Paclitaxel (T) following doxorubicin/cyclophosphamide(AC) as adjuvant chemotherapy for node positive breast cancer: Results from NSABP B-28

Reviewer: Walter Sall, MD
OncoLink
Last Modified: May 31, 2003

Presenter: E. P. Mamounas
Presenter's Affiliation: NSABP
Type of Session: Scientific

Background

This prospective randomized trial intended to determine whether the addition of T to AC chemotherpy provided a benefit in node positive patients with operable breast cancer.
Though definitive data regarding the benefit of adjuvant taxanes in node positive breast cancer are sparse, their use has become quite common in most oncology practices for this patient group.

Materials and Methods

Between 8/95 and 5/98, 3060 patients were randomized. Patients older than 50 and ER (+) patients less than 50 received tamoxifen for 5 years following completion of chemotherapy.
Patients were randomized to receive either adjuvant AC alone or AC + T.
Patients were stratified by number of nodes, use of tamoxifen and type of surgery performed.
Standard dose AC chemotherapy was given every 21 days for four cycles. T was given every 21 days for 4 cycles.
Endpoints were DFS abd OS. This was an intention to treat analysis and represents the final analysis of this study after three prior interim analyses.

Results

Patient and tumor characteristics were evenly distributed between the two groups.
Median follow-up was 64.6 months.
70% of patients had 1-3 positive nodes, 26% had 4-9 positive nodes and 4% had 10 or more positive nodes.
No overall survival (OS) benefit was seen. 5 year OS was 85% in both groups.
5 year Disease Free Survival (DFS) was 76% with taxol and 72% without (p=0.008)

Author's Conclusions

Tamoxifen improves DFS with a relative risk of 0.83% (p=0.008).
T toxicity was acceptable. 28% of patients had grade III+ toxicity during AC. 34% of patients had grade III+ toxicity during T therapy.
There was no interaction between treatment effect and receptor status for all endpoints.
DFS benefit was similar to that seen in the CALGB 9844 trial.
This trial does not confirm the hypothesis that T provides no benefit to ER (+)patients or patients receiving tamoxifen.

Clinical/Scientific Implications

Though T was not seen to provide a survival benefit to node (+) patients in this trial, it does show an important DFS benefit. This follows the conclusion of the previous CALGB 9844 trial which supports the use of taxanes in the adjuvant treatment of operable node positive breast cancer. The moderate neurologic and hematologic toxicity of T is justified by the benefit seen in this high risk patient group. Future trials with larger numbers may be able to show a survival benefit. Notably, in this trial, ER(+) and tamoxifen treated patients appeared to benefit from T just as other patients did. This contradicts the assertion of some that paclitaxel does not benefit this particular susbset of node (+) patients.

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