Dose-dense sequential adjuvant chemotherapy in the trastuzumab era: final long-term results of the Hellenic Cooperative Oncology Group Phase III HE10/05 Trial

Br J Cancer. 2022 Sep;127(4):695-703. doi: 10.1038/s41416-022-01846-y. Epub 2022 May 24.

Abstract

Background: Dose-dense sequential chemotherapy with anthracyclines and taxanes achieved an 18% reduction of recurrence risk in early breast cancer (BC). The optimal chemotherapy schedule and interval between cycles remain under investigation.

Methods: Overall, 990 patients were randomised to receive either three cycles of epirubicin (E, 110 mg/m2) every 2 weeks followed by 3 cycles of paclitaxel (T, 200 mg/m2) every 2 weeks followed by three cycles of intensified CMF (Control Arm A, E-T-CMF) that was previously used in BC or three cycles of epirubicin followed by three cycles of CMF followed by nine consecutive weekly cycles of docetaxel (wD) 35 mg/m2 (Arm B, E-CMF-wD) or nine consecutive weekly cycles of paclitaxel (wT) 80 mg/m2 (Arm C, E-CMF-wT). Trastuzumab was administered for HER2-positive disease.

Results: At a median follow-up of 13.3 years, 330 disease-free survival (DFS) events (33.3%) were reported. DFS and overall survival (OS) did not differ between patients in the combined B and C arms versus arm A either in the entire cohort (HR = 0.90, P = 0.38 and HR = 0.85, P = 0.20) or among trastuzumab-treated patients (HR = 0.69, P = 0.13 and HR = 0.67, P = 0.13). Thirty-four patients (3.4%) developed secondary neoplasms.

Conclusions: Overall, no significant differences in survival were found amongst the studied regimens after a long-term observational period.

Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12610000151033.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Australia
  • Breast Neoplasms*
  • Chemotherapy, Adjuvant
  • Cyclophosphamide / adverse effects
  • Disease-Free Survival
  • Epirubicin / adverse effects
  • Female
  • Fluorouracil / adverse effects
  • Humans
  • Paclitaxel / adverse effects
  • Trastuzumab / adverse effects

Substances

  • Epirubicin
  • Cyclophosphamide
  • Trastuzumab
  • Paclitaxel
  • Fluorouracil

Associated data

  • ANZCTR/ACTRN12610000151033