| Autor: |
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 |
| Předmět: |
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| Zdroj: |
JNCI: Journal of the National Cancer Institute; Jun2018, Vol. 110 Issue 6, p628-637, 10p |
| Abstrakt: |
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/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 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(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).Conclusions: 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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