Background
Investigation on the Duration of Extended Adjuvant Letrozole (IDEAL / BOOG 2006-05). Phase III RCT of 1,824 postmenopausal patients with HR+ breast cancer who had completed ~5 years of adjuvant endocrine therapy (tamoxifen, AI, or both). Compared two durations of extended letrozole.
Interventions and follow up
Arm A: Letrozole × 2.5yr after ~5yr of prior endocrine therapy
Arm B: Letrozole × 5yr after ~5yr of prior endocrine therapy
Primary endpoint: DFS
mFollow up: 6.6yr
Arm B: Letrozole × 5yr after ~5yr of prior endocrine therapy
Primary endpoint: DFS
mFollow up: 6.6yr
Results
5-yr DFS: 82.0% (2.5yr) vs 83.4% (5yr); HR 0.92, 95%CI 0.74–1.16; P=.49
5-yr OS: 93.5% vs 92.6%; HR 1.04, 95%CI 0.78–1.38; P=.79
Second primary breast cancer (incl. contralateral): 3.1% vs 1.1%; HR 0.39, 95%CI 0.19–0.81; P=.01
5-yr OS: 93.5% vs 92.6%; HR 1.04, 95%CI 0.78–1.38; P=.79
Second primary breast cancer (incl. contralateral): 3.1% vs 1.1%; HR 0.39, 95%CI 0.19–0.81; P=.01
Adverse events
Vasomotor: Hot flushes 10.5% (2.5yr) vs 13.1% (5yr)
Musculoskeletal: New osteoporosis 7.5% vs 12.7%; bone fractures 4.7% vs 6.3%
Musculoskeletal: New osteoporosis 7.5% vs 12.7%; bone fractures 4.7% vs 6.3%
Conclusions
No DFS or OS difference between 2.5 vs 5 years of extended letrozole after an initial 5 years of endocrine therapy. Prolonged letrozole was associated with a ~1% absolute reduction in second primary breast cancers but more endocrine-related side effects.
Key Limitations
Heterogeneous prior endocrine therapy. The DFS difference for the second-primary endpoint was a secondary finding. No molecular/genomic risk stratification to identify patients who might benefit from extension. Underpowered for OS.
Clinical Context
Part of the body of extended-endocrine-therapy trials (with MA.17R, NSABP B-42, ABCSG-16). Supports that extending beyond ~5 additional years confers minimal recurrence benefit at the cost of toxicity. ASCO/ESMO recommend individualizing extended endocrine therapy by recurrence risk and tolerability.