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

TY - JOUR

T1 - 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

AU - Möbus, V

AU - Jackisch, C

AU - Lück, H J

AU - du Bois, A

AU - Thomssen, C

AU - Kuhn, W

AU - Nitz, U

AU - Schneeweiss, A

AU - Huober, J

AU - Harbeck, N

AU - von Minckwitz, G

AU - Runnebaum, I B

AU - Hinke, A

AU - Konecny, G E

AU - Untch, M

AU - Kurbacher, C

AU - AGO Breast Study Group (AGO-B)

AU - Müller , Volkmar

N1 - © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: Primary breast cancer (BC) patients with extensive axillary lymph-node involvement have a limited prognosis. The Arbeitsgemeinschaft fuer Gynaekologische Onkologie (AGO) trial compared intense dose-dense (idd) adjuvant chemotherapy with conventionally scheduled chemotherapy in high-risk BC patients. Here we report the final, 10-year follow-up analysis.Patients and methods: Enrolment took place between December 1998 and April 2003. A total of 1284 patients with 4 or more involved axillary lymph nodes were randomly assigned to receive 3 courses each of idd sequential epirubicin, paclitaxel and cyclophosphamide (iddEPC) q2w or standard epirubicin/cyclophosphamide followed by paclitaxel (EC → P) q3w. Event-free survival (EFS) was the primary end point.Results: A total of 658 patients were assigned to receive iddEPC and 626 patients were assigned to receive EC → P. The median duration of follow-up was 122 months. EFS was 47% (95% CI 43% to 52%) in the standard group and 56% (95% CI 52% to 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. Ten-year overall survival (OS) was 59% (95% CI 55% to 63%) for patients in the standard group and 69% (95% CI 65% to 73%) for patients in the iddEPC group (HR = 0.72, 95% CI 0.60-0.87; log-rank P = 0.0007, two-sided). Nine versus two cases of secondary myeloid leukemia/myelodysplastic syndrome were observed in the iddEPC and the EC → P arm, respectively.Conclusion: The previously reported OS benefit of iddEPC in comparison to conventionally dosed EC → P has been further increased and achieved an absolute difference of 10% after 10 years of follow-up.

AB - Background: Primary breast cancer (BC) patients with extensive axillary lymph-node involvement have a limited prognosis. The Arbeitsgemeinschaft fuer Gynaekologische Onkologie (AGO) trial compared intense dose-dense (idd) adjuvant chemotherapy with conventionally scheduled chemotherapy in high-risk BC patients. Here we report the final, 10-year follow-up analysis.Patients and methods: Enrolment took place between December 1998 and April 2003. A total of 1284 patients with 4 or more involved axillary lymph nodes were randomly assigned to receive 3 courses each of idd sequential epirubicin, paclitaxel and cyclophosphamide (iddEPC) q2w or standard epirubicin/cyclophosphamide followed by paclitaxel (EC → P) q3w. Event-free survival (EFS) was the primary end point.Results: A total of 658 patients were assigned to receive iddEPC and 626 patients were assigned to receive EC → P. The median duration of follow-up was 122 months. EFS was 47% (95% CI 43% to 52%) in the standard group and 56% (95% CI 52% to 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. Ten-year overall survival (OS) was 59% (95% CI 55% to 63%) for patients in the standard group and 69% (95% CI 65% to 73%) for patients in the iddEPC group (HR = 0.72, 95% CI 0.60-0.87; log-rank P = 0.0007, two-sided). Nine versus two cases of secondary myeloid leukemia/myelodysplastic syndrome were observed in the iddEPC and the EC → P arm, respectively.Conclusion: The previously reported OS benefit of iddEPC in comparison to conventionally dosed EC → P has been further increased and achieved an absolute difference of 10% after 10 years of follow-up.

KW - Journal Article

U2 - 10.1093/annonc/mdx690

DO - 10.1093/annonc/mdx690

M3 - SCORING: Journal article

C2 - 29069370

VL - 29

SP - 178

EP - 185

JO - ANN ONCOL

JF - ANN ONCOL

SN - 0923-7534

IS - 1

ER -