[104] A detailed analysis of the benefits of anastrozole over tamoxifen for venous thromboembolic events (VTEs) after 5 years treatment.

Cuzick J, Wale C, on Behalf of the ATAC Trialists' Group.. Wolfson Institute of Preventative Medicine, London, United Kingdom

Background: Long-term tamoxifen therapy is associated with increased risk of thromboembolic events. Aromatase inhibitors have a different mode of action and are unlikely to be associated with the same long-term risks as tamoxifen.
Materials and Methods: The Arimidex, Tamoxifen, Alone or in Combination (ATAC; ISRCTN18233230) trial compared the efficacy and safety of 5 years anastrozole, tamoxifen or the combination as adjuvant therapy for 9366 postmenopausal women with early invasive breast cancer. The combination was discontinued due to no efficacy benefit, but these patients were still followed up. The incidence of VTE during treatment (prior to recurrence) or 14 days after discontinuation was determined for each group. Risk factors associated with VTE were also examined.
Results: At 68 months median follow-up, 382 women had 1 VTE. Considering the most serious event per patient, there were 51 pulmonary emboli, 147 deep vein thromboses, 6 retinal vein thromboses and 178 cases of superficial thrombophlebitis. Rates were similar in the tamoxifen/combination groups (odds ratio [OR] 1.10 [95%CI 0.88-1.40]; p=0.38), but were 39% lower for anastrozole compared with tamoxifen (OR 0.61 [95%CI 0.46-0.80]; p<0.0001). In the tamoxifen/combination groups, risk of VTE was highest early on in treatment but remained elevated throughout the 5-yr period. Age was a strong risk factor for VTE (Chi square value 30.6) with the OR increasing by 3.2%/yr for age at randomization. Body mass index was also predictive of VTE (Chi square value 30.1) with a 5.2% increase in risk per unit change. After stratifying for age and time on treatment, neither smoking status (OR 0.82) nor prior hormone replacement therapy (OR 0.92) were significantly associated with risk, although both are risk factors for VTE. Prior use of chemotherapy (OR 1.02) or radiotherapy (OR 1.10) did not affect risk. Risk was similar if superficial thrombophlebitis was excluded. The strongest single risk factor for VTE was immobility (due to major surgery, fracture, or infection in the preceding 90 days) in the previous 6 months (OR 4.62 [95%CI: 3.12-6.78]; p<0.0001). Immobility occurred prior to VTE in 57 cases (14.9%). When superficial thrombophlebitis was excluded the risk associated with immobility was even higher (OR 6.13 [95%CI 3.69-10.2]) and was similar between treatment groups. Adjusting for risk factors did not materially change the risk associated with each treatment.
Discussion: Anastrozole was associated with a substantially lower risk of VTE than tamoxifen/combination treatment groups, in all prognostic groups examined. Risk was greatest in the initial treatment period but persisted over the 5 yrs. Increasing age or immobility in the previous 6 months were the strongest risk factors for VTE and appeared independent of treatment. This difference in risk represents a major long-term safety benefit for anastrozole compared with tamoxifen in the adjuvant treatment of early breast cancer.

Thursday, December 14, 2006 5:00 PM

Poster Discussion Session I: Aromatase Inhibitors (5:00 PM-7:00 PM)