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J Clin Oncol. 2017 Aug 1;35(22):2507-2514. doi: 10.1200/JCO.2016.70.5640. Epub 2017 May 3.

Long-Term Follow-Up of the Intergroup Exemestane Study.

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James P. Morden, Lucy Kilburn, Claire Snowdon, and Judith M. Bliss, The Institute of Cancer Research; Hanna Nicholas, Cancer Research UK; R. Charles Coombes, Imperial College London, London; Gianfilippo Bertelli, Singleton Hospital, Swansea; Robert Coleman, Weston Park Hospital, Sheffield; Lesley Fallowfield, University of Sussex, Brighton; David Dodwell, St James Hospital, Leeds, United Kingdom; Isabel Alvarez, Hospital Donostia, GEICAM Spanish Breast Cancer Group, San Sebastian, Spain; Alan S. Coates, International Breast Cancer Study Group, Bern, Switzerland, and University of Sydney, Sydney, Australia; Jacek Jassem, Medical University of Gdansk, Gdansk, Poland; Stephen Jones, US Oncology Research, The Woodlands, TX; Per E. Lønning, University of Bergen and Haukeland University Hospital, Bergen, Norway; Olaf Ortmann, University Medical Center Regensburg, Regensburg, Germany; Cornelis van de Velde, Leiden University Medical Centre, Leiden, the Netherlands; Jørn Andersen, Aarhus University Hospital, Aarhus, Denmark; Lucia Del Mastro, IRCCS Azienda Ospedaliera Universitaria San Martino IST, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy; Stig Holmberg, Sahlgrenska Universitetssjukhuset, Goteborg, Sweden; and Robert Paridaens, Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium.


Purpose The Intergroup Exemestane Study, an investigator-led study of 4,724 postmenopausal patients with early breast cancer (clinical trial information: ISRCTN11883920), has previously demonstrated that a switch from adjuvant endocrine therapy after 2 to 3 years of tamoxifen to exemestane was associated with clinically relevant improvements in efficacy. Here, we report the final efficacy analyses of this cohort. Patients and Methods Patients who remained disease free after 2 to 3 years of adjuvant tamoxifen were randomly assigned to continue tamoxifen or switch to exemestane to complete a total of 5 years of adjuvant endocrine therapy. Given the large number of non-breast cancer-related deaths now reported, breast cancer-free survival (BCFS), with censorship of intercurrent deaths, was the primary survival end point of interest. Analyses focus on patients with estrogen receptor-positive or unknown tumors (n = 4,599). Results At the time of the data snapshot, median follow-up was 120 months. In the population that was estrogen receptor positive or had unknown estrogen receptor status, 1,111 BCFS events were observed with 508 (22.1%) of 2,294 patients in the exemestane group and 603 (26.2%) of 2,305 patients in the tamoxifen group. The data corresponded to an absolute difference (between exemestane and tamoxifen) at 10 years of 4.0% (95% CI, 1.2% to 6.7%), and the hazard ratio (HR) of 0.81 (95% CI, 0.72 to 0.92) favored exemestane. This difference remained in multivariable analysis that was adjusted for nodal status, prior use of hormone replacement therapy, and prior chemotherapy (HR, 0.80; 95% CI, 0.71 to 0.90; P < .001). A modest improvement in overall survival was seen with exemestane; the absolute difference (between exemestane and tamoxifen) at 10 years in the population that was estrogen receptor positive or had unknown estrogen receptor status was 2.1% (95% CI, -0.5% to 4.6%), and the HR was 0.89 (95% CI, 0.78 to 1.01; P = .08). For the intention-to-treat population, the absolute difference was 1.6% (95% CI, -0.9% to 4.1%); the HR was 0.91 (95% CI, 0.80 to 1.03, P = .15). No statistically significant difference was observed in the proportion of patients who reported a fracture event in the post-treatment period. Conclusion The Intergroup Exemestane Study and contemporaneous studies have established that a strategy of switching to an aromatase inhibitor after 2 to 3 years of tamoxifen can lead to sustained benefits in terms of reduction of disease recurrence and breast cancer mortality.

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