• Christian Jackisch, Frank A Scappaticci, Dominik Heinzmann, Fabio Bisordi, Thomas Schreitmüller, Gunter von Minckwitz, and Javier Cortés.
• Department of Obstetrics & Gynecology, Breast Cancer Center, Gynecologic Cancer Center, Sana Klinikum Offenbach, Starkenburgring 66, 63069 Offenbach, Germany.
• Future Oncol. 2015 Jan 1; 11 (1): 61-71.

AimsIdentify sensitive end points and populations for similarity studies of trastuzumab and biosimilar monoclonal antibodies.MethodsWe 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.ResultsUsing 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.ConclusionTreatment 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.

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