Concurrent doxorubicin plus docetaxel is not more effective than concurrent doxorubicin plus cyclophosphamide in operable breast cancer with 0 to 3 positive axillary nodes: North American Breast Cancer Intergroup Trial E 2197

Abstract

Purpose: The combination of doxorubicin and cyclophosphamide (AC) is a standard adjuvant regimen. Doxorubicin and docetaxel (AT) is one of the most active cytotoxic regimens for metastatic breast cancer. The purpose of this trial was to determine whether adjuvant AT improved disease-free survival compared with AC in operable breast cancer.

Patients and methods: Women with invasive breast cancer were eligible if there were one to three positive lymph nodes or if the node-negative tumor was greater than 1 cm. Patients were randomly assigned after surgery to receive doxorubicin (60 mg/m(2)) plus either cyclophosphamide (600 mg/m(2); AC) or docetaxel (60 mg/m(2); AT) given every 3 weeks for four cycles, followed by hormone therapy for patients with estrogen receptor (ER) and/or progesterone receptor (PR)-positive tumors.

Results: There were 2,882 eligible patients enrolled. After a median follow-up of 79.5 months, there was no significant difference in disease-free survival (DFS; 85% in both arms) or overall survival (91% v 92%) at 5 years. The hazard ratio for AC versus AT was 1.02 (95% CI for DFS, 0.86 to 1.22; P = .78). In an exploratory analysis of prespecified stratification factors by ER and PR expression there were trends toward improved DFS for AT in ER/PR-negative disease. Grade 3 neutropenia associated with fever or infection occurred more often with AT (26% v 10%; P < .05).

Conclusion: AT did not improve DFS or overall survival in this population, and was associated with more toxicity.

Fig A1.

Kaplan-Meier curve overall survival. Solid yellow curve indicates doxorubicin and docetaxel (AT); dotted blue curve indicates doxorubicin and cyclophosphamide (AC).

Fig 1.

CONSORT diagram. AT, doxorubicin and docetaxel; AC, doxorubicin and cyclophosphamide; DFS, disease-free survival.

Fig 2.

Kaplan-Meier curve for disease-free survival. Solid yellow curve indicates doxorubicin and docetaxel (AT); dotted blue curve indicates doxorubicin and cyclophosphamide (AC).

Fig 3.

Forest plot: disease-free survival by subgroups. ER, estrogen receptor; PR, progesterone receptor; AC, doxorubicin and cyclophosphamide; AT, doxorubicin and docetaxel.

Fig 4.

Kaplan-Meier disease-free survival curves by estrogen receptor (ER)/progesterone receptor (PR) subgroups: solid yellow curves indicates doxorubicin and docetaxel (AT); dotted blue curves indicates doxorubicin and cyclophosphamide (AC). (A) ER negative, PR negative. (B): ER negative, PR positive (C) ER positive, PR negative. (D) ER positive, PR positive.