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

• Published in: The Lancet (British edition) Vol. 377; no. 9762; pp. 321 - 331
• Main Authors: van de Velde, Cornelis JH, Prof, Rea, Daniel, MD, Seynaeve, Caroline, MD, Putter, Hein, Prof, Hasenburg, Annette, Prof, Vannetzel, Jean-Michel, MD, Paridaens, Robert, Prof, Markopoulos, Christos, Prof, Hozumi, Yasuo, MD, Hille, Elysee TM, PhD, Kieback, Dirk G, MD, Asmar, Lina, PhD, Smeets, Jan, BSc, Nortier, Johan WR, Prof, Hadji, Peyman, Prof, Bartlett, John MS, PhD, Jones, Stephen E, MD
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 22.01.2011; Elsevier; Elsevier Limited
• Subjects: Adenocarcinoma - metabolism; Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adenocarcinoma - therapy; Adult; Aged; Aged, 80 and over; Androstadienes - therapeutic use; Antineoplastic Agents, Hormonal - therapeutic use; Biological and medical sciences; Breast cancer; breast neoplasms; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Cancer; Cancer therapies; Clinical medicine; Data collection; Disease; Disease-Free Survival; Early Diagnosis; endometrium; Ethics; Family medical history; Female; General aspects; Gynecology. Andrology. Obstetrics; Hospitals; Humans; hyperlipidemia; Hypertension; Internal Medicine; long term effects; Mammary gland diseases; Mammography; Medical sciences; Meetings; Middle Aged; musculoskeletal system; patients; post-menopause; Postmenopause; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; safety assessment; Side effects; survival; tamoxifen; Tamoxifen - therapeutic use; Thromboembolism; thrombosis; Tumors; unspecific monooxygenase; women; Womens health; Steroid; Antineoplastic agent; Phase III trial; Breast disease; Antiestrogen; Adjuvant treatment; Antihormone; Estrogen synthase; Randomization; Selective estrogen receptor modulator; Clinical trial; Mammary gland; Non steroid compound; Aromatase inhibitor; Enzyme; Enzyme inhibitor; Breast cancer; Malignant tumor; Exemestane; Androstane derivatives; Tamoxifene; Medicine; Mammary gland diseases; Early; Cancer
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(10)62312-4

Summary 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 Trial 27/2001 ; 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.