The phase III SOLE trial has shown no disease-free survival benefit with extended intermittent vs continuous adjuvant letrozole in postmenopausal women with breast cancer. These findings were reported by Colleoni et al in The Lancet Oncology. As noted by the investigators, the findings suggest an absence of harm of temporary breaks from treatment in patients who may require them.
In the open-label trial, 4,851 women from 240 sites in 22 countries who had completed 4 to 6 years of adjuvant endocrine therapy were randomized between December 2007 and October 2012 to receive extended intermittent letrozole (n = 2,425) or continuous letrozole (n = 2,426). Intermittent treatment consisted of 2.5 mg/d for 9 months followed by a 3-month break in years 1 to 4 and then 2.5 mg/d during every month in year 5. Continuous treatment consisted of 2.5 mg/d for 5 years.
Patients were postmenopausal women of any age with hormone receptor–positive, lymph node–positive, and operable breast cancer who had received local treatment (surgery with or without radiotherapy), were clinically free of breast cancer at enrollment, and had no evidence of recurrent disease at any time before randomization. Randomization was stratified by the type of prior endocrine therapy. The primary endpoint was disease-free survival in the intent-to-treat population.
After a median follow-up of 60 months, estimated 5-year disease-free survival was 85.8% in the intermittent letrozole group vs 87.5% in the continuous letrozole group (hazard ratio = 1.08, P = .31). No heterogeneity of treatment effect was observed across patient subgroups. Estimated 5-year rates were 90.9% vs 91.2% for freedom from breast cancer (HR = 0.98, P =.84), 93.2% vs 92.5% for freedom from distant recurrence (HR = 0.88, P = .25), and 94.3% vs 93.7% for overall survival (HR = 0.85, P = .16).
The most common grade ≥ 3 adverse events in the intermittent vs continuous treatment groups were hypertension (24% vs 21%) and arthralgia (6% vs 6%). Grade ≥ 3 cerebrovascular ischemia occurred in 1% vs 1%, grade ≥ 3 central nervous system hemorrhage in 1% vs 1%, and grade ≥ 3 cardiac ischemia in 1% vs 1%. Overall, 13 patients (< 1%) in the intermittent group and 10 patients (< 1%) in the continuous group died during study treatment.
The investigators concluded: “In postmenopausal women with hormone receptor–positive breast cancer, extended use of intermittent letrozole did not improve disease-free survival compared with continuous use of letrozole. An alternative schedule of extended adjuvant endocrine therapy with letrozole, including intermittent administration, might be feasible, and the results of the SOLE trial support the safety of temporary treatment breaks in selected patients who might require them.”
The study was funded by the International Breast Cancer Study Group and Novartis.
Marco Colleoni, MD, of the European Institute of Oncology, Milan, is the corresponding author of The Lancet Oncology article.
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