Neo-tAnGo: A neoadjuvant randomized phase III trial of epirubicin/cyclophosphamide and paclitaxel ± gemcitabine in the treatment of women with high-risk early breast cancer (EBC): First report of the primary endpoint, pathological complete response (pCR).
Authors: Earl, H.M., Hickish, T. et al.
Journal: J Clin Oncol
Volume: 27
Issue: 15_suppl
Pages: 522
eISSN: 1527-7755
Abstract:522 Background: Neo-tAnGo used a 2-by-2 factorial design, addressing: (i) gemcitabine (G) in a sequential neoadjuvant chemotherapy (CT) regimen of epirubicin/cyclophosphamide (EC) and paclitaxel (T); and (ii) the sequencing of these treatment components (EC then T ± G versus T ± G then EC). METHODS: Patients (Pts) with early breast cancer (T2 tumours or above) were randomised to EC then T, T then EC, EC then TG or TG then EC. All components were given x 4 cycles. (E= 90 mg/m(2) day (d)1 every (q) 21d; C = 600 mg/m(2) d1 q21d; T = 175 mg/m(2) d1 q14d; G = 2,000 mg/m(2) d1 q14d.) The primary endpoint was pCR, defined as absence of invasive disease in the breast and axillary lymph nodes. 800 pts were required to detect 10% differences in the primary endpoint pCR rates, at the 5% (2-sided) significance level with 85% power. Stratification was by age, inflammatory/locally advanced disease, tumour size, clinical involvement of axillary nodes and oestrogen receptor (ER) status. RESULTS: Between January 2005 and September 2007, 831 pts were randomised by 88 consultants from 57 UK centres. Characteristics were balanced across groups: 63% <50 years old, 25% had inflammatory and/or locally advanced disease, 79% of tumours <50 mm, 50% node positive and 34% ER negative. Two-reader review of 813 (98%) eligible pts'. pathology reports, blinded to treatment arm, were carried out. pCR rates were 17% (95% CI 14-21) for EC&T pts and 17% (95% CI 14-21) for EC&TG pts (p = 0.98). However the sequence T±G then EC, showed pCR of 20% (95% CI 16-24) compared with 15% (95% CI 11-18) for EC then T±G pts (p = 0.03). Adjustment by stratification did not alter results. CONCLUSIONS: The Neo-tAnGo results confirm those of the adjuvant tAnGo trial in terms of gemcitabine effect (ASCO 2008). The sequence of T±G-first has demonstrated a significant advantage in pCR compared with the more conventional anthracycline-first sequencing. [Table: see text].
Source: PubMed