ABCG 8 trial

Background

ABCSG-8 (Austrian Breast and Colorectal Cancer Study Group 8). Phase III RCT of 3,714 postmenopausal women with operable, HR+, grade 1-2 early breast cancer comparing 5yr tamoxifen with a sequential tamoxifen-to-anastrozole strategy.

Interventions and follow up

Arm A: Tamoxifen 20mg/d × 5yr
Arm B: Tamoxifen 20mg/d × 2yr then Anastrozole 1mg/d × 3yr
Primary endpoint: Recurrence-free survival (RFS)
Secondary endpoints: distant relapse-free survival (DRFS); DFS and OS exploratory
mFollow up: ~5yr

Results

RFS (sequential vs tamoxifen): HR 0.80, 95%CI 0.63-1.01, P=.064.
DRFS: HR 0.78, 95%CI 0.60-0.996, P=.046, favoring sequential therapy.
OS: HR 0.87, 95%CI 0.65-1.16, P=.34 (no significant difference).

Adverse events

Grade 3-4 events were uncommon overall.
Vasomotor/vascular (tamoxifen): more vasomotor symptoms and thromboembolism.
Musculoskeletal/bone (anastrozole): more arthralgia, fractures, and bone loss.

Conclusions

Switching to anastrozole after 2yr of tamoxifen significantly improved DRFS vs 5yr tamoxifen, supporting a sequential endocrine strategy in postmenopausal HR+ early breast cancer.

Key Limitations

Primary RFS endpoint did not reach significance (P=.064); the positive DRFS result was a secondary endpoint. Low-risk, grade 1-2 population with low event rates limits power and generalizability. No upfront-AI comparator arm and no OS benefit.

Clinical Context

ABCSG-8 (with ARNO 95 and ITA) supports the sequential tamoxifen-to-AI approach incorporated into the EBCTCG meta-analysis. ASCO and ESMO guidelines endorse including an AI either upfront or after 2-3yr of tamoxifen for postmenopausal HR+ patients.

References