Universität zu Köln

Gluz, Oleg, Nitz, Ulrike, Liedtke, Cornelia, Christgen, Matthias, Grischke, Eva-Maria, Forstbauer, Helmut, Braun, Michael, Warm, Mathias, Hackmann, John, Uleer, Christoph, Aktas, Bahriye, Schumacher, Claudia, Bangemann, Nikola, Lindner, Christoph, Kuemmel, Sherko, Clemens, Michael, Potenberg, Jochem, Staib, Peter, Kohls, Andreas, von Schumann, Raquel and Harbeck, Nadia (2018). Comparison of Neoadjuvant Nab-Paclitaxe plus Carboplatin vs Nab-Paclitaxe plus Gemcitabine in Triple-Negative Breast Cancer: Randomized WSG-ADAPT-TN Trial Results. JNCI-J. Natl. Cancer Inst., 110 (6). S. 628 - 638. CARY: OXFORD UNIV PRESS INC. ISSN 1460-2105

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Abstract

Background: Pathological complete response (pCR) is associated with improved prognosis in triple-negative breast cancer (TNBC). The optimal chemotherapy regimen is unclear. Weekly nab-paclitaxel vs conventional paclitaxel or addition of carboplatin to anthracycline-taxane results in higher pCR rates with uncertain survival impact. We evaluated carboplatin vs gemcitabine with a nab-paclitaxel backbone as a short 12-week A-free regimen with a focus on early response. Methods: Patients with TNBC (estrogen receptor/progesterone receptor < 1%, human epidermal growth factor receptor 2-negative, cT1c-cT4c, cN0/+) were randomly assigned to A: nab-paclitaxel 125 mg/m(2)/gemcitabine 1000 mg/m(2) d1,8 three times weekly (q3w); vs B: nab-paclitaxel 125 mg/m(2)/carboplatin AUC2 day 1,8 q3w. The trial was powered for a pCR (ypT0/is ypN0) comparison by therapy arm and early response (defined as Ki-67 decrease >30% or < 500 invasive tumor cells in the three-week serial biopsy). All statistical tests were two-sided. Results: A total of 336 patients were enrolled (48 centers, arms A/B: n = 182/154). The median age was 50 years. At baseline (A vs B), 62.6% and 62.9% had cT2-4c tumors; 86.8% and 90.9% completed therapy per protocol, respectively. pCR favored arm B (28.7%, 95% CI = 0.22 to 0.36, vs 45.9%, 95% CI = 0.38 to 0.54; 95% CI(d(BA)) = 6.2% to 27.9%, P = .002) and was lower in nonresponders than in early responders (19.5% vs 44.4%, P < .001) or in patients with unclassifiable early response (50.0%). The nab-paclitaxel/gemcitabine was associated with more frequent dose reductions (20.6% vs 11.9%, P = .04), treatment-related serious adverse events (11.1% vs 5.3%, P = .07), grade 3-4 infections (7.2% vs 2.6%, P = .07), and grade 3-4 ALAT elevations (11.7 vs 3.3%, P = .01). Conclusions: This first large randomized trial suggests high efficacy and excellent tolerability of a neoadjuvant nabpaclitaxel/carboplatin regimen, superior to nab-paclitaxel/gemcitabine in TNBC. De-escalation of further chemotherapy in patients with early pCR after a short anthracycline-free regimen is a promising field of future research. Early necrotic morphological changes and/or proliferation decrease after the first therapy cycle seem to be associated with subsequent pCR.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gluz, Oleg UNSPECIFIED UNSPECIFIED UNSPECIFIED Nitz, Ulrike UNSPECIFIED UNSPECIFIED UNSPECIFIED Liedtke, Cornelia UNSPECIFIED UNSPECIFIED UNSPECIFIED Christgen, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Grischke, Eva-Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Forstbauer, Helmut UNSPECIFIED UNSPECIFIED UNSPECIFIED Braun, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Warm, Mathias UNSPECIFIED UNSPECIFIED UNSPECIFIED Hackmann, John UNSPECIFIED UNSPECIFIED UNSPECIFIED Uleer, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Aktas, Bahriye UNSPECIFIED UNSPECIFIED UNSPECIFIED Schumacher, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Bangemann, Nikola UNSPECIFIED UNSPECIFIED UNSPECIFIED Lindner, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuemmel, Sherko UNSPECIFIED UNSPECIFIED UNSPECIFIED Clemens, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Potenberg, Jochem UNSPECIFIED UNSPECIFIED UNSPECIFIED Staib, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Kohls, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED von Schumann, Raquel UNSPECIFIED UNSPECIFIED UNSPECIFIED Harbeck, Nadia UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-183399
DOI:	10.1093/jnci/djx258
Journal or Publication Title:	JNCI-J. Natl. Cancer Inst.
Volume:	110
Number:	6
Page Range:	S. 628 - 638
Date:	2018
Publisher:	OXFORD UNIV PRESS INC
Place of Publication:	CARY
ISSN:	1460-2105
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PATHOLOGICAL COMPLETE RESPONSE; PHASE-III TRIAL; OPEN-LABEL; 1ST-LINE THERAPY; FREE SURVIVAL; CHEMOTHERAPY; RISK; CYCLOPHOSPHAMIDE; WOMEN; BEVACIZUMAB Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/18339