Overall survival benefit for sequential doxorubicin-docetaxel compared with concurrent doxorubicin and docetaxel in node-positive breast cancer-8-year results of the breast international group 02-98 phase III trial

C. Oakman, P. A. Francis, J. Crown, E. Quinaux, M. Buyse, E. De azambuja, M. Margeli vila, M. Andersson, B. Nordenskjöld, R. Jakesz, B. Thürlimann, J. Gutiérrez, V. Harvey, L. Punzalan, P. Dell'Orto, D. Larsimont, I. Steinberg, R. D. Gelber, M. Piccart-Gebhart, G. VialeA. Di Leo

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Abstract

Background: In women with node-positive breast cancer, the Breast International Group (BIG) 02-98 tested the incorporation of docetaxel (Taxotere) into doxorubicin (Adriamycin)-based chemotherapy, and compared sequential and concurrent docetaxel. At 5 years, there was a trend for improved disease-free survival (DFS) with docetaxel. We present results at 8-year median follow-up and exploratory analyses within biologically defined subtypes. Methods: Patients were randomly assigned to one of four treatments: (i) sequential control: doxorubicin (A) (75 mg/m. 2) × 4 → classical cyclophosphamide, methotrexate, 5-fluorouracil (CMF); (ii) concurrent control: doxorubicin, cyclophosphamide (AC)(60/600 mg/m. 2) × 4 →CMF; (iii) sequential docetaxel: A (75 mg/m. 2) × 3 → docetaxel (T) (100 mg/m. 2) × 3 → CMF and (iv) concurrent docetaxel: AT(50/75 mg/m. 2) × 4 →CMF. The primary comparison evaluated docetaxel efficacy regardless of the schedule. Exploratory analyses were undertaken within biologically defined subtypes. Results: Two thousand eight hundred and eighty-seven patients were enrolled. After 93.4 months of median follow-up, there were 916 DFS events. For the primary comparison, there was no significant improvement in DFS from docetaxel [hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.80-1.05, P = 0.187]. In secondary comparisons, sequential docetaxel significantly improved DFS compared with sequential control (HR = 0.81, 95% CI = 0.67-0.99, P = 0.036), and significantly improved DFS (HR = 0.84, 95% CI = 0.72-0.99, P = 0.035) and overall survival (OS) (HR = 0.79, 95% CI = 0.65-0.98, P = 0.028) compared with concurrent doxorubicin-docetaxel. Luminal-A disease had the best prognosis. HRs favored addition of sequential docetaxel in all subtypes, except luminal-A; but this observation was not statistically supported because of limited numbers. Conclusion: With further follow-up, the sequential docetaxel schedule resulted in significantly better OS than concurrent doxorubicin-docetaxel, and continued to show better DFS than sequential doxorubicin-based control.

Original languageEnglish
Article numbermds627
Pages (from-to)1203-1211
Number of pages9
JournalAnnals of Oncology
Volume24
Issue number5
DOIs
Publication statusPublished - May 2013

Keywords

  • Adjuvant
  • Breast cancer
  • Chemotherapy
  • Docetaxel
  • Doxorubicin
  • Sequential

ASJC Scopus subject areas

  • Oncology
  • Hematology

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    Oakman, C., Francis, P. A., Crown, J., Quinaux, E., Buyse, M., De azambuja, E., vila, M. M., Andersson, M., Nordenskjöld, B., Jakesz, R., Thürlimann, B., Gutiérrez, J., Harvey, V., Punzalan, L., Dell'Orto, P., Larsimont, D., Steinberg, I., Gelber, R. D., Piccart-Gebhart, M., ... Di Leo, A. (2013). Overall survival benefit for sequential doxorubicin-docetaxel compared with concurrent doxorubicin and docetaxel in node-positive breast cancer-8-year results of the breast international group 02-98 phase III trial. Annals of Oncology, 24(5), 1203-1211. [mds627]. https://doi.org/10.1093/annonc/mds627