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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18 Citations (Scopus)

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
Pages (from-to)1203-11
Number of pages9
JournalAnnals of Oncology
Volume24
Issue number5
DOIs
Publication statusPublished - May 2013

Keywords

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents/administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols/administration & dosage
  • Breast Neoplasms/drug therapy
  • Cyclophosphamide/administration & dosage
  • Disease-Free Survival
  • Docetaxel
  • Doxorubicin/administration & dosage
  • Drug Administration Schedule
  • Female
  • Fluorouracil/administration & dosage
  • Humans
  • Lymphatic Metastasis
  • Methotrexate/administration & dosage
  • Middle Aged
  • Taxoids/administration & dosage
  • Young Adult

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