EXEMESTANE AS EFFECTIVE AS ANASTRAZOLE 

J Clin Oncol. 2013 Feb 4. [Epub ahead of print]

Exemestane Versus Anastrozole in Postmenopausal Women With Early Breast Cancer: NCIC CTG MA.27--A Randomized Controlled Phase III Trial.

Goss PE, Ingle JN, Pritchard KI, Ellis MJ, Sledge GW, Budd GT, Rabaglio M, Ansari RH, Johnson DB, Tozer R, D'Souza DP, Chalchal H, Spadafora S, Stearns V, Perez EA, Liedke PE, Lang I, Elliott C, Gelmon KA, Chapman JA, Shepherd LE.

Source

Paul E. Goss and Pedro E.R. Liedke, Massachusetts General Hospital, Boston, MA; James N. Ingle, Mayo Clinic, Rochester, MN; Matthew J. Ellis, Siteman Cancer Center, Washington University, St Louis, MO; George W. Sledge, Indiana University Health, Indianapolis; Rafat H. Ansari, Northern Indiana Cancer Research Consortium, South Bend, IN; G. Thomas Budd, Cleveland Clinic, Cleveland, OH; David B. Johnson, Cancer Center of Kansas, Wichita, KS; Vered Stearns, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD; Edith A. Perez, Mayo Clinic, Jacksonville, FL; Kathleen I. Pritchard, Sunnybrook Odette Cancer Centre; University of Toronto, Toronto; Richard Tozer, Juravinski Cancer Centre, Hamilton; David P. D'Souza, London Regional Cancer Program, London; Silvana Spadafora, Algoma Regional Cancer Centre, Sault St Marie; Catherine Elliott, Judy-Anne W. Chapman, and Lois E. Shepherd, NCIC Clinical Trials Group, Kingston, Ontario; Haji Chalchal, Regina General Hospital, Regina, Saskatchewan; Karen A. Gelmon, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Manuela Rabaglio, International Breast Cancer Study Group Coordinating Center and Inselspital, Bern, Switzerland; Istvan Lang, National Institute of Oncology, Budapest, Hungary.

Abstract

PURPOSEIn patients with hormone-dependent postmenopausal breast cancer, standard adjuvant therapy involves 5 years of the nonsteroidal aromatase inhibitors anastrozole and letrozole. The steroidal inhibitor exemestane is partially non-cross-resistant with nonsteroidal aromatase inhibitors and is a mild androgen and could prove superior to anastrozole regarding efficacy and toxicity, specifically with less bone loss. PATIENTS AND METHODSWe designed an open-label, randomized, phase III trial of 5 years of exemestane versus anastrozole with a two-sided test of superiority to detect a 2.4% improvement with exemestane in 5-year event-free survival (EFS). Secondary objectives included assessment of overall survival, distant disease-free survival, incidence of contralateral new primary breast cancer, and safety.ResultsIn the study, 7,576 women (median age, 64.1 years) were enrolled. At median follow-up of 4.1 years, 4-year EFS was 91% for exemestane and 91.2% for anastrozole (stratified hazard ratio, 1.02; 95% CI, 0.87 to 1.18; P = .85). Overall, distant disease-free survival and disease-specific survival were also similar. In all, 31.6% of patients discontinued treatment as a result of adverse effects, concomitant disease, or study refusal. Osteoporosis/osteopenia, hypertriglyceridemia, vaginal bleeding, and hypercholesterolemia were less frequent on exemestane, whereas mild liver function abnormalities and rare episodes of atrial fibrillation were less frequent on anastrozole. Vasomotor and musculoskeletal symptoms were similar between arms. CONCLUSIONThis first comparison of steroidal and nonsteroidal classes of aromatase inhibitors showed neither to be superior in terms of breast cancer outcomes as 5-year initial adjuvant therapy for postmenopausal breast cancer by two-way test. Less toxicity on bone is compatible with one hypothesis behind MA.27 but requires confirmation. Exemestane should be considered another option as up-front adjuvant therapy for postmenopausal hormone receptor-positive breast cancer.