taking tamoxifen (vaginal discharge: 3% [n = 94] vs 12% [n = 378]; ischemic events: 1% [n = 40] vs 2% [n = 74]).
Angina pectoris was reported more frequently in anastrozole-treated patients (1.7%, n = 52) than in tamoxifen-treated patients (1%, n = 30); the incidence of myocardial infarction was comparable. Women taking tamoxifen reported fewer musculoskeletal disorders and fractures (including fractures of the spine, hip, and wrist) compared to the women taking anastrozole. Fractures (predominantly of the wrist) were reported in 5% (n = 145) of tamoxifen recipients and 7% (n = 224) of anastrozole recipients. More patients receiving anastrozole were reported to have an elevated serum cholesterol compared to patients receiving tamoxifen (7% vs 3%).
Clinicians Advised to Discuss ATAC Results With Patients
Earlier this year, the American Society of Clinical Oncology (ASCO) issued guidelines on the use of aromatase inhibitors as adjuvant therapy for women with hormone-receptor-positive breast cancer. Overall, the panel considered the results of the ATAC trial and the extensive supporting data to be very promising, and they encouraged physicians to discuss these results with their patients.
The committee felt that it was too early to recommend a wholesale switch from standard use of tamoxifen in this setting and that physicians and patients need to reach their own conclusions after considering all the available data. The panel also stated that anastrozole is the only aromatase inhibitor for which clinical trial data in the adjuvant setting are available, and it should be considered the preferred agent if an aromatase inhibitor is used in this setting.
The National Comprehensive Cancer Network (NCCN) updated their breast cancer guidelines in February 2002 to include information derived from the ATAC trial and also recommended that these results be discussed with patients.
"The reason these guidelines are important to postmenopausal women with early breast cancer is that Arimidex gives them a new choice," said Judy Perotti, committee member and director of Patient Services at Y-ME National Breast Cancer Organization. "The guidelines will help women and their doctors work together to determine the best treatment option."