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Data from De-escalated Neoadjuvant Chemotherapy in Early Triple-Negative Breast Cancer (TNBC): Impact of Molecular Markers and Final Survival Analysis of the WSG-ADAPT-TN Trial

Authors :
Nadia Harbeck
Hans Heinrich Kreipe
Christine zu Eulenburg
Katarzyna Jóźwiak
Enrico Pelz
Monika Graeser
Rachel Wuerstlein
Claudia Schumacher
Bahriye Aktas
Christoph Uleer
John Hackmann
Mathias Warm
Michael Braun
Helmut Forstbauer
Eva-Maria Grischke
Laia Paré
Ronald Kates
Daniel Gebauer
Mohammad Parsa Mohammadian
Sherko Kuemmel
Matthias Christgen
Aleix Prat
Cornelia Kolberg-Liedtke
Ulrike Nitz
Oleg Gluz
Publication Year :
2023
Publisher :
American Association for Cancer Research (AACR), 2023.

Abstract

Purpose:Although optimal treatment in early triple-negative breast cancer (TNBC) remains unclear, de-escalated chemotherapy appears to be an option in selected patients within this aggressive subtype. Previous studies have identified several pro-immune factors as prognostic markers in TNBC, but their predictive impact regarding different chemotherapy strategies is still controversial.Experimental Design:ADAPT-TN is a randomized neoadjuvant multicenter phase II trial in early patients with TNBC (n = 336) who were randomized to 12 weeks of nab-paclitaxel 125 mg/m2 + gemcitabine or carboplatin d 1,8 q3w. Omission of further (neo-) adjuvant chemotherapy was allowed only in patients with pathological complete response [pCR, primary endpoint (ypT0/is, ypN0)]. Secondary invasive/distant disease-free and overall survival (i/dDFS, OS) and translational research objectives included quantification of a predictive impact of markers regarding selection for chemotherapy de-escalation, measured by gene expression of 119 genes (including PAM50 subtype) by nCounter platform and stromal tumor-infiltrating lymphocytes (sTIL).Results:After 60 months of median follow-up, 12-week-pCR was favorably associated (HR, 0.24; P = 0.001) with 5y-iDFS of 90.6% versus 62.8%. No survival advantage of carboplatin use was observed, despite a higher pCR rate [HR, 1.04; 95% confidence interval (CI), 0.68–1.59]. Additional anthracycline-containing chemotherapy was not associated with a significant iDFS advantage in pCR patients (HR, 1.29; 95% CI, 0.41–4.02). Beyond pCR rate, nodal status and high sTILs were independently associated with better iDFS, dDFS, and OS by multivariable analysis.Conclusions:Short de-escalated neoadjuvant taxane/platinum-based combination therapy appears to be a promising strategy in early TNBC for using pCR rate as an early decision point for further therapy (de-) escalation together with node-negative status and high sTILs.See related commentary by Sharma, p. 4840

Details

ISSN :
10780432
Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....7beb568b022ee30ffa8db4063d737ea4
Full Text :
https://doi.org/10.1158/1078-0432.c.6532775