Placebo-Controlled Study to Evaluate Adjuvant Exemestane After Tamoxifen

CANTON,Ohio—Occult micrometastases may still be present after the standard 5 years of tamoxifen adjuvant hormonal treatment for patients with stage I or II breast cancer and receptor-positive tumors. Some of those micrometastases may be estrogen- or tamoxifen-sensitive, stated Terry Mamounas, MD, adding that this is a major reason the National Surgical Adjuvant Breast and Bowel Project (NSABP) has undertaken clinical trial NSABP B-33. The trial will compare 2 years of exemestane (Aromasin) to 2 years of placebo in postmenopausal, estrogen receptor-positive stage I-II breast cancer patients who are disease free after being on tamoxifen (Nolvadex) for 5 years.

Dr. Mamounas, Medical Director at Aultman Cancer Center in Canton, Ohio, discussed the B-33 trial design (see Figure) at a clinical investigators’ workshop sponsored by the University of Texas M. D. Anderson Cancer Center and Pharmacia Oncology.

Study Aims and Design

“The primary aim of this study is to determine whether adjuvant exemestane after 5 years of tamoxifen prolongs disease-free survival vs placebo,” Dr. Mamounas said. “Secondary aims are to determine whether adjuvant exemestane prolongs overall survival vs placebo and to evaluate the effect of exemestane and of tamoxifen withdrawal on bone mineral density.”

The protocol design calls for enrollment of 3,000 patients, which is anticipated to require 40 months. The study is designed to have an 80% power to detect a 21% reduction in hazard rate and assumes that 50% of patients will be node-negative.