Abstract P1-13-01: Comparison of 12 weeks neoadjuvant Nab-paclitaxel combined with carboplatinum vs. gemcitabine in triple- negative breast cancer: WSG-ADAPT TN randomized phase II trial
Authors: Gluz O , Nitz U , Liedtke C , Christgen M , Sotlar K , Grischke EM , Forstbauer H , Braun M , Warm M , Hackmann J , Uleer C , Aktas B , Schumacher C , Bangemann N , Lindner C , Kuemmel S , Clemens M , Potenberg J , Staib P , Kohls A , Pelz E , Kates RE , Wuerstlein R , Kreipe HH , Harbeck N 
Published: May 2016

Abstract
Background: Pathological complete response (pCR) is associated with improved prognosis in TNBC, but optimal chemotherapy remains unclear. Use of weekly nab- paclitaxel (Nab-Pac) vs. conventional paclitaxel and also addition of carboplatinum(Carbo) to anthracycline-taxane(A/T) containing chemotherapy results in significantly higher pCR rates in TNBC with unclear impact on survival and increased toxicity.
The ADAPT study seeks to compare Carbo vs. gemcitabine(Gem) added to nab- paclitaxel as a short 12-week A-free regimen. It also assesses efficacy in early responders vs. non-responders by 3-week proliferation and/or imaging response.
Methods: ADAPT TN compares 12-week neoadjuvant regimens: Carbo vs. Gem combined with Nab-Pac and aims to identify early-response markers for pCR (yPN0 and ypT0/is). TNBC patients (centrally confirmed ER/PR &lt;1%, HER2 neg.), cT1c- cT4c, cN0/+ were randomized to arm A (Nab-Pac 125/Gem 1000 d1,8 q3w) vs. B (Nab-Pac 125/Carbo AUC2 d1,8 q3w). Randomization was stratified by center and nodal status. The trial is powered for pCR comparison by therapy arm and by presence vs. absence of early response markers. Pre-planned interim analysis aimed to identify a dynamic biomarker, e.g. drop of 3-week Ki-67, and to validate trial assumptions.
Results: 336 patients were enrolled from 47 centers between 06/13-02/15 (n=182 ArmA: Nab-Pac/Gem and n=154 ArmB: Nab-Pac/Carbo). 90% and 95% completed therapy according to protocol respectively (n.s.). Median age was 50y. At baseline: A/B: 73% and 74%% had G3 tumors, median Ki-67 of 70% and 75%; 62.6% and 62.9%% had cT2-4c tumors, pN0 status prior to chemotherapy was confirmed in 50.5% and 50%, respectively.
pCR (ypT0/is/ypN0) was A: 28.7% and B: 45.9% (p&lt;0.001). Total pCR (ypT0/ypN0) was A: 25.8% and B: 45.2% respectively (p &lt;0.001).
Nab/Gem arm was associated with significantly higher frequency of dose reductions (20.6% vs. 11.9% (p=0.03), treatment related SAE's (13% vs. 5%, p=0.02), grade 3-4 infections (6.1% vs. 1.3%, p=0.04) and ALAT elevations (11.7 vs. 3.3%, p=0.01) compared to the Nab-Carbo arm.
Within the planned interim analysis (n=130: A/B: 69/61), baseline Ki-67 (Nab- Pac/Carbo arm), age&gt;50 years, and low cellularity (&lt;500 tumor cells and/or Ki-67≤10% in the 3-week biopsy) (Nab-Pac/Gem arm) were positively associated with pCR by logistic regression analysis (separately by therapy arm). In all patients, therapy arm itself was significant for pCR.
Validation of responder definitions for the whole study will be presented at the meeting.
Conclusions:
This is the first large randomized study comparing two short 12-week anthracycline- free regimens in unselected TNBC. Our results suggest superior efficacy and excellent toxicity of Nab-Pac/Carbo vs. Gem. Longer A/T-Carbo containing regimens render quite comparable pCR rates, thus overtreatment by 4xEC in unselected TNBC may be present in some patients. Early response criteria seem to differ according to regimen; their assessment may be impaired by substantial tumor necrosis already after the first therapy cycle.
Citation Format: Gluz O, Nitz U, Liedtke C, Christgen M, Sotlar K, Grischke EM, Forstbauer H, Braun M, Warm M, Hackmann J, Uleer C, Aktas B, Schumacher C, Bangemann N, Lindner C, Kuemmel S, Clemens M, Potenberg J, Staib P, Kohls A, Pelz E, Kates RE, Wuerstlein R, Kreipe HH, Harbeck N. Comparison of 12 weeks neoadjuvant Nab-paclitaxel combined with carboplatinum vs. gemcitabine in triple- negative breast cancer: WSG-ADAPT TN randomized phase II trial. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-13-01.