NCIC CTG MA.27 trial

Background

NCIC CTG MA.27. Phase III RCT of 7,576 postmenopausal women with HR+ early breast cancer, comparing the steroidal aromatase inhibitor exemestane with the nonsteroidal AI anastrozole as adjuvant therapy.

Interventions and follow up

Arm A: Exemestane 25mg daily × 5yr
Arm B: Anastrozole 1mg daily × 5yr
Primary endpoint: Event-free survival (EFS), powered to detect a 2.4% absolute improvement
mFollow up: 4.1yr

Results

4-yr EFS, exemestane vs anastrozole: 91.0% vs 91.2% (stratified HR 1.02, 95%CI 0.87-1.18, P=.85).
OS: similar between arms, no significant difference.
Distant DFS: no significant difference.

Adverse events

Shared (both AIs): hot flashes, arthralgias, myalgias, reduced bone density.
More frequent with anastrozole: osteoporosis/osteopenia, hypertriglyceridemia, hypercholesterolemia, vaginal bleeding.
More frequent with exemestane: mild liver enzyme elevations, rare atrial fibrillation.

Conclusions

Exemestane and anastrozole have equivalent efficacy as adjuvant therapy for postmenopausal HR+ breast cancer, with modestly different toxicity profiles (less lipid and bone effect with exemestane).

Key Limitations

Noninferiority/equivalence outcome with relatively short 4.1yr follow-up for late-recurring HR+ disease. Event rates were lower than projected, reducing power. AE differences were modest and of uncertain long-term clinical significance.

Clinical Context

Supports the interchangeability of available third-generation AIs (exemestane, anastrozole, letrozole) in postmenopausal adjuvant therapy, consistent with the FACE trial (letrozole vs anastrozole). ASCO and ESMO guidelines treat these AIs as equivalent options; choice is driven by tolerability and cost.

References