253O - Neoadjuvant treatment with docetaxel plus lapatinib (L), trastuzumab (T), or both followed by an anthracycline based chemotherapy in HER2-positive...

Date 29 September 2014
Event ESMO 2014
Session Breast cancer, early stage
Topics Anticancer Agents
Breast Cancer
Biological Therapy
Presenter Herve Bonnefoi
Citation Annals of Oncology (2014) 25 (suppl_4): iv85-iv109. 10.1093/annonc/mdu327
Authors H. Bonnefoi1, W. Jacot2, M. Saghatchian3, C. Moldovan4, L. Venat-Bouvet5, K. Zaman6, E. Matos7, T. Petit8, M. Debled9, A. Bodmer10, P. Vuylsteke11, G. Jerusalem12, E. Brain13, O. Tredan14, C.G.M. Messina15, L. Slaets16, D. Cameron17
  • 1Anti Cancer Center, Institute Bergonié, 33076 - Bordeaux/FR
  • 2Service D'oncologie Médicale, Institut régional du Cancer de Montpellier (ICM) - Val d'Aurelle, Montpellier/FR
  • 3Dept Of Medicine, Institute Gustave Roussy, Villejuif/FR
  • 4Department Of Oncology, Centre Henri Becquerel, 76038 - Rouen/FR
  • 5Oncology, CHU de limoges, limoges/FR
  • 6Centre Pluridisciplinaire D'oncologie, Centre Hospitalier Universitaire Vaudois - CHUV, 1011 - Lausanne/CH
  • 7Dept. Of Medical Oncology, Institute of Oncology Ljubljana, 1000 - Ljubljana/SI
  • 8Department Of Medical Oncology, Paul Strauss Cancer Center and University of Strasbourg, FR-67065 - Strasbourg CEDEX/FR
  • 9Medicine, Institute Bergonie, 33076 - Bordeaux/FR
  • 10Medical Oncology Service, Hôpitaux universitaires de Genève, CH-1211 - Geneva/CH
  • 11Medical Oncology, Hopital Sainte-Elizabeth Namur, Namur/BE
  • 12Hematology And Medical Oncology, University of Liege, CHU Sart Tilman, BE-4000 - Liege/BE
  • 13Département D'oncologie Médicale, Institut Curie, FR-92210 - St Cloud/FR
  • 14Medical Oncology, Lyon Bérard Centre, 69008 - Lyon/FR
  • 15Medical Department, European Organisation for Research and Treatment of Cancer (EORTC AISBL), 1200 - Brussels/BE
  • 16Statistics, EORTC, 1200 - Brussels/BE
  • 17Oncology, University of Edinburgh, Edinburgh/GB



Neoadjuvant trials conducted using a double HER2-blockade with L and T, combined with different paclitaxel-containing chemotherapy regimens, have shown high pathological complete response (pCR) rates, but at the cost of important toxicity. We hypothesized that this toxicity might be due to a specific interaction between paclitaxel and L. This trial assesses the toxicity and activity of the combination of docetaxel with L and T.


Patients with stage IIA to IIIC HER2-positive breast cancer received 6 cycles of chemotherapy every 3 weeks (3 cycles of docetaxel 100 mg/m2 followed by 3 cycles of fluorouracil 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2). They were randomised to receive during the first 3 cycles either L (1000 mg orally daily) in arm A, T (4 mg/kg loading dose followed by 2 mg/kg weekly) in arm B, or T and L at the same dose in arm C. The primary endpoint was pCR rate defined as ypT0/is. Secondary endpoints included safety and toxicity. pCR rate defined as ypT0/is ypN0 was assessed as an exploratory analysis. The study was powered at 92.5% to reject the null hypothesis H0: 40% pCR, under HA: 60% pCR, at 1-sided α = 10%. In June 2012, arm A was closed for futility based on the results from other studies.


From October 2010 to January 2013, 128 patients were included in 14 centres. 6 patients were ineligible. pCR rates are reported below.

N pCR (%) ypT0/is definition
ypT0/is ypT0/isypN0 80% 2-sided CI p-value for H0 vs HA
A. L only 22 10 (45.5)  8 (38.1) 0.31-0.61 0.376
B. T only 52 27 (51.9) 27 (51.9) 0.42-0.62 0.054
C. L + T 48 29 (60.4) 27 (56.3) 0.50-0.70 0.003

Frequency (%) of most frequent grade 3-4 toxicities were in arms A/B/C: febrile neutropenia 23/15/10; diarrhea 9/2/18; infection other 9/4/8; and liver enzyme alteration 0/4/10. A dose reduction for any of the neoadjuvant drugs was required in 36/13/48 % of patients.


This study demonstrates, (1) a numerically higher pCR rate with double anti-HER2 blockade (L + T) plus chemotherapy, but suggests that the use of docetaxel rather than paclitaxel may not reduce toxicity; (2) a high pCR rate with T only with less toxicity.


All authors have declared no conflicts of interest.