NSABP-B15 trial

Background

RCT in women with primary operable, node-positive breast cancer, randomized to adjuvant treatment 2-5 weeks after surgery to compare AC against CMF and AC followed by CMF.

Interventions and follow up

Arm A: AC (doxorubicin/cyclophosphamide) 60/600 q21d x4
Arm B: AC x4, then CMF 6mo later x3
Arm C: Conventional CMF x6 (cyclophosphamide 100 d1-14; methotrexate 40 d1,d8; 5-FU 600 d1,d8; q28d)
Primary endpoint: DFS and OS
mFollow up: 3yr

Results

DFS (AC vs CMF): No significant difference, P=.5
DDFS: No significant difference, P=.5
OS: No significant difference, P=.8
Convenience: AC completed by day 63 vs CMF day 154; fewer physician visits and shorter antiemetic use (12 vs 84 days) with AC.

Adverse events

Hematologic: Neutropenia more frequent with CMF.
Gastrointestinal: Nausea/vomiting and mucositis with CMF; nausea with AC.
Dermatologic: Alopecia with AC.
Cardiac: Cardiotoxicity with AC; acute toxicities generally manageable.

Conclusions

AC x4 is equivalent to CMF x6 with greater convenience and shorter duration, establishing AC as a backbone of adjuvant chemotherapy in node-positive breast cancer.

Key Limitations

Short 3-yr follow-up for survival endpoints. No HER2/receptor stratification (era predates). Equivalence inferred from non-significant differences rather than formal non-inferiority design.

Clinical Context

Foundational trial establishing AC as a short, convenient anthracycline backbone later built upon by taxane-containing regimens (CALGB 9344, 9741). Informs ASCO/ESMO adjuvant chemotherapy frameworks for node-positive disease.

References