Long-Term Follow-Up of the E1199 Phase III Trial Evaluating the Role of Taxane and Schedule in Operable Breast Cancer.

Abstract

PURPOSE:

To determine long-term outcomes in a clinical trial evaluating the role of taxane type and schedule in operable breast cancer and evaluate the impact of obesity and black race on outcome.

PATIENTS AND METHODS:

A total of 4,954 eligible women with stage II to III breast cancer treated with four cycles of doxorubicin plus cyclophosphamide were randomly assigned to receive paclitaxel or docetaxel every 3 weeks for four doses or weekly for 12 doses using a 2 × 2 factorial design. The primary end point was disease-free survival (DFS). Results are expressed as hazard ratios (HRs) from Cox proportional hazards models. All P values are two sided.

RESULTS:

When compared with the standard every-3-week paclitaxel arm, after a median follow-up of 12.1 years, DFS significantly improved and overall survival (OS) marginally improved only for the weekly paclitaxel (HR, 0.84; P = .011 and HR, 0.87; P = .09, respectively) and every-3-week docetaxel arms (HR, 0.79; P = .001 and HR, 0.86; P = .054, respectively). Weekly paclitaxel improved DFS and OS (HR, 0.69; P = .010 and HR, 0.69; P = .019, respectively) in triple-negative breast cancer. For hormone receptor-positive, human epidermal growth factor receptor 2-nonoverexpressing disease, no experimental arm improved OS, and black race and obesity were associated with increased risk of breast cancer recurrence and death.

CONCLUSION:

Improved outcomes initially observed for weekly paclitaxel were qualitatively similar but quantitatively less pronounced with longer follow-up, although exploratory analysis suggested substantial benefit in triple-negative disease. Further research is required to understand why obesity and race influence clinical outcome in hormone receptor-positive disease.

• Authors: Joseph A Sparano, Fengmin Zhao, Silvana Martino, Jennifer A Ligibel, Edith A Perez, Tom Saphner, Antonio C Wolff, George W Sledge Jr, William C Wood, Nancy E Davidson
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 33 Issue 21 Pg. 2353-60 (Jul 20 2015) ISSN: 1527-7755 [Electronic] United States
• PMID: 26077235 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
• Copyright: © 2015 by American Society of Clinical Oncology.

Chemical References

• Taxoids
• Docetaxel
• Doxorubicin
• Cyclophosphamide
• Paclitaxel

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Breast Neoplasms (drug therapy, ethnology, pathology, surgery)
• Cyclophosphamide (administration & dosage)
• Disease-Free Survival
• Docetaxel
• Doxorubicin (administration & dosage)
• Drug Administration Schedule
• Female
• Follow-Up Studies
• Humans
• Longitudinal Studies
• Middle Aged
• Neoplasm Staging
• Obesity (complications, ethnology)
• Paclitaxel (administration & dosage)
• Taxoids (administration & dosage)