The US Food and Drug Administration (FDA) recently approved the trastuzumab biosimilar Ogivri™ (trastuzumab-dkst) for treatment of breast cancer based on physicochemical and functional biosimilarity and phase 3 efficacy and safety data in metastatic breast cancer (MBC). Clinical trials evaluating trastuzumab biosimilars for treatment of ERBB2-positive breast cancer have assessed bioequivalence through comparative efficacy outcomes as neoadjuvant therapy for early-stage breast cancer (EBC) or first-line therapy for MBC. We conducted a systematic review to examine whether demonstrating bioequivalence in terms of efficacy is different in EBC vs MBC.
MEDLINE and conference abstracts were identified using the search terms “biosimilar” AND “trastuzumab” from 1 January 2013 to 14 March 2018. Abstracts and manuscripts were manually reviewed to assess availability of efficacy data comparing the proposed biosimilar with reference trastuzumab.
A total of 84 results were obtained. After selection for studies with comparative clinical efficacy results, 8 phase 3 clinical trials for 6 proposed biosimilars were included in the final analysis: 4 in EBC (primary efficacy outcome, pathologic complete response [pCR]) and 4 in MBC (primary efficacy outcome, overall response rate [ORR]). In all trials, the proposed biosimilar was equivalent to reference trastuzumab in terms of efficacy. Two biosimilars (CT-P6 [2 different formulations], Celltrion, Incheon, Republic of Korea; PF-05280014, Pfizer, New York, NY) showed equivalent efficacy in both the EBC and MBC settings.
All biosimilars assessed demonstrated equivalent efficacy to reference trastuzumab, regardless of clinical setting. Two biosimilars demonstrated equivalent efficacy in both the EBC and MBC settings. Although the FDA and European Medicines Agency determine biosimilarity based on totality of evidence, both the EBC and MBC settings appear to have similar sensitivity and be appropriate for determination of equivalent efficacy based on regulatory guidelines and clinical results. Together, these data support extrapolation between settings.
Clinical trial identification
Legal entity responsible for the study
Editorial assistance was provided under the direction of the authors by Tyler Rork, PhD, and Jennifer Rossi, MA, ELS, MedThink SciCom, with support from Mylan Inc.
H.S. Rugo: Travel, accommodations, expenses: Puma Biotechnology, Mylan, Lilly, Pfizer, Merck, Amgen, Teva research funding (all to the UC Regents): Merck, Pfizer, Lilly, Novartis, Macrogenics, Eisai, Genentech/Roche, OBI Pharma. G. Curigliano: Speaker fees: Pfizer, Novartis, Roche and Lilly. F. Cardoso: Consultant or advisor: Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi-Sankyo, Eisai, GE Oncology, Genentech, GlaxoSmithKline, Macrogenics, Merck-Sharp, Merus BV, Mylan, Mundipharma, Novartis, Pfizer, Pierre-Fabre, Roche, Sanofi, Seattle Genetics, and Teva. J. Cortes Castan: Honoraria: Roche, Novartis, Eisai, Celgene, Pfizer; Consultant or advisor: Roche, Celgene, AstraZeneca, Cellestia Biotech, Biothera, and Merus. E. Pennella, R. Muniz: Employee of Mylan Inc. and may hold stock with the company. All other authors have declared no conflicts of interest.