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Whether given every week or every 3 weeks after standard chemotherapy, paclitaxel and docetaxel confer similar disease-free survival in women with operable breast cance, the North American Breast Cancer Intergroup Trial E1199 has found.
Planned secondary comparisons suggest, however, that weekly paclitaxel (Taxol) and docetaxel (Taxotere) given every 3 weeks are superior in some subgroups. Study chair Dr. Joseph A. Sparano of the Eastern Cooperative Oncology Group reported the results.
E1199 randomized 4,950 patients with stage IIA, IIB, or IIIA axillary node-positive breast cancer or high-risk node-negative breast cancer to standard chemotherapy with four cycles of doxorubicin 60 mg/m² and cyclophosphamide 600 mg/m² every 3 weeks followed by a taxane-based regimen:
At a median follow-up of 63.8 months, Dr. Sparano reported 5-year disease-free survival was 76.9% with paclitaxel every 3 weeks, 81.5% with weekly paclitaxel, 81.2% with docetaxel every 3 weeks, and 77.6% with weekly docetaxel.
Five-year overall survival also was similar: 89.7% with weekly paclitaxel, 87.3% with docetaxel every 3 weeks, 86.5% with paclitaxel every 3 weeks, and 86.2% with docetaxel every week.
"Compared with paclitaxel, docetaxel did not improve disease-free survival, given either every week or every 3 weeks," said Dr. Sparano, professor of medicine at Albert Einstein College of Medicine, Bronx, N.Y. He added, however, that interactions confounded the comparisons. For example, patients with hormone receptor-positive breast cancer had significantly better results with docetaxel every 3 weeks than with paclitaxel every 3 weeks (P = .03).
The greatest treatment effect was observed in patients with hormone receptor-negative disease on weekly paclitaxel. They fared significantly better (P = .02) than those given paclitaxel every 3 weeks. Dr. Sparano noted this analysis "should be considered with caution as a sufficient number of events with full information have not occurred."
Docetaxel every 3 weeks was associated with more severe neutropenia, febrile neutropenia, and infection; weekly paclitaxel with more neutropenia.
Discussant Dr. Robert Carlson, professor of medicine at Stanford (Calif.) University, said taxanes may be more beneficial in estrogen receptor-negative and HER2-positive disease. He urged comparisons of dose-dense paclitaxel to docetaxel schedules and to weekly paclitaxel and research to find biomarkers for resistance or sensitivity to taxanes.
Sparano J.A. et al. Phase III study of doxorubicin-cyclophosphamide followed by paclitaxel or docetaxel given every 3 weeks or weekly in operable breast cancer: Results of Intergroup Trial E1199. Abstract 516.
Commentary |
This fascinating study is a landmark analysis demonstrating that variations in taxane and taxane schedule result in similar improvement of outcome when given after adjuvant doxorubin and cyclophosphamide. Only 75% of patients completed all doses of weekly docetaxel vs. 87% with every-3-weeks dosing. Every-3-weeks docetaxel was associated with substantially more febrile neutropenia; paclitaxel with more peripheral neuropathy, particularly with weekly dosing. Although this assessment is still early in terms of breast cancer events, analysis of disease-free survival suggested greater benefit from weekly paclitaxel and every-3-weeks docetaxel, compared with every-3-weeks paclitaxel. Subset analysis also saw efficacy differences based on schedule for hormone receptor-negative and -positive subgroups, again confirming the importance of adjuvant trials focused on biologic subsets. This approach will also help us to understand the effects of targeted biologic agents such as those used in antiangiogenic therapy. — Hope S. Rugo, M.D.
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