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Efficacy of 12 weeks neoadjuvant nab-paclitaxel combined with carboplatinum vs. gemcitabine in triple-negative breast cancer: WSG-ADAPT TN randomized phase II trial.
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
Abstracts by Oleg Gluz:
Efficacy of 12-weeks of neoadjuvant TDM1 with or without endocrine therapy in HER2-positive hormone-receptor-positive early breast cancer: WSG-ADAPT HER2+/HR+ phase II trial.Meeting: 2015 ASCO Annual Meeting | Abstract No: 506Category: Breast Cancer—HER2/ER - HER2+
Hormone receptor discordance between local and central pathology with RT-PCR analysis: Results from multicenter Phase III WSG-PlanB trial.Meeting: 2015 ASCO Annual Meeting | Abstract No: e11555Category: Breast Cancer—HER2/ER - ER+