Neoadjuvant Breast Cancer Treatment as a Sensitive Setting for Trastuzumab Biosimilar Development and Extrapolation

ABSTRACT

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:

• biosimilar
• breast cancer
• HER2
• Herceptin^®
• meta-analysis
• trastuzumab
• neoadjuvant
• metastatic breast cancer

Financial & competing interests disclosure

C Jackisch and J Cortés are members of the Roche Speakers Bureau and are consultants for Roche Pharma. Gunter von Minckwitz received research grants from Roche and GSK, consultancy fees from Roche, Mylan and Amgen, and speaker honoraria from Roche and Amgen. Frank A Scappaticci, Dominik Heinzmann, Fabio Bisordi and Thomas Schreitmüller are employees of, and own shares in, F. Hoffmann-La Roche Ltd. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Support for third-party writing assistance for this manuscript was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland.