BIG 1-98 "COOKING" STATISTICS

J Clin Oncol. 2011 Feb 14. [Epub ahead of print] Analyses Adjusting for Selective Crossover Show Improved Overall Survival With Adjuvant Letrozole Compared With Tamoxifen in the BIG 1-98 Study. Colleoni M, Giobbie-Hurder A, Regan MM, Thürlimann B, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Láng I, Smith I, Chirgwin J, Pienkowski T, Wardley A, Price KN, Gelber RD, Coates AS, Goldhirsch A. European Institute of Oncology, Milan, Italy; Swiss Group for Clinical Cancer Research Statistical Center, Dana-Farber Cancer Institute; Harvard School of Public Health; Frontier Science and Technology Research Foundation; Harvard Medical School, Boston, MA; International Breast Cancer Study Group, Breast Center, Kantonsspital, St Gallen; International Breast Cancer Study Group, Bern; Oncology Institute of Southern Switzerland, Bellinzona, Switzerland; Danish Breast Cancer Cooperative Group, Rigshospitalet, Copenhagen, Denmark; French Breast Cancer Group, Institut Bergonié, Bordeaux, France; University of Newcastle, Calvary Mater Hospital, Australian New Zealand Breast Cancer Trials Group, Newcastle, New South Wales; Box Hill and Maroondah Hospitals, Melbourne; University of Sydney, Australia; University Hospital Gasthuisberg, Catholic University of Leuven, Belgium; National Institute of Oncology, Budapest, Hungary; The Royal Marsden Hospital; Institute of Cancer Research, London; Christie Hospital National Health Service Trust, South Manchester University Hospital Trust, Manchester, United Kingdom; and Cancer Center Maria Sklodowska-Curie Memorial Institute of Oncology, Warsaw, Poland. Abstract PURPOSE Among postmenopausal women with endocrine-responsive breast cancer, the aromatase inhibitor letrozole, when compared with tamoxifen, has been shown to significantly improve disease-free survival (DFS) and time to distant recurrence (TDR). We investigated whether letrozole monotherapy prolonged overall survival (OS) compared with tamoxifen monotherapy. PATIENTS AND METHODS Of 8,010 postmenopausal women with hormone receptor-positive, early breast cancer enrolled on the Breast International Group (BIG) 1-98 study, 4,922 were randomly assigned to 5 years of continuous adjuvant therapy with either letrozole or tamoxifen. Of 2,459 patients enrolled in the tamoxifen treatment arm, 619 (25.2%) selectively crossed over to either adjuvant or extended letrozole after initial trial results were presented in January 2005. To gain better estimates of relative treatment effects in the presence of selective crossover, we used inverse probability of censoring weighted (IPCW) modeling. Results Weighted Cox models, by using IPCW, estimated a statistically significant, 18% reduction in the hazard of an OS event with letrozole treatment (hazard ratio [HR], 0.82; 95% CI, 0.70 to 0.95). Estimates of 5-year OS on the basis of IPCW were 91.8% and 90.4% for letrozole and tamoxifen, respectively. The HRs of DFS and TDR events by using IPCW modeling were 0.83 (95% CI, 0.74 to 0.94) and 0.80 (95% CI, 0.67 to 0.94), respectively (P < .05 for DFS, OS, and TDR). Median follow-up was 74 months. CONCLUSION Adjuvant treatment with letrozole, compared with tamoxifen, significantly reduces the risk of death, the risk of recurrent disease, and the risk of recurrence at distant sites in postmenopausal women with hormone receptor-positive breast cancer.