Background
Intergroup Exemestane Study (IES). Phase III, double-blind RCT of 4,742 postmenopausal women with HR+ (or unknown) early breast cancer who were disease-free after 2–3 years of adjuvant tamoxifen. Tested switching to exemestane vs continuing tamoxifen to complete 5 years of endocrine therapy.
Interventions and follow up
Arm A: Tamoxifen 20mg/d po × 5yr
Arm B: Tamoxifen 20mg/d po × 2.5–3yr then switch to exemestane 25mg/d po to complete 5yr
Primary endpoint: DFS
mFollow up: 30.6mo
Arm B: Tamoxifen 20mg/d po × 2.5–3yr then switch to exemestane 25mg/d po to complete 5yr
Primary endpoint: DFS
mFollow up: 30.6mo
Results
3-yr DFS: 86.8% (tamoxifen) vs 91.5% (sequential exemestane); HR 0.68, 95%CI 0.56–0.82; P<.001
OS: HR 0.88, 95%CI 0.67–1.16; P=.37
Contralateral breast cancer: Reduced with switch to exemestane (relative risk ~0.56)
OS: HR 0.88, 95%CI 0.67–1.16; P=.37
Contralateral breast cancer: Reduced with switch to exemestane (relative risk ~0.56)
Adverse events
Gynecologic: Endometrial cancer lower with exemestane (0.21% vs 0.46% with continued tamoxifen)
Vascular: Fewer thromboembolic events with exemestane
Musculoskeletal: More arthralgia and osteoporosis with exemestane
Vascular: Fewer thromboembolic events with exemestane
Musculoskeletal: More arthralgia and osteoporosis with exemestane
Conclusions
Switching from tamoxifen to exemestane after 2–3 years improves DFS (but not OS) and reduces contralateral breast cancer and endometrial cancer compared with completing 5 years of tamoxifen.
Key Limitations
No OS benefit demonstrated. Short median follow-up (30.6mo) at primary report. Predates routine use of upfront aromatase inhibitors; comparator is the now-superseded 5-year tamoxifen monotherapy. Bone-density and fracture risk with exemestane requires monitoring not standardized at the time.
Clinical Context
A foundational "switch" trial supporting incorporation of an aromatase inhibitor during the first 5 years of adjuvant endocrine therapy for postmenopausal HR+ breast cancer. ASCO and ESMO endorse including an AI either upfront or via switch strategy; IES helped establish the sequential approach.