Originally published as JCO Early Release 10.1200/JCO.2007.14.0459 on March 10 2008

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Letrozole Compared With Tamoxifen for Elderly Patients With Endocrine-Responsive Early Breast Cancer: The BIG 1-98 Trial

Diana Crivellari, Zhuoxin Sun, Alan S. Coates, Karen N. Price, Beat Thürlimann, Henning Mouridsen, Louis Mauriac, John F. Forbes, Robert J. Paridaens, Monica Castiglione-Gertsch, Richard D. Gelber, Marco Colleoni, István Láng, Lucia Del Mastro, Laurence Gladieff, Manuela Rabaglio, Ian E. Smith, Jacquie H. Chirgwin, Aron Goldhirsch

From the Centro di Riferimento Oncologico, Aviano; Department of Medicine. European Institute of Oncology, Milan; National Cancer Research Institute, Genoa, Italy; International Breast Cancer Study Group (IBCSG) Statistical Center, Dana-Farber Cancer Institute; Harvard School of Public Health and Frontier Science and Technology Research Foundation, Boston, MA; IBCSG and University of Sydney, Sydney; Australian New Zealand Breast Cancer Trials Group, University of Newcastle, Calvary Mater Newcastle, Newcastle; Box Hill and Maroondah Hospitals, Melbourne, Australia; Senology Center of Eastern Switzerland, Kantonsspital, St Gallen; IBCSG Coordinating Center, Bern; Oncology Institute of Southern Switzerland, Bellinzona, Switzerland; Danish Breast Cancer Cooperative Group, Rigshospitalet, Copenhagen, Denmark; Fédération Nationale des Centres de Lutte Contre le Cancer, Institut Bergonié, Bordeaux; Institut Claudius Régaud, Toulouse, France; Department of Medical Oncology, University Hospital Gasthuisberg, Catholic University of Leuven, Belgium; National Institute of Oncology, Budapest, Hungary; and The Royal Marsden Hospital, London, United Kingdom

Corresponding author: Diana Crivellari, MD, IBCSG Coordinating Center, Effingerstrasse 40, CH-3008 Bern, Switzerland; e-mail: dcrivellari{at}cro.it

Purpose: To explore potential differences in efficacy, treatment completion, and adverse events (AEs) in elderly women receiving adjuvant tamoxifen or letrozole for five years in the Breast International Group (BIG) 1-98 trial.

Methods: This report includes the 4,922 patients allocated to 5 years of letrozole or tamoxifen in the BIG 1-98 trial. The median follow-up was 40.4 months. Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was used to examine the patterns of differences in disease-free survival and incidences of AEs according to age. In addition, three categoric age groups were defined: "younger postmenopausal" patients were younger than 65 years (n = 3,127), "older" patients were 65 to 74 years old (n = 1,500), and "elderly" patients were 75 years of age or older (n = 295).

Results: Efficacy results for subpopulations defined by age were similar to the overall trial results: Letrozole significantly improved disease-free survival (DFS), the primary end point, compared with tamoxifen. Elderly patients were less likely to complete trial treatment, but at rates that were similar in the two treatment groups. The incidence of bone fractures, observed more often in the letrozole group, did not differ by age. In elderly patients, letrozole had a significantly higher incidence of any grade 3 to 5 protocol-specified non-fracture AE compared with tamoxifen (P = .002), but differences were not significant for thromboembolic or cardiac AEs.

Conclusion: Adjuvant treatment with letrozole had superior efficacy (DFS) compared with tamoxifen in all age groups. On the basis of a small number of patients older than 75 years (6%), age per se should not unduly affect the choice of adjuvant endocrine therapy.

published online ahead of print at www.jco.org on March 10, 2008.

Sponsored by Novartis, the Swedish Cancer Society, The Cancer Council Australia, Australian New Zealand Breast Cancer Trials Group, Frontier Science and Technology Research Foundation, Swiss Group for Clinical Cancer Research (SAKK), National Cancer Institute Grant No. CA-75362, Cancer Research Switzerland/Oncosuisse, and the Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK).

Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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