title: Neoadjuvant treatment with docetaxel plus lapatinib, trastuzumab, or both followed by an anthracycline-based chemotherapy in HER2-positive breast cancer: results of the randomised phase II EORTC 10054 study.
abstract: BACKGROUND
  Neoadjuvant trials conducted using a double HER2 blockade with lapatinib and trastuzumab, combined with different paclitaxel-containing chemotherapy regimens, have shown high pathological complete response (pCR) rates, but at the cost of important toxicity. We hypothesised that this toxicity might be due to a specific interaction between paclitaxel and lapatinib. This trial assesses the toxicity and activity of the combination of docetaxel with lapatinib and trastuzumab.
  
  
  METHODS
  Patients with stage IIA to IIIC HER2-positive breast cancer received six cycles of chemotherapy (three cycles of docetaxel followed by three cycles of fluorouracil, epirubicin, cyclophosphamide). They were randomised 1 : 1 : 1 to receive during the first three cycles either lapatinib (1000 mg orally daily), trastuzumab (4 mg/kg loading dose followed by 2 mg/kg weekly), or trastuzumab + lapatinib at the same dose. The primary end point was pCR rate defined as ypT0/is. Secondary end points included safety and toxicity. pCR rate defined as ypT0/is ypN0 was assessed as an exploratory analysis. In June 2012, arm A was closed for futility based on the results from other studies.
  
  
  RESULTS
  From October 2010 to January 2013, 128 patients were included in 14 centres. The percentage of the 122 assessable patients with pCR in the breast, and pCR in the breast and nodes, was numerically highest in the lapatinib + trastuzumab group (60% and 56%, respectively), intermediate in the trastuzumab group (52% and 52%), and lowest in the lapatinib group (46% and 36%). Frequency (%) of the most common grade 3-4 toxicities in the lapatinib /trastuzumab/lapatinib + trastuzumab arms were: febrile neutropenia 23/15/10, diarrhoea 9/2/18, infection (other) 9/4/8, and hepatic toxicity 0/2/8.
  
  
  CONCLUSIONS
  This study demonstrates a numerically modest pCR rate increase with double anti-HER2 blockade plus chemotherapy, but suggests that the use of docetaxel rather than paclitaxel may not reduce toxicity.
  
  
  BACKGROUND
  NCT00450892.
authors.affiliation: Department of Medical Oncology, Institut Bergonié Comprehensive Cancer Centre, Université de Bordeaux, INSERM U916, Bordeaux h.bonnefoi@bordeaux.unicancer.fr.
authors.forename: H
authors.initials: H
authors.lastname: Bonnefoi
authors.affiliation: Department of Medical Oncology, Centre Val D'Aurelle-Paul Lamarque, Montpellier.
authors.forename: W
authors.initials: W
authors.lastname: Jacot
authors.affiliation: Department of Medical Oncology, Gustave Roussy, Villejuif.
authors.forename: M
authors.initials: M
authors.lastname: Saghatchian
authors.affiliation: Department of Medical Oncology, Centre Henri Becquerel, Rouen.
authors.forename: C
authors.initials: C
authors.lastname: Moldovan
authors.affiliation: Department of Medical Oncology, Centre Hospitalier Universitaire, Limoges, France.
authors.forename: L
authors.initials: L
authors.lastname: Venat-Bouvet
authors.affiliation: Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
authors.forename: K
authors.initials: K
authors.lastname: Zaman
authors.affiliation: Department of Medical Oncology, Institute of Oncology, Ljubljana, Ljubljana University Clinic, Golnik, Slovenia.
authors.forename: E
authors.initials: E
authors.lastname: Matos
authors.affiliation: Department of Medical Oncology, Centre Paul Strauss, Strasbourg, France.
authors.forename: T
authors.initials: T
authors.lastname: Petit
authors.affiliation: Gyneco-Oncology Unit, Hôpitaux Universitaires de Genève (HUG), Geneva, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Bodmer
authors.affiliation: Department of Medical Oncology, Institut Bergonié Comprehensive Cancer Centre, Université de Bordeaux, INSERM U916, Bordeaux.
authors.forename: N
authors.initials: N
authors.lastname: Quenel-Tueux
authors.affiliation: Department of Medical Oncology, Institut Bergonié Comprehensive Cancer Centre, Université de Bordeaux, INSERM U916, Bordeaux.
authors.forename: C
authors.initials: C
authors.lastname: Chakiba
authors.affiliation: Department of Medical Oncology, Hôpital St Elisabeth, Namur.
authors.forename: P
authors.initials: P
authors.lastname: Vuylsteke
authors.affiliation: Department of Medical Oncology, Centre Hospitalier Universitaire (Sart Tilman), Liege, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Jerusalem
authors.affiliation: Medical Oncology and Clinical Research Unit, Ensemble Hospitalier de L'Institut Curie, Hôpital René Huguenin, St-Cloud.
authors.forename: E
authors.initials: E
authors.lastname: Brain
authors.affiliation: Department of Medical Oncology, Centre Léon Bérard, Lyon, France.
authors.forename: O
authors.initials: O
authors.lastname: Tredan
authors.affiliation: Department of Statistics, European Organisation for Research and Treatment of Cancer (EORTC), Brussels, Belgium.
authors.forename: C G M
authors.initials: CG
authors.lastname: Messina
authors.affiliation: Department of Statistics, European Organisation for Research and Treatment of Cancer (EORTC), Brussels, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Slaets
authors.affiliation: Edinburgh Breast Unit and Edinburgh University Cancer Research Centre, Western General Hospital, Edinburgh, UK.
authors.forename: D
authors.initials: D
authors.lastname: Cameron
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077341:Lapatinib; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D011799:Quinazolines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D043823:Taxoids / Q000008:administration & dosage; D000068878:Trastuzumab / Q000008:administration & dosage
chemical_list: D018943:Anthracyclines; D003520:Cyclophosphamide; D000077143:Docetaxel; D015251:Epirubicin; D005472:Fluorouracil; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab
keywords: HER2; breast cancer; lapatinib; neoadjuvant chemotherapy; pathological response; trastuzumab