Long-term follow-up of the E1199 phase III trial evaluating the role of taxane and schedule in operable breast cancer

Joseph A. Sparano, Fengmin Zhao, Silvana Martino, Jennifer A. Ligibel, Edith A. Perez, Tom Saphner, Antonio C. Wolff, George W. Sledge, William C. Wood, Nancy E. Davidson

Research output: Contribution to journalArticle

70 Citations (Scopus)

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 x 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.

Original languageEnglish (US)
Pages (from-to)2353-2360
Number of pages8
JournalJournal of Clinical Oncology
Volume33
Issue number21
DOIs
StatePublished - Jul 20 2015

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Paclitaxel
docetaxel
Appointments and Schedules
Breast Neoplasms
Disease-Free Survival
Obesity
Survival
Hormones
Triple Negative Breast Neoplasms
Proportional Hazards Models
Doxorubicin
Cyclophosphamide
taxane
Clinical Trials
Recurrence
Research

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Long-term follow-up of the E1199 phase III trial evaluating the role of taxane and schedule in operable breast cancer. / Sparano, Joseph A.; Zhao, Fengmin; Martino, Silvana; Ligibel, Jennifer A.; Perez, Edith A.; Saphner, Tom; Wolff, Antonio C.; Sledge, George W.; Wood, William C.; Davidson, Nancy E.

In: Journal of Clinical Oncology, Vol. 33, No. 21, 20.07.2015, p. 2353-2360.

Research output: Contribution to journalArticle

Sparano, JA, Zhao, F, Martino, S, Ligibel, JA, Perez, EA, Saphner, T, Wolff, AC, Sledge, GW, Wood, WC & Davidson, NE 2015, 'Long-term follow-up of the E1199 phase III trial evaluating the role of taxane and schedule in operable breast cancer', Journal of Clinical Oncology, vol. 33, no. 21, pp. 2353-2360. https://doi.org/10.1200/JCO.2015.60.9271
Sparano, Joseph A. ; Zhao, Fengmin ; Martino, Silvana ; Ligibel, Jennifer A. ; Perez, Edith A. ; Saphner, Tom ; Wolff, Antonio C. ; Sledge, George W. ; Wood, William C. ; Davidson, Nancy E. / Long-term follow-up of the E1199 phase III trial evaluating the role of taxane and schedule in operable breast cancer. In: Journal of Clinical Oncology. 2015 ; Vol. 33, No. 21. pp. 2353-2360.
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AU - Sparano, Joseph A.

AU - Zhao, Fengmin

AU - Martino, Silvana

AU - Ligibel, Jennifer A.

AU - Perez, Edith A.

AU - Saphner, Tom

AU - Wolff, Antonio C.

AU - Sledge, George W.

AU - Wood, William C.

AU - Davidson, Nancy E.

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Y1 - 2015/7/20

N2 - 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 x 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.

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