Ten-year results of intense dose-dense chemotherapy show superior survival compared with a conventional schedule in high-risk primary breast cancer: final results of AGO phase III iddEPC trial

Background: Primary breast cancer patients with extensive axillary lymph-node involvement have a limited prognosis. The AGO (Arbeitsgemeinschaft fuer Gynaekologische Onkologie) trial compared intense dose-dense adjuvant chemotherapy with conventionally scheduled chemotherapy in high-risk breast cancer patients. Here we report the final, 10-year follow-up analysis. Patients and methods: Enrolment took place between December 1998 until April 2003. 1284 patients with four or more involved axillary lymph nodes were randomly assigned to receive three courses each of intense dose-dense sequential epirubicin, paclitaxel and cyclophosphamide (iddEPC) q2w or standard epirubicin/cyclophosphamide followed by paclitaxel (ECcP) q3w. Event-free survival (EFS) was the primary endpoint. Results: 658 patients were assigned to receive iddEPC and 626 patients were assigned to receive ECcP. The median duration of follow-up was 122 months. EFS was 47% (95% CI 43%-52%) in the standard group and 56% (95% CI 52%-60%) in the iddEPC group (hazard ratio [HR] 0.74, 95% CI 0.63-0.87; log-rank P=0.00014, one sided). This benefit was independent of menopausal, hormone receptor or HER2 status. 10-year overall survival (OS) was 59% (95% CI 55%-63%) for patients in the standard group and 69% (95% CI 65%-73%) for patients in the iddEPC group (HR = 0.72, 95% CI 0.60-0.87; log-rank P=0.0007, two sided). Nine vs. two cases of secondary myeloid leukaemia/MDS were observed in the iddEPC and the ECcP arm, respectively. Conclusion: The previously reported OS benefit of intense dose-dense EPC in comparison to conventionally dosed ECcP has been further increased and achieved an absolute difference of 10% after 10 years of follow-up.