Final 10-year results of the Breast International Group 2-98 phase III trial and the role of Ki67 in predicting benefit of adjuvant docetaxel in patients with oestrogen receptor positive breast cancer
Por:
Sonnenblick, A, Francis, PA, Azim, HA, de Azambuja, E, Nordenskjold, B, Gutierez, J, Quinaux, E, Mastropasqua, MG, Ameye, L, Anderson, M, Lluch, A, Gnant, M, Goldhirsch, A, Di Leo, A, Barnadas, A, Cortes-Funes, H, Piccart, M, Crown, J
Publicada:
1 ago 2015
Resumen:
Aim: Breast International Group (BIG) 2-98 is a randomised phase III trial that tested the effect of adding docetaxel, either in sequence to or in combination with anthracycline-based adjuvant chemotherapy, in women with node-positive breast cancer (BC). Here, we present the 10-year final trial safety and efficacy analyses. We also report an exploratory analysis on the predictive value of Ki67 for docetaxel efficacy, in the BIG 2-98 and using a pooled analysis of three other randomised trials.
Patients and methods: 2887 patients were randomly assigned in a 2 x 2 trial design to one of four treatments. The primary objective was to evaluate the overall efficacy of docetaxel on disease free survival (DFS). Secondary objectives included comparisons of sequential docetaxel versus sequential control arm, safety and overall survival (OS). Ki67 expression was centrally evaluated by immunohistochemistry.
Results: After a median follow-up of 10.1 years, the addition of docetaxel did not significantly improve DFS or OS (hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.81-1.04; P = 0.16 and HR = 0.88, 95% CI = 0.76-1.03; P = 0.11, respectively). Sequential docetaxel did not improve DFS compared to the sequential control arm (HR = 0.86, 95% CI = 0.721.03; P = 0.10). In oestrogen receptor (ER)-positive tumours with Ki67 >= 14%, the addition of docetaxel resulted in 5.4% improvement in 10-year OS (P = 0.03, test for interaction = 0.1). In a multivariate model, there was a trend for improved DFS and OS in ER-positive patients with high Ki67 and treated with docetaxel (HR = 0.79, 95% CI = 0.63-1.01; P = 0.05 and HR = 0.76, 95% CI = 0.57-1.01; P = 0.06, respectively). A pooled analysis of four randomised trials showed a benefit of taxanes in highly proliferative ER-positive disease but not in low proliferating tumours (interaction test P = 0.01).
Conclusion: The DFS benefit previously demonstrated with sequential docetaxel is no longer observed at 10 years. However, an exploratory analysis suggested a benefit of docetaxel in patients with highly proliferative ER-positive BC. (C) 2015 Elsevier Ltd. All rights reserved.
Filiaciones:
Sonnenblick, A:
Univ Libre Bruxelles, Inst Jules Bordet, BrEAST Data Ctr, Dept Med, Brussels, Belgium
Francis, PA:
Peter MacCallum Canc Ctr, Melbourne, Vic, Australia
Australia & New Zealand Breast Canc Trials Grp, Newcastle, NSW, Australia
Int Breast Canc Study Grp, Bern, Switzerland
Azim, HA:
Univ Libre Bruxelles, Inst Jules Bordet, BrEAST Data Ctr, Dept Med, Brussels, Belgium
de Azambuja, E:
Univ Libre Bruxelles, Inst Jules Bordet, BrEAST Data Ctr, Dept Med, Brussels, Belgium
Nordenskjold, B:
Univ Sjukhuset, Swedish Breast Canc Grp, Linkoping, Sweden
Gutierez, J:
Clin Las Condes, Grp Oncol Cooperat Chileno Invest, Santiago, Chile
Quinaux, E:
Int Inst Drug Dev, Louvain La Neuve, Belgium
Mastropasqua, MG:
Univ Milan, Sch Med, Milan, Italy
Univ Milan, Dept Pathol, European Inst Oncol, Milan, Italy
Ameye, L:
Univ Libre Bruxelles, Inst Jules Bordet, Data Management Unit, Brussels, Belgium
Anderson, M:
Copenhagen Univ Hosp, Rigshosp, Dept Oncol, Copenhagen, Denmark
Danish Breast Canc Cooperat Grp, Copenhagen, Denmark
Lluch, A:
Univ Valencia, Hosp Clin Univ Valencia, INCLIVA, Dept Hematol & Med Oncol, E-46003 Valencia, Spain
Gnant, M:
Med Univ Vienna, Austrian Breast & Colorectal Canc Study Grp, Dept Surg, Vienna, Austria
Med Univ Vienna, Ctr Comprehens Canc, Austrian Breast & Colorectal Canc Study Grp, Vienna, Austria
Goldhirsch, A:
Int Breast Canc Study Grp, Bern, Switzerland
European Inst Oncol, Milan, Italy
Di Leo, A:
Hosp Prato, Ist Toscano Tumori, Sandro Pitigliani Med Oncol Dept, Prato, Italy
Barnadas, A:
Univ Autonoma Barcelona, Dept Med, Dept Med Oncol, Hosp Santa Creu & St Pau, E-08193 Barcelona, Spain
Cortes-Funes, H:
Univ Hosp 12 Octubre, Dept Med Oncol, Madrid, Spain
Piccart, M:
Univ Libre Bruxelles, Inst Jules Bordet, BrEAST Data Ctr, Dept Med, Brussels, Belgium
Crown, J:
St Vincets Univ Hosp, Dublin 4, Ireland
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