Background
Italian Tamoxifen Anastrozole (ITA) trial. Phase III RCT of 448 postmenopausal women with HR+, node-positive early breast cancer comparing continued tamoxifen with switching to anastrozole after 2-3yr.
Interventions and follow up
Arm A: Tamoxifen 20mg/d × 5yr
Arm B: Tamoxifen 20mg/d × 2-3yr then Anastrozole 1mg/d to complete 5yr
Primary endpoint: DFS
mFollow up: 36mo
Arm B: Tamoxifen 20mg/d × 2-3yr then Anastrozole 1mg/d to complete 5yr
Primary endpoint: DFS
mFollow up: 36mo
Results
Event-free survival (sequential vs tamoxifen): HR 0.35, 95%CI 0.20-0.63, P=.0002, favoring switching to anastrozole.
Recurrence-free survival: HR 0.35, 95%CI 0.18-0.68, P=.001, favoring switching.
OS: not significantly different (underpowered).
Recurrence-free survival: HR 0.35, 95%CI 0.18-0.68, P=.001, favoring switching.
OS: not significantly different (underpowered).
Adverse events
Tamoxifen vs sequential therapy:
Gynecologic: serious gynecologic events and endometrial abnormalities more frequent with tamoxifen.
Overall: more treatment-related serious adverse events in the tamoxifen arm.
Gynecologic: serious gynecologic events and endometrial abnormalities more frequent with tamoxifen.
Overall: more treatment-related serious adverse events in the tamoxifen arm.
Conclusions
Switching to anastrozole after 2-3yr of tamoxifen significantly improved EFS and RFS vs continued tamoxifen in node-positive postmenopausal HR+ patients.
Key Limitations
Small (n=448), node-positive cohort with short 36mo follow-up. Trial closed early after ATAC results and an interim ITA analysis, inflating effect-size estimates. Underpowered for OS; wide confidence intervals.
Clinical Context
ITA was an early proof-of-concept for the switch strategy, later supported by ABCSG-8/ARNO 95 and pooled in the EBCTCG meta-analysis. ASCO and ESMO guidelines endorse sequencing tamoxifen to an AI as an acceptable adjuvant approach for postmenopausal HR+ disease.