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

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/m) every 2 weeks followed by 3 cycles of paclitaxel (T, 200 mg/m) 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/m (Arm B, E-CMF-wD) or nine consecutive weekly cycles of paclitaxel (wT) 80 mg/m (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.