A Randomized Trial of Letrozole in Postmenopausal Women after Five Years of Tamoxifen Therapy for Early-Stage Breast Cancer
- Study type
- Clinical trial
- Study name
- MA.17
- Design
- Randomised, double-blind, placebo-controlled trial
- Sample size
- 5187 women
- Source
- N Engl J Med · 2003
In plain words
This study looked at postmenopausal women who had taken tamoxifen for five years for breast cancer and then received letrozole or a placebo. In the letrozole group, the cancer came back, or a new cancer appeared in the other breast, less often. Side effects such as hot flushes and joint and muscle pain were more common in the letrozole group. The decision to continue hormone therapy should be made with the treating doctor and based on each patient's situation.
Key results
Treatment arms and regimens
Five years of letrozole after completing five years of tamoxifen.
Oral letrozole once daily (label dose: 2.5 mg); planned duration 5 years, but the trial was unblinded early after the interim analysis.
Placebo after completing five years of tamoxifen.
Oral placebo once daily.
Source of the regimen details: Abstract of the paper, ClinicalTrials.gov NCT00003140 (oral letrozole once daily) and the FDA label for Femara (dose 2.5 mg daily; MA-17 is the basis of approval for extended adjuvant therapy)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Postmenopausal women with breast cancer who had completed five years of tamoxifen therapy. Other inclusion criteria are not given in the abstract.
Endpoints
Primary endpoint: disease-free survival. Among other endpoints, the abstract reports overall survival and adverse events (including osteoporosis and fractures).
Safety and side effects
Low-grade hot flushes, arthritis, arthralgia and myalgia were more common in the letrozole group, but vaginal bleeding was less frequent. New diagnoses of osteoporosis were reported in 5.8% of women in the letrozole group and 4.5% in the placebo group (P=0.07), and fracture rates were similar in the two groups. Rates of grade 3 or higher adverse events are not given in the abstract.
Clinical significance and place in guidelines
This trial showed that adding five years of letrozole after tamoxifen improves disease-free survival in postmenopausal women, and for this reason the data monitoring committee recommended early termination of the study. At the time of the report there was no significant difference in overall survival (P=0.25). The current status of this approach in clinical guidelines should be checked separately, because the abstract gives no information about it.
Limitations
The results are based on the first interim analysis with a short median follow-up (2.4 years). The overall survival difference was not significant, and the long-term effect of letrozole on osteoporosis and fractures cannot be judged definitively with such short follow-up. Other details should be checked in the full text of the paper.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.