JCO Early Release, published online ahead of print Mar 10 2008
Journal of Clinical Oncology, 10.1200/JCO.2007.14.0228
Received August 15, 2007
Accepted October 1, 2007
Benefit From Exemestane As Extended Adjuvant Therapy After 5 Years of Adjuvant Tamoxifen: Intention-to-Treat.Analysis of the National Surgical Adjuvant Breast and Bowel Project B-33 Trial
Eleftherios P. Mamounas,* Jong-Hyeon Jeong, D. Lawrence Wickerham, Roy E. Smith, Patricia A. Ganz, Stephanie R. Land, Andrea Eisen, Louis Fehrenbacher, William B. Farrar, James N. Atkins, Eduardo R. Pajon, Victor G. Vogel, Joan F. Kroener, Laura F. Hutchins, André Robidoux, James L. Hoehn, James N. Ingle, Charles E. Geyer Jr, Joseph P. Costantino, and Norman Wolmark
From the National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh; Allegheny General Hospital; Shadyside Hospital, University of Pittsburgh; University of Pittsburgh Cancer Institute, Magee-Womens Hospital, Pittsburgh, PA; Aultman Health Foundation, Canton, OH; University of California at Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles; Scripps Clinic, San Diego; Kaiser Permanente Northern California, Vallejo, CA; Ohio State University, Columbus, OH; CCOP Southeast Cancer Control Consortium, Winston-Salem, NC; CCOP Colorado Cancer Research Program, Denver, CO; Arkansas Cancer Research Center, Little Rock, AK; Toronto Sunnybrook Regional Cancer Center, North York, Ontario; Centre Hospitalier de l'Université de Montréal, Québec, Canada; CCOP Marshfield Clinic, Marshfield, WI; and the Mayo Clinic, Rochester, MN.
* To whom correspondence should be addressed. E-mail: tmamounas{at}aultman.com
Purpose: Patients with early-stage, hormone receptor-positive breast cancer have considerable residual risk for recurrence after completing 5 years of adjuvant tamoxifen. In May 2001, the National Surgical Adjuvant Breast and Bowel Project (NSABP) initiated accrual to a randomized, placebo-controlled, double-blind clinical trial to evaluate the steroidal aromatase inhibitor exemestane as extended adjuvant therapy in this setting.
Patients and Methods: Postmenopausal patients with clinical T1-3N1M0 breast cancer who were disease free after 5 years of tamoxifen were randomly assigned to 5 years of exemestane (25 mg/d orally) or 5 years of placebo. Our primary aim was to test whether exemestane prolongs disease-free survival (DFS). In October 2003, results of National Cancer Institute of Canada (NCIC) MA.17 showing benefit from adjuvant letrozole in this setting necessitated termination of accrual to B-33, unblinding, and offering of exemestane to patients in the placebo group.
Results: At the time of unblinding, 1,598 patients had been randomly assigned; 72% in the exemestane group continued on exemestane and 44% in the placebo group elected to receive exemestane. With 30 months of median follow-up, original exemestane assignment resulted in a borderline statistically significant improvement in 4-year DFS (91% v 89%; relative risk [RR] = 0.68; P = .07) and in a statistically significant improvement in 4-year relapse-free survival (RFS; 96% v 94%; RR = 0.44; P = .004). Toxicity, assessed up to time of unblinding, was acceptable for the adjuvant setting.
Conclusion: Despite premature closure and crossover to exemestane by a substantial proportion of patients, original exemestane assignment resulted in non-statistically significant improvement in DFS and in statistically significant improvement in RFS.
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