A Clinical Review of Biosimilars Approved in Oncology

Abstract

Objective: To summarize and review the clinical data of Food and Drug Administration (FDA)-approved biosimilars for use in treatment of cancer and the current challenges health care institutions face when implementing a newly approved biosimilar. Data Sources: A literature search of the following databases was performed between January 1, 2012, and December 31, 2019: PubMed, Google, and ClinicalTrials.gov. Search terms included the words biosimilar, bevacizumab, rituximab, and/or trastuzumab. Study Selection and Data Extraction: Only primary literature on biosimilars with an ongoing or completed phase 3 trial and/or FDA approval were included in the final analysis. Primary literature consisted of peer-reviewed publications, published abstracts, and any results posted on the ClinicalTrials.gov database. Data Synthesis: Clinical trials of FDA-approved biosimilars for bevacizumab, rituximab, and trastuzumab showed no significant differences with respect to efficacy, safety, and pharmacokinetics when compared with their reference products. Relevance to Patient Care and Clinical Practice: The anticipated growth of biologics in oncology and the recent introduction of biosimilars over the past few years have placed a lot of emphasis on biosimilars as a significant source of cost savings for the health care system. Our article compiles and analyzes existing data on biosimilar efficacy, safety, and financial impact. Conclusions: The major concerns of biosimilars revolve around their long-term efficacy and safety. Even with many questions to be answered, biosimilars have the potential for significant cost savings in the US health care system.

Real-World Use and Acceptance of Biosimilar Monoclonal Antibodies of Rituximab in Oncology Practice in the USA

“…As of November 2020, there are two FDA-approved rituximab biosimilars that were licensed in the USA under section 351(k) of the Public Health Service Act. Clinical trials demonstrated equivalent pharmacokinetics, as well as comparable safety and efficacy, for rituximab biosimilars in FL [12]. Two rituximab biosimilars (rituximab-abbs [Truxima R ] and rituximab-pvvr [Ruxience R ]) received FDA approval for all the approved oncology indications of the rituximab reference medication, including those utilizing monotherapy and combination therapies [13,14].…”

Safety and efficacy comparisons of rituximab biosimilars to the reference product in patients with cancer: a systematic meta‐analysis review

“…13 However, current literature consists mainly of Phase III clinical trials published by manufacturers of the biosimilar product where conflicts of interest may exist. 12 A 2019 systematic review and metaanalysis by Lee et al 14 involved both rheumatoid arthritis patients and NHL patients; however, more evidence has emerged since then which is specifically relevant to the oncology setting. [15][16][17][18][19][20][21]…”

“…Current evidence suggests no statistically significant difference in efficacy and safety between biosimilars and their reference biologics 13 . However, current literature consists mainly of Phase III clinical trials published by manufacturers of the biosimilar product where conflicts of interest may exist 12 . A 2019 systematic review and meta‐analysis by Lee et al 14 .…”

Biosimilar Impact on Oncology Clinical Trial Design and Operations

“…This consideration will be especially important for biologic medical products that are heavily used in SOC regimens, eg, bevacizumab, rituximab, and trastuzumab. 1 These scenarios will require additional time, money, and other resources from site research staff, eg, clinical research coordinators and investigational drug pharmacists, and should be factored into consideration when discussing budgeting and contracts between the site and the sponsor.…”

“…Because they are proteins with complex three-dimensional structures manufactured using eukaryotic cell machinery, even identical biological products can exhibit some variability. 1 In the United States, the FDA currently approaches biosimilar approval with a totality of evidence approach, whereas new biologic approval requires extensive clinical data. To maximize the cost benefits of biosimilar development and uptake, the FDA has shifted the focus of commercialization of a biosimilar on randomized clinical trials to emphasize comparative analytical, preclinical, and pharmacological data more heavily than clinical data.…”