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
In: Clinical cancer research : an official journal of the American Association for Cancer Research, Jg. 28 (2022-02-13), Heft 22
Online
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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
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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
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Autor/in / Beteiligte Person: | Oleg, Gluz ; Ulrike, Nitz ; Cornelia, Kolberg-Liedtke ; Aleix, Prat ; Matthias, Christgen ; Sherko, Kuemmel ; Mohammad Parsa, Mohammadian ; Daniel, Gebauer ; Ronald, Kates ; Laia, Paré ; Eva-Maria, Grischke ; Helmut, Forstbauer ; Michael, Braun ; Mathias, Warm ; John, Hackmann ; Christoph, Uleer ; Bahriye, Aktas ; Claudia, Schumacher ; Rachel, Wuerstlein ; Monika, Graeser ; Enrico, Pelz ; Katarzyna, Jóźwiak ; Christine, Zu Eulenburg ; Hans Heinrich, Kreipe ; Nadia, Harbeck |
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Zeitschrift: | Clinical cancer research : an official journal of the American Association for Cancer Research, Jg. 28 (2022-02-13), Heft 22 |
Veröffentlichung: | 2022 |
Medientyp: | unknown |
ISSN: | 1557-3265 (print) |
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