title: Neoadjuvant breast cancer treatment as a sensitive setting for trastuzumab biosimilar development and extrapolation.
abstract: OBJECTIVE
  Identify sensitive end points and populations for similarity studies of trastuzumab and biosimilar monoclonal antibodies.
  
  
  METHODS
  We performed meta-analyses of trastuzumab clinical trials data: overall response rate (ORR) and progression-free survival in metastatic breast cancer (MBC), and total pathologic complete response (tpCR) and event-free survival in the neoadjuvant setting. Fitted models predicted the maximum loss in long-term efficacy for different similarity trial designs. Immunogenicity rates were investigated in different early breast cancer (EBC) study phases.
  
  
  RESULTS
  Using the same equivalence margins for ORR (MBC) and tpCR (EBC), the predicted maximum loss in long-term efficacy with a biosimilar candidate versus the reference product is smaller for tpCR than for ORR. In EBC this predicted loss could be controlled with feasible patient numbers for a typical clinical trial. Analyses suggested that a treatment-free follow-up phase is preferable for immunogenicity characterization.
  
  
  CONCLUSIONS
  Treatment of patients with neoadjuvant breast cancer represents a sensitive setting for establishing biosimilarity of efficacy and immunogenicity. tpCR is a sensitive end point in this setting to establish biosimilarity between a biosimilar candidate and its reference product.
authors.affiliation: Department of Obstetrics & Gynecology, Breast Cancer Center, Gynecologic Cancer Center, Sana Klinikum Offenbach, Starkenburgring 66, 63069 Offenbach, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Jackisch
authors.forename: Frank A
authors.initials: FA
authors.lastname: Scappaticci
authors.forename: Dominik
authors.initials: D
authors.lastname: Heinzmann
authors.forename: Fabio
authors.initials: F
authors.lastname: Bisordi
authors.forename: Thomas
authors.initials: T
authors.lastname: Schreitmüller
authors.forename: Gunter von
authors.initials: Gv
authors.lastname: Minckwitz
authors.forename: Javier
authors.initials: J
authors.lastname: Cortés
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000187:drug effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000453:epidemiology; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D020360:Neoadjuvant Therapy; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068878:Trastuzumab
keywords: HER2; Herceptin®; biosimilar; breast cancer; meta-analysis; metastatic breast cancer; neoadjuvant; trastuzumab