title: Feasibility Study of EndoTAG-1, a Tumor Endothelial Targeting Agent, in Combination with Paclitaxel followed by FEC as Induction Therapy in HER2-Negative Breast Cancer.
abstract: BACKGROUND
  EndoTAG-1, a tumor endothelial targeting agent has shown activity in metastatic triple-negative breast cancer (BC) in combination with paclitaxel.
  
  
  METHODS
  HER2-negative BC patients candidates for neoadjuvant chemotherapy were scheduled to receive 12 cycles of weekly EndoTAG-1 22mg/m2 plus paclitaxel 70mg/m2 followed by 3 cycles of FEC (Fluorouracil 500mg/m2, Epirubicin 100mg/m2, Cyclophosphamide 500mg/m2) every 3 weeks followed by surgery. Primary endpoint was percent (%) reduction in Magnetic Resonance Imaging (MRI) estimated Gadolinium (Gd) enhancing tumor volume at the end of EndoTAG-1 plus paclitaxel administration as compared to baseline. Safety, pathological complete response (pCR) defined as no residual tumor in breast and axillary nodes at surgery and correlation between % reduction in MRI estimated tumor volume and pCR were also evaluated.
  
  
  RESULTS
  Fifteen out of 20 scheduled patients were included: Six patients with estrogen receptor (ER)-negative/HER2-negative and 9 with ER-positive/HER2-negative BC. Nine patients completed treatment as per protocol. Despite premedication and slow infusion rates, grade 3 hypersensitivity reactions to EndoTAG-1 were observed during the 1st, 2nd, 3rd and 6th weekly infusion in 4 patients, respectively, and required permanent discontinuation of the EndoTAG-1. Moreover, two additional patients stopped EndoTAG-1 plus paclitaxel after 8 and 9 weeks due to clinical disease progression. Two patients had grade 3 increases in transaminases and 1 patient grade 4 neutropenia. pCR was achieved in 5 of the 6 ER-/HER2- and in none of the 9 ER+/HER2- BC patients. The mean % reduction in MRI estimated tumor volume at the end of EndoTAG-1 plus paclitaxel treatment was 81% (95% CI, 66% to 96%, p<0.001) for the 15 patients that underwent surgery; 96% for patients with pCR and 73% for patients with no pCR (p = 0.04).
  
  
  CONCLUSIONS
  The EndoTAG-1 and paclitaxel combination showed promising preliminary activity as preoperative treatment, especially in ER-/HER2- patients. Further studies are warranted with need of premedication optimization.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01537536.
authors.affiliation: Medical Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.|Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Michail
authors.initials: M
authors.lastname: Ignatiadis
authors.affiliation: Breast International Group (BIG aisbl), Brussels, Belgium.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Zardavas
authors.affiliation: Department of Radiology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Lemort
authors.affiliation: Medigene AG, Planegg, Germany.
authors.forename: Celine
authors.initials: C
authors.lastname: Wilke
authors.affiliation: Medical Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Marie-Catherine
authors.initials: MC
authors.lastname: Vanderbeeken
authors.affiliation: Medical Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Veronique
authors.initials: V
authors.lastname: D'Hondt
authors.affiliation: Medical Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Evandro
authors.initials: E
authors.lastname: De Azambuja
authors.affiliation: Medical Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gombos
authors.affiliation: Medical Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Lebrun
authors.affiliation: Medical Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Lissandra
authors.initials: L
authors.lastname: Dal Lago
authors.affiliation: Medical Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Fanny
authors.initials: F
authors.lastname: Bustin
authors.affiliation: Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Marion
authors.initials: M
authors.lastname: Maetens
authors.affiliation: Department of Biostatistics, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Lieveke
authors.initials: L
authors.lastname: Ameye
authors.affiliation: Department of Surgery, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Veys
authors.affiliation: Service de Biostatistique et d'Epidémiologie, Gustave Roussy, Univ. Paris-Sud, Villejuif, France.
authors.forename: Stefan
authors.initials: S
authors.lastname: Michiels
authors.affiliation: Department of Radiology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Marianne
authors.initials: M
authors.lastname: Paesmans
authors.affiliation: Department of Pathology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Denis
authors.initials: D
authors.lastname: Larsimont
authors.affiliation: Medical Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.|Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Christos
authors.initials: C
authors.lastname: Sotiriou
authors.affiliation: Department of Surgery, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Nogaret
authors.affiliation: Medical Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.|Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.|Breast International Group (BIG aisbl), Brussels, Belgium.
authors.forename: Martine
authors.initials: M
authors.lastname: Piccart
authors.affiliation: Medical Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Awada
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use; D015251:Epirubicin / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D060828:Induction Chemotherapy; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D003520:Cyclophosphamide; D015251:Epirubicin; D005472:Fluorouracil; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases