Background
Phase III RCT enrolled 3,171 women with operable breast cancer and 0-3 positive nodes (94% node-negative). Tested whether prolonging adjuvant chemotherapy from 4 to 6 cycles improves outcomes.
Interventions and follow up
Arm A: AC q3wk x4 or paclitaxel x4 (4 cycles)
Arm B: AC q3wk x6 or paclitaxel x6 (6 cycles)
Primary endpoint: Recurrence-free survival (RFS)
mFollow up: 5.3yr
Arm B: AC q3wk x6 or paclitaxel x6 (6 cycles)
Primary endpoint: Recurrence-free survival (RFS)
mFollow up: 5.3yr
Results
4-yr RFS (6 vs 4 cycles): 90.9% vs 91.8%; HR 1.03, 95% CI 0.84-1.28, P=.77
4-yr OS (6 vs 4 cycles): 95.3% vs 96.3%; HR 1.12, 95% CI 0.84-1.49, P=.44
Interpretation: No benefit from 6 vs 4 cycles for either AC or single-agent paclitaxel.
4-yr OS (6 vs 4 cycles): 95.3% vs 96.3%; HR 1.12, 95% CI 0.84-1.49, P=.44
Interpretation: No benefit from 6 vs 4 cycles for either AC or single-agent paclitaxel.
Adverse events
Hematologic: More grade 3-4 cytopenias with 6 cycles.
Constitutional: More fatigue with 6 cycles.
Neurologic: More neuropathy with extended paclitaxel.
Overall: Cumulative toxicity argued against extending therapy beyond 4 cycles.
Constitutional: More fatigue with 6 cycles.
Neurologic: More neuropathy with extended paclitaxel.
Overall: Cumulative toxicity argued against extending therapy beyond 4 cycles.
Conclusions
Prolonging AC or single-agent paclitaxel from 4 to 6 cycles does not improve DFS or OS; 4 cycles is sufficient.
Key Limitations
Predominantly node-negative, lower-risk population (94% N0); not powered within subgroups. Single-agent paclitaxel and AC are no longer standard taxane-anthracycline adjuvant regimens. Cycle-number question rather than regimen comparison.
Clinical Context
Supports limiting adjuvant chemotherapy duration; aligns with ASCO/ESMO guidance favoring shorter regimens when no incremental benefit exists. Reinforces 4-cycle backbones (e.g., TC x4, AC x4) in lower-risk early breast cancer.