147088-156

Efficacy of 12 weeks neoadjuvant nab-paclitaxel combined with carboplatinum vs. gemcitabine in triple-negative breast cancer: WSG-ADAPT TN randomized phase II trial.

Subcategory: 
Category: 
Breast Cancer—Triple-Negative/Cytotoxics/Local Therapy
Session Type and Session Title: 
Poster Session, Breast Cancer—Triple-Negative/Cytotoxics/Local Therapy
Abstract Number: 

1032

Poster Board Number: 
Board #146
Citation: 
J Clin Oncol 33, 2015 (suppl; abstr 1032)
Author(s): 
Oleg Gluz, Ulrike Nitz, Matthias Christgen, Eva-Maria Grischke, Helmut Forstbauer, Michael Wilhelm Braun, Mathias Warm, Christoph Uleer, Bahriye Aktas, Claudia Schumacher, John Hackmann, Nikola Bangemann, Peter Staib, Christoph Lindner, Sherko Kummel, Cornelia Liedtke, Ronald E. Kates, Rachel Wuerstlein, Hans Heinrich Kreipe, Nadia Harbeck, West German Study Group ADAPT TN Investigators; West German Study Group, Moenchengladbach, Germany; Geriatric Breast Center, Evangelina Bethesda Hospital for Breast Diseases, Nordrhein-Westfalen, Germany; Hannover Medical School, Hannover, Germany; Universitӓts-Frauenklinik Tübingen, Tübingen, Germany; Praxisnetzwerk Hämatologie / intern. Onkologie, Troisdorf, Germany; Rotkreuzklinikum, Munich, Germany; Kliniken der Stadt Köln - Krankenhaus Holweide, Cologne, Germany; Gyn.-onkologische Gemeinschaftspraxis Hildesheim, Hildesheim, Germany; University Hospital Essen, Essen, Germany; St. Elisabeth Hospital, Köln, Germany; Marien-Hospital Witten, Witten, Germany; Charité-Universitätsmedizin Berlin, Berlin, Germany; St. Antonius Hospital, Eschweiler, Germany; Agaplesion Diakonieklinikum Hamburg, Hamburg, Germany; Kliniken Essen-Mitte (KEM), Essen, Germany; University of Schleswig-Holstein Campus Luebeck, Luebeck, Germany; REK Consulting, Otterfing, Germany; University of Munich, Munich, Germany; University of Munich, Otterfing, Germany

Abstract Disclosures

Abstract: 

Background: Pathological complete response (pCR) is associated with improved prognosis in TNBC, but optimal chemotherapy remains unclear. Neoadjuvant weekly nab-paclitaxel (Nab-Pac) has higher efficacy than conventional paclitaxel, with maximum benefit in TNBC. Both gemcitabine (Gem) and carboplatinum (Carbo) are interesting partners for taxane combinations, as metastastic BC data reveal. 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 (ER/PR < 1%, centrally 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). The trial is powered for pCR comparison by therapy arm and by presence vs. absence of early response. Pre-planned interim analysis aimed to identify a dynamic biomarker, e.g. drop of 3-week Ki-67, and to validate trial assumptions. Results: The first 130 randomized patients were assessed for interim analysis: 69 in arm A, 61 in arm B; 84% vs. 93% completed study therapy (p = 0.1), respectively. Median age was 50y. At baseline, 93% had G3 tumors, median Ki-67 was 65%; 64% had cT2-4c tumors, 23% cN+. SAE analysis: 20 SAEs in 10 patients (A) vs. 5 SAEs in 5 patients (B) were reported (p = 0.3). pCR occurred in 36% of patients overall; A: 25%, B: 49.2% (p = .006). In contrast to a strong association of baseline Ki-67 with pCR, no significant association between pCR and dynamic Ki-67 change was detected among patients with at least 500 tumor cells in the 3-week biopsy; however, 49% of patients had less than 500 tumor cells, and this condition appeared to be positively associated with pCR. Conclusions: Early results suggest rather intriguing high efficacy and favorable toxicity of short-term therapy with Nab-Pac + Carbo vs. Gem in unselected TNBC. Identification of early-proliferation responders by pre-specified protocol for Ki-67 drop failed, possibly due to substantial tumor necrosis already after first therapy cycle. 336 pts were enrolled at 45 sites by 01/2015. The study will be completed in April, 2015. Clinical trial information: NCT01815242