Neoadjuvant breast cancer treatment as a sensitive setting for trastuzumab biosimilar development and extrapolation

Future Oncol. 2015;11(1):61-71. doi: 10.2217/fon.14.187.


Aims: 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.

Conclusion: 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.

Keywords: HER2; Herceptin®; biosimilar; breast cancer; meta-analysis; metastatic breast cancer; neoadjuvant; trastuzumab.

Publication types

  • Meta-Analysis

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / drug effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / epidemiology
  • Clinical Trials as Topic
  • Disease-Free Survival
  • Female
  • Humans
  • Neoadjuvant Therapy*
  • Trastuzumab


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Trastuzumab