Cardiac Safety of the Trastuzumab Biosimilar ABP 980 in Women with HER2-Positive Early Breast Cancer in the Randomized, Double-Blind, Active-Controlled LILAC Study
Abstract:Introduction Although the human epidermal growth factor receptor 2 (HER2) blocker trastuzumab is generally well tolerated, cardiotoxicity can be an important therapeutic limitation. Objective In this prespecified analysis, we compared the cardiac safety of the trastuzumab biosimilar ABP 980 (KAN-JINTI™) and the trastuzumab reference product (RP; Herceptin ®) in the phase III LILAC study (ClinicalTrials.gov identifier NCT01901146). Methods In the neoadjuvant phase of LILAC, after run-in chemotherapy, 725 patien… Show more
“…67 Similarly, in another active-controlled, double blind, randomized LILAC study, the cardiac safety of a biosimilar of trastuzumab ABP 980 was put in comparison with Herceptin, a reference product of trastuzumab and the chances of cardiac adverse events were comparatively low. 68 No pharmacokinetic dissimilarity was observed among the immunogenicity and safety characteristics were observed in FDA approved trustuzumab, European Union trastuzumab and biosimilar PF-05280014 and showed consistency with foregoing reports about trastuzumab. 69 In another study, PF-05280014 was compared with the reference trastuzumab-European union in terms of immunogenicity, efficacy and safety which demonstrated non-inferior pharmacokinetics in HER2 þ breast cancer patients receiving the neoadjuvant chemotherapy.…”
Stupendous elevation in the healthcare costs has followed with the inception of the current unconventional options of treatment available for cancer patients. There is a dire need of innovative financing approaches to lessen the financial load on healthcare system. Biosimilars are biological drugs consisting of an active ingredient from a reference biological drug that has a great potential of relieving financial load. Strict requirements from regulatory point of view are required as biosimilars are exceedingly similar to but not identical to the reference product. This provides with a certainty that no consequential differences from clinical point of view as compared to the respective biologics exists with regards to efficacy, safety and purity. Safety and effectiveness of biosimilars have been disclosed since more than 10 years of affirmations. However, there is a need to educate the healthcare professionals to abolish potential misconceptions and coalesce biosimilars into regular clinical practice. The present review focuses on providing an overview of regulatory aspects and requirements for biosimilars, the main challenges in the selection and development of biosimilars and the economic impact and financial savings observed in recent studies carried out in different parts of the world. In addition, we have discussed the different successful comparative studies which have been done in different parts of the world to depict the biosimilarity for monoclonal antibodies such as bevacizumab, trastuzumab and rituximab.
“…67 Similarly, in another active-controlled, double blind, randomized LILAC study, the cardiac safety of a biosimilar of trastuzumab ABP 980 was put in comparison with Herceptin, a reference product of trastuzumab and the chances of cardiac adverse events were comparatively low. 68 No pharmacokinetic dissimilarity was observed among the immunogenicity and safety characteristics were observed in FDA approved trustuzumab, European Union trastuzumab and biosimilar PF-05280014 and showed consistency with foregoing reports about trastuzumab. 69 In another study, PF-05280014 was compared with the reference trastuzumab-European union in terms of immunogenicity, efficacy and safety which demonstrated non-inferior pharmacokinetics in HER2 þ breast cancer patients receiving the neoadjuvant chemotherapy.…”
Stupendous elevation in the healthcare costs has followed with the inception of the current unconventional options of treatment available for cancer patients. There is a dire need of innovative financing approaches to lessen the financial load on healthcare system. Biosimilars are biological drugs consisting of an active ingredient from a reference biological drug that has a great potential of relieving financial load. Strict requirements from regulatory point of view are required as biosimilars are exceedingly similar to but not identical to the reference product. This provides with a certainty that no consequential differences from clinical point of view as compared to the respective biologics exists with regards to efficacy, safety and purity. Safety and effectiveness of biosimilars have been disclosed since more than 10 years of affirmations. However, there is a need to educate the healthcare professionals to abolish potential misconceptions and coalesce biosimilars into regular clinical practice. The present review focuses on providing an overview of regulatory aspects and requirements for biosimilars, the main challenges in the selection and development of biosimilars and the economic impact and financial savings observed in recent studies carried out in different parts of the world. In addition, we have discussed the different successful comparative studies which have been done in different parts of the world to depict the biosimilarity for monoclonal antibodies such as bevacizumab, trastuzumab and rituximab.
“…4 ). The overall frequency of cardiac disorders was low throughout the study [ 13 , 15 , 20 ]. The frequency of immunogenicity was found to be low and similar between groups, and no patient tested positive for neutralizing antibodies [ 15 ].…”
Section: Totality Of Evidence For Abp 980: a Brief Reviewmentioning
confidence: 99%
“…EOI event of interest, RP reference product Fig. 4 Left ventricular ejection fraction in the entire study [ 20 ]. LVEF left ventricular ejection fraction …”
Section: Totality Of Evidence For Abp 980: a Brief Reviewmentioning
confidence: 99%
“… Left ventricular ejection fraction in the entire study [ 20 ]. LVEF left ventricular ejection fraction …”
Section: Totality Of Evidence For Abp 980: a Brief Reviewmentioning
ABP 980 (KANJINTI TM , Amgen, Thousand Oaks, CA, USA; Amgen Europe B.V., The Netherlands) is a biosimilar to trastuzumab (Herceptin Ò), a monoclonal antibody that selectively binds human epidermal growth factor receptor-2 (HER2). Here we provide a brief overview of the totality of evidence (including analytical [structural and functional] characterization, nonclinical evaluation, and human pharmacokinetic [PK], pharmacodynamic, and clinical assessment comparing ABP 980 with trastuzumab reference product [RP]) that supported the approval of ABP 980, along with practical considerations on the reconstitution and use of the lyophilized product to ensure safe and effective administration. ABP 980 has been shown to be highly similar to the RP, with similar mechanism of action, binding, and potency. Key PK parameters, geometric means ratio (GMR [90% CI]) of C max and AUC inf, are comparable and within the equivalence margin of 0.80 to 1.25
“…77 Safety analyses showed that there were no clinically significant differences between the biosimilar and reference product. 76-78 Table 5 is a summary of other potential trastuzumab biosimilars currently being investigated. 79-81…”
Section: Trastuzumab Biosimilar In Breast Cancer and Gastric Cancermentioning
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.
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