Background
Study of Letrozole Extension (SOLE). Phase III RCT of 4,884 postmenopausal patients with HR+, node-positive breast cancer who had completed 4–6 years of adjuvant endocrine therapy. Tested whether intermittent extended letrozole improves outcomes vs continuous.
Interventions and follow up
Arm A: Continuous letrozole 2.5mg/d po × 5yr
Arm B: Intermittent letrozole (9 months on / 3 months off) over 4yr, then continuous in year 5
Primary endpoint: DFS
mFollow up: 60mo
Arm B: Intermittent letrozole (9 months on / 3 months off) over 4yr, then continuous in year 5
Primary endpoint: DFS
mFollow up: 60mo
Results
5-yr DFS: 87.5% (continuous) vs 85.8% (intermittent); HR 1.08, 95%CI 0.93–1.26; P=.31
OS: No significant difference between arms
OS: No significant difference between arms
Adverse events
Vasomotor: Hot flushes 54% (continuous) vs 53% (intermittent)
Cardiovascular: Hypertension 21% vs 24%
Musculoskeletal: Bone fractures 9% vs 8%
Cardiovascular: Hypertension 21% vs 24%
Musculoskeletal: Bone fractures 9% vs 8%
Conclusions
Intermittent extended letrozole did not improve DFS over continuous therapy, with similar toxicity. Continuous extended letrozole remains the standard schedule, though an intermittent schedule may be reasonable for tolerability.
Key Limitations
Negative trial for its primary hypothesis. Both arms received extended therapy, so the trial does not address whether extension itself is beneficial. Tolerability/quality-of-life advantages of the intermittent schedule were modest. Node-positive enrichment limits generalizability to lower-risk patients.
Clinical Context
Addresses schedule (not duration) of extended endocrine therapy. ASCO/ESMO do not endorse intermittent dosing to improve efficacy; the data support continuous extended AI as standard, with intermittent dosing only as a tolerability accommodation.