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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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. / Gluz, Oleg; Nitz, Ulrike; Kolberg-Liedtke, Cornelia; Prat, Aleix; Christgen, Matthias; Kuemmel, Sherko; Mohammadian, Mohammad Parsa; Gebauer, Daniel; Kates, Ronald; Paré, Laia; Grischke, Eva-Maria; Forstbauer, Helmut; Braun, Michael; Warm, Mathias; Hackmann, John; Uleer, Christoph; Aktas, Bahriye; Schumacher, Claudia; Wuerstlein, Rachel; Graeser, Monika; Pelz, Enrico; Jóźwiak, Katarzyna; Zu Eulenburg, Christine; Kreipe, Hans Heinrich; Harbeck, Nadia; ADAPT TN investigators.
In: CLIN CANCER RES, Vol. 28, No. 22, 14.11.2022, p. 4995-5003.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - 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
AU - Gluz, Oleg
AU - Nitz, Ulrike
AU - Kolberg-Liedtke, Cornelia
AU - Prat, Aleix
AU - Christgen, Matthias
AU - Kuemmel, Sherko
AU - Mohammadian, Mohammad Parsa
AU - Gebauer, Daniel
AU - Kates, Ronald
AU - Paré, Laia
AU - Grischke, Eva-Maria
AU - Forstbauer, Helmut
AU - Braun, Michael
AU - Warm, Mathias
AU - Hackmann, John
AU - Uleer, Christoph
AU - Aktas, Bahriye
AU - Schumacher, Claudia
AU - Wuerstlein, Rachel
AU - Graeser, Monika
AU - Pelz, Enrico
AU - Jóźwiak, Katarzyna
AU - Zu Eulenburg, Christine
AU - Kreipe, Hans Heinrich
AU - Harbeck, Nadia
AU - ADAPT TN investigators
N1 - ©2022 American Association for Cancer Research.
PY - 2022/11/14
Y1 - 2022/11/14
N2 - 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.
AB - 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.
KW - Humans
KW - Triple Negative Breast Neoplasms/drug therapy
KW - Neoadjuvant Therapy/adverse effects
KW - Carboplatin/administration & dosage
KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects
KW - Survival Analysis
U2 - 10.1158/1078-0432.CCR-22-0482
DO - 10.1158/1078-0432.CCR-22-0482
M3 - SCORING: Journal article
C2 - 35797219
VL - 28
SP - 4995
EP - 5003
JO - CLIN CANCER RES
JF - CLIN CANCER RES
SN - 1078-0432
IS - 22
ER -