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 T(1-3)N(1)M(0) breast cancer who were disease free after 5 years oftamoxifen 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 theexemestane 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.
RCT Entities:
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 T(1-3)N(1)M(0) 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.
Authors: Peter Blaha; Ruth Exner; Andrea Dal Borgo; Sinda Bigenzahn; Peter Panhofer; Otto Riedl; Sebastian Schoppmann; Thomas Bachleitner-Hofmann; Emanuel Sporn; Ursula Pluschnig; Florian Fitzal; Guenther Steger; Raimund Jakesz; Peter Dubsky; Michael Gnant Journal: Breast Care (Basel) Date: 2009-06-23 Impact factor: 2.860
Authors: Eleftherios P Mamounas; Hanna Bandos; Barry C Lembersky; Jong-Hyeon Jeong; Charles E Geyer; Priya Rastogi; Louis Fehrenbacher; Mark L Graham; Stephen K Chia; Adam M Brufsky; Janice M Walshe; Gamini S Soori; Shaker R Dakhil; Thomas E Seay; James L Wade; Edward C McCarron; Soonmyung Paik; Sandra M Swain; D Lawrence Wickerham; Norman Wolmark Journal: Lancet Oncol Date: 2018-11-30 Impact factor: 41.316
Authors: James N Ingle; Daniel J Schaid; Paul E Goss; Mohan Liu; Taisei Mushiroda; Judy-Anne W Chapman; Michiaki Kubo; Gregory D Jenkins; Anthony Batzler; Lois Shepherd; Joseph Pater; Liewei Wang; Matthew J Ellis; Vered Stearns; Daniel C Rohrer; Matthew P Goetz; Kathleen I Pritchard; David A Flockhart; Yusuke Nakamura; Richard M Weinshilboum Journal: J Clin Oncol Date: 2010-09-27 Impact factor: 44.544
Authors: Meredith M Regan; Patrick Neven; Anita Giobbie-Hurder; Aron Goldhirsch; Bent Ejlertsen; Louis Mauriac; John F Forbes; Ian Smith; István Láng; Andrew Wardley; Manuela Rabaglio; Karen N Price; Richard D Gelber; Alan S Coates; Beat Thürlimann Journal: Lancet Oncol Date: 2011-10-20 Impact factor: 41.316