Paul Declerck1, Georgios Bakalos2, Elias Zintzaras3, Bettina Barton4, Thomas Schreitmüller5. 1. Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, University of Leuven, Leuven, Belgium. 2. Global Product Development Medical Affairs, Hoffmann-La Roche Ltd, Basel, Switzerland; Department of Biomathematics, University of Thessaly School of Medicine, Larisa, Greece. Electronic address: george.bakalos@roche.com. 3. Department of Biomathematics, University of Thessaly School of Medicine, Larisa, Greece; Center for Clinical Evidence Synthesis, The Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts. 4. Global Product Development Medical Affairs, Hoffmann-La Roche Ltd, Basel, Switzerland; SFL Regulatory Affairs & Scientific Communication, Basel, Switzerland. 5. Roche Pharma Technical Operations, Hoffmann-La Roche Ltd, Basel, Switzerland.
Abstract
PURPOSE: With the introduction of biosimilars of anticancer monoclonal antibodies (mAbs) in oncology, physicians are potentially confronted with the question whether it is clinically adequate to switch patients who are clinically stable on treatment with the reference product to a newly available biosimilar (or vice versa/from 1 biosimilar to another). For a proper impact assessment of switching, robust, product-specific, and clinically relevant evidence should be required, ideally including data from appropriately designed switching studies. In this article, we assess the current body of switching data available for approved or proposed biosimilars of anticancer mAbs. METHODS: PubMed was systematically searched and ClinicalTrials.gov and abstract databases of selected congresses were hand-searched to identify all switching studies including biosimilars of anticancer mAbs. FINDINGS: We identified 8 switching studies with biosimilars of rituximab (CT-P10, GP2013, PF-05280586, and BCD-020) and trastuzumab (ABP 980). Two were performed in oncology indications and the other 6 in rheumatoid arthritis (RA). Key elements of a well-designed switching study, such as randomization and blinding, were contained in several of the studies, but significant limitations were also present. The most frequent limitations were low statistical power because of small patient numbers, lack of an appropriate control arm, short follow-up, chosen outcome measures, and (for studies performed in RA) the concern whether switching data can be extrapolated to oncology indications. Accordingly, the data from these studies need to be interpreted with caution. Of note, all identified studies included a single switch only, whereas multiple switches may occur in the real-world setting. The scientific need to evaluate the impact of repeated switching has been recognized by the US Food and Drug Administration, who incorporated such a requirement in its draft guidance on interchangeability. IMPLICATIONS: From the scarce data available, the consequences of switching between reference product mAbs and their biosimilar(s) in the oncology setting are as yet unknown. Additional clinical evidence from well-designed switching studies is needed to guide switching decisions.
PURPOSE: With the introduction of biosimilars of anticancer monoclonal antibodies (mAbs) in oncology, physicians are potentially confronted with the question whether it is clinically adequate to switch patients who are clinically stable on treatment with the reference product to a newly available biosimilar (or vice versa/from 1 biosimilar to another). For a proper impact assessment of switching, robust, product-specific, and clinically relevant evidence should be required, ideally including data from appropriately designed switching studies. In this article, we assess the current body of switching data available for approved or proposed biosimilars of anticancer mAbs. METHODS: PubMed was systematically searched and ClinicalTrials.gov and abstract databases of selected congresses were hand-searched to identify all switching studies including biosimilars of anticancer mAbs. FINDINGS: We identified 8 switching studies with biosimilars of rituximab (CT-P10, GP2013, PF-05280586, and BCD-020) and trastuzumab (ABP 980). Two were performed in oncology indications and the other 6 in rheumatoid arthritis (RA). Key elements of a well-designed switching study, such as randomization and blinding, were contained in several of the studies, but significant limitations were also present. The most frequent limitations were low statistical power because of small patient numbers, lack of an appropriate control arm, short follow-up, chosen outcome measures, and (for studies performed in RA) the concern whether switching data can be extrapolated to oncology indications. Accordingly, the data from these studies need to be interpreted with caution. Of note, all identified studies included a single switch only, whereas multiple switches may occur in the real-world setting. The scientific need to evaluate the impact of repeated switching has been recognized by the US Food and Drug Administration, who incorporated such a requirement in its draft guidance on interchangeability. IMPLICATIONS: From the scarce data available, the consequences of switching between reference product mAbs and their biosimilar(s) in the oncology setting are as yet unknown. Additional clinical evidence from well-designed switching studies is needed to guide switching decisions.
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