LB49
Neo-tAnGo: a neoadjuvant randomised phase III trial of epirubicin / cyclophosphamide (EC) and paclitaxel (T) gemcitabine (G) in the treatment of women with high-risk early breast cancer (EBC)
H Earl1, A Vallier3, L Hiller4, N Fenwick5, M Iddawela6, L Hughes-Davies7, E Provenzano7, K McAdam8, S Houston10, T Hickish9, A Skene9, S Chan12, S Dean13, D Ritchie14, R Laing10, M Harries15, C Gallagher16, J Dunn4, G Wishart11, C Caldas2
1University of Cambridge, UK; 2NIHR Cambridge Biomedical Research Centre, UK; 3Cambridge Clinical Trials Centre, UK; 4Warwick Medical School, UK; 5CRUK Clinical Trials Unit, Birmingham, UK; 6CRUK Cambridge Research Institute, UK; 7Addenbrookes Hospital, Cambridge, UK; 8Peterborough Hospital NHS Trust, UK; 9Royal Bournemouth Hospital, UK; 10Royal Surrey County Hospital, UK; 11Cambridge Breast Unit, UK; 12Nottingham City Hospital, UK; 13Poole Hospital, Dorset, UK; 14Crosshouse Hospital, Ayrshire, UK; 15Guy's Hospital, London, UK; 16St. Bartholomew's Hospital, London, UK
Background
Neo-tAnGo used a 2-by-2 factorial design, addressing: (i) G in a sequential
neoadjuvant chemotherapy (CT) regimen of EC and T; and (ii) the sequencing of
these treatment components (EC then T G versus T G then EC).
Method
Patients (Pts) with early breast cancer were randomised to EC then T, T
then EC, EC then TG or TG then EC. All components were given x 4 cycles. (E=
90mg/m2 day (d)1 every (q) 21d; C=600mg/m2 d1 q21d;
T=175mg/m2 d1 q14d; G=2g/m2 d1 q14d.) The primary
endpoint was pathCR and 800 pts were required to detect 10% differences in
pathCR, 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 ooestrogen receptor (ER) status.
Results
Between Jan05 and Sep07, 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
<50mm, 50% node positive and 34% ER negative. The pathCR 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 TG then EC, showed pathCR of 20% (95% CI 16-24)
compared with 15% (95% CI 11-18) for EC then TG pts (p=0.03). pathCR for
HER2neg/HER2pos were 26%/18% for TG first sequence, compared with 17%/12% for
EC-first sequence. pathCR for ERneg/ERpos were 33%/14% for TG first sequence,
compared with 30%/7% for EC-first sequence.
Conclusion
Neo-tAnGo confirms the tAnGo trial and therefore provides evidence for
pathCR as a robust trial endpoint, and reliable predictor of longer term
outcomes. TG-first has demonstrated a significant improvement compared with
the more conventional anthracycline-first sequencing. This result may prove an
advantage for neoadjuvant trials combining first-line chemotherapy with
biological agents.
