Consequences of Switching to Anticancer Biosimilars Are "Unknown," Concludes Appraisal

Biosimilars of anticancer monoclonal antibodies are emerging in the therapeutic landscape, and while the body of evidence concerning switching to supportive care biosimilars—epoetin and filgrastim biosimilars—is robust, there are fewer data available concerning a switch to biosimilars of products such as rituximab, trastuzumab, and bevacizumab.

Writing in Clinical Therapeutics, Paul Declerck, PharmD, PhD, and colleagues present a critical appraisal of the available data on switching to anticancer biosimilars, gathering data from PubMed, abstract databases from relevant congresses, and the ClinicalTrials.gov registry.

The researchers identified 8 studies that assessed switches to trastuzumab or rituximab, only 2 of which were performed in oncology indications: the LILAC study of Amgen’s proposed trastuzumab biosimilar, ABP 980, in HER2-positive early breast cancer and a still-recruiting study of Celltrion’s CT-P10, a biosimilar rituximab, in CD20-positive low tumor burden follicular lymphoma. The remaining 6 studies assessed rituximab in patients with rheumatoid arthritis, and their findings may not be transferrable to oncology indications because of rituximab’s different method of action and dosing schedule in rheumatology versus oncology indications.

“The oncology study with the proposed trastuzumab biosimilar ABP 980… included many key elements of a good design for a switching study,” write the authors, adding that the study included a sensitive population, randomization preswitch, and a control arm. Outcome measures assessed included event-free survival, overall survival, immunogenicity, and safety. Switching did not increase the frequency or severity of adverse events (AEs), and there was no increase in the incidence of antidrug antibodies observed. The percentage of patients who had disease progression, recurrence, or death was similar between the switch and control arms.

By contrast, say the authors, the rituximab study “had some significant limitation in its design,” as it has no randomization before switching, a small switch group, and a “lacking” control arm. In both studies, write the authors, the number of patients should ideally be larger and the follow-up time greater in order to detect long-term differences in efficacy between the switch arms and control arms.

The authors suggest that the low number of available switching studies in oncology may be due to the inherently challenging nature of cancer treatment; disease indications differ in terms of progression, concomitant medications, and immunocompetence, and there exist ethical concerns about switching patients who are responding to their current therapy to a biosimilar that is not expected to improve their clinical outcomes.

However, as more biosimilars become available, patients are indeed likely to be switched, and “…if several biosimilars of the same reference product are available, patients may even be switched between 2 biosimilars that have not been directly compared with respect to switching…such switching scenarios are associated with an even higher level of residual uncertainty.”

The authors conclude that the consequences of switching to a biosimilar monoclonal antibody in oncology are as yet unknown, and call on medical societies and public bodies to provide useful leadership on the matter of switching and to develop evidence-based standards and guidelines.

Reference

Declerck P, Bakalos G, Zintzaras E, Barton B, Schreitmüller T. Monoclonal antibody biosimilars in oncology: critical appraisal of available data on switching. Clin Ther. 2018;40(5):798-809. doi: 10.1016/j.clinthera.2018.03.018.