Comparison of Neoadjuvant Nab-Paclitaxel+Carboplatin vs Nab-Paclitaxel+Gemcitabine in Triple-Negative Breast Cancer : Randomized WSG-ADAPT-TN Trial Results
| Autor: | Oleg Gluz, Ulrike Nitz, Cornelia Liedtke, Matthias Christgen, Eva-Maria Grischke, Helmut Forstbauer, Michael Braun, Mathias Warm, John Hackmann, Christoph Uleer, Bahriye Aktas, Claudia Schumacher, Nikola Bangemann, Christoph Lindner, Sherko Kuemmel, Michael Clemens, Jochem Potenberg, Peter Staib, Andreas Kohls, Raquel von Schumann, Ronald Kates, Johannes Schumacher, Rachel Wuerstlein, Hans Heinrich Kreipe, Nadia Harbeck |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Cancer Research medicine.medical_specialty Paclitaxel medicine.medical_treatment Medizin Triple Negative Breast Neoplasms Gastroenterology Deoxycytidine Disease-Free Survival Carboplatin 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Breast cancer Internal medicine Albumins Antineoplastic Combined Chemotherapy Protocols Medicine Humans Triple-negative breast cancer Aged Chemotherapy business.industry Middle Aged medicine.disease Chemotherapy regimen Gemcitabine Neoadjuvant Therapy Regimen 030104 developmental biology Treatment Outcome Oncology Tolerability chemistry 030220 oncology & carcinogenesis Lymphatic Metastasis Female business medicine.drug |
| Popis: | 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.Patients with TNBC (estrogen receptor/progesterone receptor1%, human epidermal growth factor receptor 2-negative, cT1c-cT4c, cN0/+) were randomly assigned to A: nab-paclitaxel 125 mg/m2/gemcitabine 1000 mg/m2 d1,8 three times weekly (q3w); vs B: nab-paclitaxel 125 mg/m2/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 decrease30% or 500 invasive tumor cells in the three-week serial biopsy). All statistical tests were two-sided.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(dBA) = 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).This first large randomized trial suggests high efficacy and excellent tolerability of a neoadjuvant nab-paclitaxel/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. |
| Databáze: | OpenAIRE |
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