CALGB 9344 trial

Background

Phase III RCT enrolled 3,121 women with operable, node-positive breast cancer to test (1) doxorubicin dose escalation and (2) addition of sequential paclitaxel after AC.

Interventions and follow up

Arm A: AC x4 (doxorubicin 60/75/90 + cyclophosphamide 600) then paclitaxel 175 mg/m2 x4
Arm B: AC x4 (doxorubicin 60/75/90 + cyclophosphamide 600) then no further therapy
Primary endpoint: DFS and OS
mFollow up: 5yr

Results

Doxorubicin dose effect (DFS, 60/75/90): 69%/66%/67%; no dose effect
Recurrence reduction adding paclitaxel: 17% (adjusted P=.0023; unadjusted P=.0011)
Death reduction adding paclitaxel: 18% (adjusted P=.0064; unadjusted P=.0098)
5-yr DFS (with vs without paclitaxel): 70% vs 65%
5-yr OS (with vs without paclitaxel): 80% vs 77%

Adverse events

Neurologic: Grade 3-4 neuropathy with paclitaxel.
Musculoskeletal: Myalgia with paclitaxel.
Hematologic: Febrile neutropenia with paclitaxel addition.
Cardiac: Increased cardiotoxicity with higher doxorubicin doses.

Conclusions

Adding sequential paclitaxel after AC significantly improves DFS and OS in node-positive breast cancer; escalating doxorubicin above 60 mg/m2 confers no benefit.

Key Limitations

No HER2-directed therapy (predates trastuzumab); benefit later shown to concentrate in HER2+/ER- subsets in retrospective analyses. Three-weekly paclitaxel schedule later superseded by weekly dosing (E1199). Node-positive only.

Clinical Context

Established the taxane-after-anthracycline (AC→T) adjuvant paradigm endorsed by ASCO/ESMO for higher-risk early breast cancer. Foundation later refined by dose-dense scheduling (CALGB 9741) and weekly paclitaxel (E1199).

References