Long-term safety and survival outcomes from the Scandinavian Breast Group 2004-1 randomized phase II trial of tailored dose-dense adjuvant chemotherapy for early breast cancer

Alexios Matikas,Elisabet Lidbrink,Per Edlund,Sara Margolin,Mats Hellström,Hemming Johansson,Barbro Linderholm,Per Malmstrom,Nils-Olof Bengtsson,Per Karlsson,Theodoros Foukakis,Henrik Lindman,Lena Karlsson,Jonas Bergh,Kenneth Villman

doi:10.1007/s10549-017-4599-4

Abstract

PurposeAlthough adjuvant polychemotherapy improves outcomes for early breast cancer, the significant variability in terms of pharmacokinetics results in differences in efficacy and both short and long-term toxicities. Retrospective studies support the use of dose tailoring according to the hematologic nadirs.MethodsThe SBG 2004-1 trial was a randomized feasibility phase II study which assessed tailored dose-dense epirubicin and cyclophosphamide (EC) followed by docetaxel (T) (group A), the same regimen with fixed doses (group B) and the TAC regimen (group C). Women aged 18–65 years, ECOG PS 0-1 with at least one positive axillary lymph node were randomized 1:1:1. The primary endpoint of the study was the safety and feasibility of the treatment. Toxicity was graded according to CTC-AE version 3.0. The design and short-term toxicity have been previously published. Here, we report safety and efficacy data after 10 years of follow-up.ResultsA total of 124 patients were included in the study. After a median follow-up of 10.3 years, the probability for 10-year survival was 78.5, 75.1, and 63.4% and for relapse free survival 64.1, 71.0, and 59.5% for groups A, B, and C, respectively. There were no cases of clinically diagnosed cardiotoxicity or hematologic malignancies. No patient was lost to follow-up.ConclusionsIn this randomized phase II trial, tailored dose adjuvant chemotherapy was feasible, without an increased risk for long-term adverse events after a median follow-up of 10 years.

Highlights

The administration of adjuvant polychemotherapy (ACT) after surgery for early and locally advanced breast cancer (BC) has been consistently shown to decrease both breast cancer-specific and overall mortality [1]
A trial-level meta-analysis concluded that only patients with estrogen receptor (ER) negative disease had a significantly improved overall survival benefit from DD-CT [11], the findings of individual randomized trials [7, 10] reveal a significant benefit in DFS for both ER-positive and ER-negative disease
Since efficacy endpoints were not predefined for the feasibility phase II part of the study, for the scope of this analysis, we performed an exploratory efficacy analysis using the endpoints of the continuation phase III part

Summary

Introduction

The administration of adjuvant polychemotherapy (ACT) after surgery for early and locally advanced breast cancer (BC) has been consistently shown to decrease both breast cancer-specific and overall mortality [1]. Breast Cancer Research and Treatment (2018) 168:349–355 have been undertaken in order to improve the concurrent or sequential administration of an anthracycline and taxane, including either the escalation of administered doses (dose intense chemotherapy) or the administration of conventional doses in shorter time intervals (dose-dense chemotherapy, DD-CT). A trial-level meta-analysis concluded that only patients with estrogen receptor (ER) negative disease had a significantly improved overall survival benefit from DD-CT [11], the findings of individual randomized trials [7, 10] reveal a significant benefit in DFS for both ER-positive and ER-negative disease. The Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) meta-analysis reported similar proportional reductions in risk of death induced by ACT regardless of ER status; the same relative reduction was found to be independent of age, tumor size, axillary lymph node status, and use of tamoxifen [1]

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Results

Conclusion