257O - Intense dose-dense epirubicin (E), paclitaxel (T), cyclophosphamide (C) (iddETC) is highly effective in adjuvant therapy of node-positive breast ca...

Date 29 September 2014
Event ESMO 2014
Session Breast cancer, early stage
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Early Stage
Pharmacology
Presenter Christoph Thomssen
Citation Annals of Oncology (2014) 25 (suppl_4): iv85-iv109. 10.1093/annonc/mdu327
Authors C. Thomssen1, G. von Minckwitz2, C. Jackisch3, H.J. Lueck4, A. Schneeweiss5, H. Tesch6, D. Elling7, N. Harbeck8, B. Conrad9, T. Fehm10, J. Huober11, V. Müller12, I. Bauerfeind13, S. Loibl14, V. Nekljudova15, M. Untch16, V. Moebus17
  • 1Departement Of Gynecology, Martin-Luther-University Halle-Wittenberg, 06120 - Halle (Saale)/DE
  • 2Managing Director, GBG Forschungs GmbH, 63263 - Neu-Isenburg/DE
  • 3Oncology, Klinikum Offenbach GmbH, Offenbach/DE
  • 4Gynecological Oncology, Praxis, Hannover/DE
  • 5University Hospital, National Center for Tumor Diseases, Heidelberg/DE
  • 6Clinic Of Gynecology, Bethanien Hospital, DE-60389 - Frankfurt am Main/DE
  • 7Clinic Of Gynecology, Sana Klinikum Lichtenberg, berlin/DE
  • 8Clinic Of Gynecology, Ludwig-Maximilian University Muinch, München/DE
  • 9Clinic Of Gynecology, Elisabeth Hospital, Kassel/DE
  • 10Clinic Of Gynecology, Heinrich-Heine University Duesseldorf, Duesseldorf/DE
  • 11Clinic Of Gynecology, University Ulm, Ulm/DE
  • 12Department Of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg/DE
  • 13Clinic Of Gynecology, Klinikum Landshut, Landshut/DE
  • 14Medicine And Research, German Breast Group (GBG) Forschungs GmbH, Neu-Isenburg/DE
  • 15Medicine And Research, GBG Forschungs GmbH, Neu-Isenburg/DE
  • 16Chefarzt Der Frauenklinik, HELIOS Klinikum Berlin-Buch, 13125 - Berlin/DE
  • 17Departement Of Gynecology, Klinikum Frankfurt Hoechst, Frankfurt/DE

Abstract

Aim

In locally advanced breast cancer pts (≥pN2), adjuvant iddETC resulted in superior disease-free (DFS) and overall survival (OS) compared to conventionally dosed EC > Tq3w (AGO-ETC; Möbus JCO 2010). In the GAIN trial, iddETC was compared to a 4-drug dose-dense regimen with capecitabine (ddEC > TwX). Using the GAIN data, here we want to confirm the iddETC-results of the AGO-ETC trial with regard to DFS, OS, and toxicity.

Methods

In the AGO-ETC trial (1998-2003) 681 of 1,284, and in GAIN (2004-2008) 1,498 of 3,023 pts were treated with iddETC. Pts were included in AGO-ETC if ≥pN2 and in GAIN if ≥pN1; median number of positive nodes was 8 and 5, respectively; all other inclusion criteria were comparable. Median follow-up was 62 and 74 months, respectively, in both trials primary end point was DFS. IddETC consists of a sequence of 3 x E 150mg/m2, 3 x T 225 mg/m2, and 3 x C 2,5 g/m2 q2w, with primary G-CSF support. After 40% accrual in GAIN, a reduced dose of C (2,0 g/m2) and antibiotic prophylaxis was implemented. Pts were randomly assigned to anemia prophylaxis with ESF in AGO-ETC, and to adjuvant ibandronate in GAIN (von Minckwitz JCO 2013).

Results

In the iddETC-arm of AGO-ETC, 5y-DFS was 70% (95% CI 68% - 75%) and 5y-OS was 82% (95% CI, 79%to 85%). Comparing to conventional EC > Tq3w, HR for DFS was 0.69 (95% CI, 0.57 - 0.84). In GAIN, 5y-DFS was 80% (95% CI 78% - 82%) and 5y-OS was 85%. DdEC > TwX was not superior to iddETC. Evaluating GAIN pts with ≥pN2 (n = 923) separately, in order to match with the AGO-ETC inclusion criteria, results were comparable: 5yr-DFS was 75% (95% CI 72% - 78%) and 5y-OS was 85% (95% CI 83% - 88%). In AGO-ETC, 47 pts (7%) had at least one episode of febrile neutropenia during iddETC, no toxic death was observed. In GAIN, three pts (0,2%) died from therapy related septicaemia during iddETC. In both trials, paclitaxel induced neuropathy was in the expected range, and no grade 3 congestive heart failure occurred. Treatment induced MDS/AML was rare in both, AGO-ETC (0,6%) and GAIN (0,3%).

Conclusions

We consistently show high efficacy of adjuvant iddETC for node-positive breast cancer pts (≥pN2) in two consecutive prospective trials: DFS and OS-results were superior to those with conventionally dosed therapy. In the reported studies, iddETC was feasible without excessive toxicity. We suggest to add iddETC to the group of preferred regimens in current guidelines.

Disclosure

C. Thomssen: has received compensated honoraria for presentations and participating in advisory boards from Roche, Amgen, Pfizer; G. von Minckwitz: has received research funds from Roche, BMS, Amgen, Speaker and consultancy honoraria from Roche and Amgen; H. Tesch: has received compensated honoraria from Roche; N. Harbeck has received compensated honoraria from Roche; V. Müller: has received speaker honoraria from Amgen, Celgene, Glaxo Smith Kline, Pierre-Fabre, Roche, Jannsen-Cilag I. Bauerfeind: speakers honoraria from Amgen and Bristol Myers Squibb; S. Loibl: has received compensated honoraria for presentations and participating in advisory boards from Roche, Amgen V. Moebus: has receivedCompensated honoraria from Amgen, Jannsen-Cilag, Roche for presentations and participation in advisory boards. All other authors have declared no conflicts of interest.