E2197: Phase III AT (doxorubicin/docetaxel) vs. AC (doxorubicin/cyclophosphamide) in the adjuvant treatment of node positive and high risk node negative breast cancer
Reviewer: Christopher Dolinsky, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 15, 2005
Presenter: L.J. Goldstein
Presenter's Affiliation: Fox Chase Cancer Center, Philadelphia, Pennsylvania
Type of Session: Keynote
- A number of recent studies have shown the benefit of taxane based chemotherapy given in combination with other active agents for high risk breast cancer.
- A regimen including doxorubicin (A) and docetaxel (T), a taxane, has been shown to be beneficial in metastatic breast cancer.
- Combination doxorubicin (A) and cyclophosphamide (C) has been well described as an effective regimen for adjuvant therapy after local treatment in high risk breast cancer patients.
- This trial was designed to compare AC to AT.
Materials and Methods
- Women with N1 disease (1-3 positive nodes) or node negative and T > 1cm disease were randomized to 4 cycles of AT (60mg/m2/60mg/m2) given every 3 weeks or 4 cycles of AC (60mg/m2/600mg/m2) given every 3 weeks.
- Patients with ER and/or PR positive tumors were treated with 5 years of tamoxifen.
- Patients were stratified by a variety of factors: menopausal status, nodal stage, hormone receptor status.
- The two arms were well balanced in terms of disease and demographic factors including: age, hormone receptor status, menopausal status, tumor size, nodal stage, tumor grade and type of surgery.
- 2885 patients were enrolled and eligible for analysis.
- Median age was 51 years old.
- 64% of patients were ER positive, and 65% of patients were node negative.
- Median tumor size was 2 cm.
- The primary endpoint was disease free survival.
- Median follow-up time was 59 months.
- There was no significant difference in either disease free survival (hazard ratio 1.03, p=0.48) or overall survival (hazard ratio 1.09)
- When subgroups were analyzed separately, no significant differences were noted between the two arms.
- The 4 year disease free survival for both arms was 87%.
- Febrile neutropenia was more common in the AT arm than the AC arm, 28% vs 10%.
- 2 deaths related to treatment were seen in the AT group, and no deaths related to treatment were seen in the AC group.
- 18 cases of congestive heart failure were noted in the AT group, and 10 were noted in the AC group, but this difference was not statistically significantly different.
- It does not appear that there is a significant difference between these two regimens in terms of disease free survival
- The disease free survival in the control AC arm of 87% was higher than expected based on historical controls, which would predict a disease free survival of 70% for this regimen.
- Longer follow-up will not likely alter these results.
- Analyses of various subsets will be performed and presented in the future.