Background
Letrozole (Femara) Versus Anastrozole Clinical Evaluation (FACE). Phase III open-label RCT of 4,136 postmenopausal women with HR+, node-positive early breast cancer comparing two nonsteroidal aromatase inhibitors.
Interventions and follow up
Arm A: Letrozole 2.5mg daily × 5yr
Arm B: Anastrozole 1mg daily × 5yr
Primary endpoint: 5-yr DFS
Secondary endpoints: OS and safety
mFollow up: ~65mo
Arm B: Anastrozole 1mg daily × 5yr
Primary endpoint: 5-yr DFS
Secondary endpoints: OS and safety
mFollow up: ~65mo
Results
5-yr DFS, letrozole vs anastrozole: 84.9% vs 82.9% (HR 0.93, 95%CI 0.80-1.07, P=.3150).
5-yr OS, letrozole vs anastrozole: 89.9% vs 89.2% (HR 0.98, 95%CI 0.82-1.17, P=.7916).
5-yr OS, letrozole vs anastrozole: 89.9% vs 89.2% (HR 0.98, 95%CI 0.82-1.17, P=.7916).
Adverse events
Grade 3-4 events (letrozole vs anastrozole):
Musculoskeletal: arthralgia 3.9% vs 3.3%; myalgia 0.8% vs 0.7%.
Cardiovascular: hypertension 1.2% vs 1.0%.
Vasomotor: hot flushes 0.8% vs 0.4%.
Respiratory: dyspnea 0.8% vs 0.5%.
Psychiatric: depression 0.8% vs 0.6%.
Musculoskeletal: arthralgia 3.9% vs 3.3%; myalgia 0.8% vs 0.7%.
Cardiovascular: hypertension 1.2% vs 1.0%.
Vasomotor: hot flushes 0.8% vs 0.4%.
Respiratory: dyspnea 0.8% vs 0.5%.
Psychiatric: depression 0.8% vs 0.6%.
Conclusions
Letrozole and anastrozole have similar efficacy and comparable safety as adjuvant therapy for postmenopausal HR+, node-positive breast cancer.
Key Limitations
Open-label design; equivalence outcome with no efficacy separation. Powered against an assumed difference that was not observed. Node-positive population limits generalizability to lower-risk disease.
Clinical Context
Together with MA.27, FACE confirms that the three third-generation aromatase inhibitors are clinically interchangeable in the adjuvant setting. ASCO and ESMO guidelines list letrozole, anastrozole, and exemestane as equivalent AI options; selection is based on tolerability and access.
References