Disease-Related Outcomes With Long-Term Follow-Up: An Updated Analysis of the Intergroup Exemestane Study

Bliss, J.M.; Kilburn, L.S.; Coleman, R.E.; Forbes, J.F.; Coates, A.S.; Jones, S.E.; ... ; Coombes, R.C. (2011)

Article / Letter to editor

PURPOSEIntergroup Exemestane Study (IES), an investigator-led study in 4,724 postmenopausal patients with early-stage breast cancer has demonstrated clinically important benefits from switching adjuvant endocrine therapy after 2 to 3 years of tamoxifen to exemestane. Now, with longer follow-up, a large number of non-breast cancer-related events have been reported. Exploratory analyses describe breast cancer-free survival (BCFS) and explore incidence and patterns of the different competing events. PATIENTS AND METHODSPatients who were disease-free after 2 to 3 years of adjuvant tamoxifen were randomly assigned to continue tamoxifen or switch to exemestane to complete 5 years of adjuvant endocrine therapy. At this planned analysis, the median follow-up was 91 months. Principal analysis focuses on 4,052 patients with estrogen receptor (ER) -positive and 547 with ER-unknown tumors.ResultsIn all, 930 BCFS events have been reported (exemestane, 423; tamoxifen, 507), giving an unadjusted hazard ratio (HR) of 0.81 (95% CI, 0.71 to 0.92; P = .001) in favor of exemestane in the ER-positive/ER unknown group. Analysis partitioned at 2.5 years after random assignment showed that the on-treatment benefit of switching to exemestane (HR, 0.60; 95% CI, 0.48 to 0.75; P < .001) was not lost post-treatment, but that there was no additional gain once treatment had ceased (HR, 0.94; 95% CI, 0.80 to 1.10; P = .60). Improvement in overall survival was demonstrated, with 352 deaths in the exemestane group versus 405 deaths in the tamoxifen group (HR, 0.86; 95% CI, 0.75 to 0.99; P = .04). Of these, 222 were reported as intercurrent deaths (exemestane, 107; tamoxifen, 115). CONCLUSIONThe protective effect of switching to exemestane compared with continuing on tamoxifen on risk of relapse or death was maintained for at least 5 years post-treatment and was associated with a continuing beneficial impact on overall survival.

• All authors: Bliss, J.M.; Kilburn, L.S.; Coleman, R.E.; Forbes, J.F.; Coates, A.S.; Jones, S.E.; Jassem, J.; Delozier, T.; Andersen, J.; Paridaens, R.; Velde, C.J.H. van de; Lonning, P.E.; Morden, J.; Reise, J.; Cisar, L.; Menschik, T.; Coombes, R.C.
• Date: 2011-11-21
• Journal: Journal of Clinical Oncology
• DOI: doi:10.1200/JCO.2010.33.7899