Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): a randomised phase 3 trial

Velde, C.J.H. van de; Rea, D.; Seynaeve, C.; Putter, H.; Hasenburg, A.; Vannetzel, J.M.; ... ; Jones, S.E. (2011)

Article / Letter to editor

BACKGROUND Aromatase inhibitors improved disease-free survival compared with tamoxifen when given as an initial adjuvant treatment or after 2-3 years of tamoxifen to postmenopausal women with hormone-receptor-positive breast cancer. We therefore compared the long-term effects of exemestane monotherapy with sequential treatment (tamoxifen followed by exemestane). METHODS The Tamoxifen Exemestane Adjuvant Multinational (TEAM) phase 3 trial was conducted in hospitals in nine countries. Postmenopausal women (median age 64 years, range 35-96) with hormone-receptor-positive breast cancer were randomly assigned in a 1:1 ratio to open-label exemestane (25 mg once a day, orally) alone or following tamoxifen (20 mg once a day, orally) for 5 years. Randomisation was by use of a computer-generated random permuted block method. The primary endpoint was disease-free survival (DFS) at 5 years. Main analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, NCT00279448, NCT00032136, and NCT00036270; NTR 267; Ethics Commission Trial27/2001; and UMIN, C000000057. FINDINGS 9779 patients were assigned to sequential treatment (n=4875) or exemestane alone (n=4904), and 4868 and 4898 were analysed by intention to treat, respectively. 4154 (85%) patients in the sequential group and 4186 (86%) in the exemestane alone group were disease free at 5 years (hazard ratio 0·97, 95% CI 0·88-1·08; p=0·60). In the safety analysis, sequential treatment was associated with a higher incidence of gynaecological symptoms (942 [20%] of 4814 vs 523 [11%] of 4852), venous thrombosis (99 [2%] vs 47 [1%]), and endometrial abnormalities (191 [4%] vs 19 [<1%]) than was exemestane alone. Musculoskeletal adverse events (2448 [50%] vs 2133 [44%]), hypertension (303 [6%] vs 219 [5%]), and hyperlipidaemia (230 [5%] vs 136 [3%]) were reported more frequently with exemestane alone. INTERPRETATION Treatment regimens of exemestane alone or after tamoxifen might be judged to be appropriate options for postmenopausal women with hormone-receptor-positive early breast cancer. FUNDING Pfizer.

• All authors: Velde, C.J.H. van de; Rea, D.; Seynaeve, C.; Putter, H.; Hasenburg, A.; Vannetzel, J.M.; Paridaens, R.; Markopoulos, C.; Hozumi, Y.; Hille, E.T.M.; Kieback, D.G.; Asmar, L.; Smeets, J.; Nortier, J.W.R.; Hadji, P.; Bartlett, J.M.S.; Jones, S.E.
• Date: 2011-01-22
• Volume: 377
• Issue: 9762
• Pages: 321 - 31
• DOI: doi:10.1016/S0140-6736(10)62312-4