The Global Need for a Trastuzumab Biosimilar for Patients With HER2-Positive Breast Cancer

Blackwell, Kimberly; Gligorov, J.; Jacobs, Ira; Twelves, Chris

doi:10.1016/j.clbc.2018.01.006

Cited by 64 publications

(45 citation statements)

References 83 publications

(175 reference statements)

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“…Unfortunately, the cost of medicine and the economic conditions of society has limited its access to a small number of patients. Data from the observational studies conducted between the years 2000 and 2015 clearly shows that patients with HER2+ MBC from United States (12%), Europe (27–54%) and China (27.1–49.2%), did not receive Trastuzumab or any other HER2-targeted agent as first and/or later line of treatment [ 1 ]. However, the introduction of trastuzumab biosimilars into the market would give access to an alternative yet cheaper therapy to a wider network of patients.…”

Section: Introductionmentioning

confidence: 99%

Randomized double-blind clinical trial comparing safety and efficacy of the biosimilar BCD-022 with reference trastuzumab

Alexeev

Khorinko²,

Mukhametshina

et al. 2020

BMC Cancer

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Background: BCD-022 is a trastuzumab biosimilar which was shown to be equivalent to reference trastuzumab in a wide panel of physicochemical studies as well as preclinical studies in vitro and in vivo. International multicenter phase III clinical trial was conducted to comparatively assess efficacy and safety of BCD-022 and reference trastuzumab in combination with paclitaxel used as the therapy of metastatic HER2(+) breast cancer. Pharmacokinetics and immunogenicity were also studied. Methods: Patients with no previous treatment for metastatic HER2(+) breast cancer were randomly assigned 1:1 to BCD-022 or reference trastuzumab and were treated with trastuzumab + paclitaxel. Therapy continued for 6 cycles of therapy (every 3 weeks), until progression of the disease or unbearable toxicity. Primary study endpoint was overall response rate. Study goal was to prove equivalent efficacy of BCD-022 and reference trastuzumab. Equivalence margins for 95% CI for difference in overall response rates were set at [− 20%; 20%]. Results: In total 225 patients were enrolled into the study, 115 in BCD-022 arm and 110 in reference trastuzumab arm. Overall response rate was 49.6% in BCD-022 arm and 43.6% in reference trastuzumab arm. Limits of 95% CI for difference of overall response rates between arms were [(− 8.05)-19.89%], thus, they lied within predetermined equivalence margins [− 20%; 20%]. Profile of adverse events was similar between groups (any AEs were reported in 93.81% of patients in BCD-022 arm and 94.55% of patients in reference arm). No unexpected adverse reactions were reported throughout the study. No statistically significant differences regarding antibody occurrence rate (either BAb or NAb) was found between BCD-022 (n = 3; 2.65%) and comparator (n = 4; 3.64%). Both drug products are characterized with low occurrence rate and short life of anti-trastuzumab antibodies. Pharmacokinetics assessment after 1st and 6th study drug injection also demonstrated equivalent PK parameters by all outcome measures: AUC 0-504 , С mах , Т max , T 1/2. Analysis of C trough did not reveal any significant inter-group differences as well.

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Section: Introductionmentioning

confidence: 99%

Randomized double-blind clinical trial comparing safety and efficacy of the biosimilar BCD-022 with reference trastuzumab

Alexeev

Khorinko²,

Mukhametshina

et al. 2020

BMC Cancer

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“…The clinical utilization of Tmab was firstly approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) in 1998 and in 2000, respectively, to treat patients with HER2+ metastatic breast cancer (MBC). Several years later (in 2006 and 2011), these two organisms also authorized the employment of this recombinant antibody as adjuvant therapy for patients with HER2+ early breast cancer (EBC) and, finally, in 2015 Tmab was added to the Essential Medicines List of the World Health Organization (WHO) [27]. Such addition was the outcome of the beneficial effects that Tmab has proven to have for women with HER2+ MBC and EBC when it is administered with chemotherapy, slowing down tumor progression, inducing tumor regression, and increasing patients' overall survival rate [28].…”

Section: Trastuzumab: More Than a Guide For Nanomedicinesmentioning

confidence: 99%

Trastuzumab: More than a Guide in HER2-Positive Cancer Nanomedicine

2020

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HER2 overexpression, which occurs in a fifth of diagnosed breast cancers as well as in other types of solid tumors, has been traditionally linked to greater aggressiveness. Nevertheless, the clinical introduction of trastuzumab has helped to improve HER2-positive patients’ outcomes. As a consequence, nanotechnology has taken advantage of the beneficial effects of the administration of this antibody and has employed it to develop HER2-targeting nanomedicines with promising therapeutic activity and limited toxicity. In this review, the molecular pathways that could be responsible for trastuzumab antitumor activity will be briefly summarized. In addition, since the conjugation strategies that are followed to develop targeting nanomedicines are essential to maintaining their efficacy and tolerability, the ones most employed to decorate drug-loaded nanoparticles and liposomes with trastuzumab will be discussed here. Thus, the advantages and disadvantages of performing this trastuzumab conjugation through adsorption or covalent bindings (through carbodiimide, maleimide, and click-chemistry) will be described, and several examples of targeting nanovehicles developed following these strategies will be commented on. Moreover, conjugation methods employed to synthesized trastuzumab-based antibody drug conjugates (ADCs), among which T-DM1 is well known, will be also examined. Finally, although trastuzumab-decorated nanoparticles and liposomes and trastuzumab-based ADCs have proven to have better selectivity and efficacy than loaded drugs, trastuzumab administration is sometimes related to side toxicities and the apparition of resistances. For this reason also, this review focuses at last on the important role that newer antibodies and peptides are acquiring these days in the development of HER2-targeting nanomedicines.

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“…Herceptin ® (trastuzumab) is the first humanized monoclonal antibody (mAb) and the first targeted IgG1 drug approved to treat human epidermal growth factor receptor 2 (HER2)positive breast cancer by inhibiting ligand-independent HER2 signaling pathways and inducing antibody-dependent cell-mediated cytotoxicity (ADCC) [1,2]. Trastuzumab was added into the World Health Organization (WHO) model list of essential medicines in 2015 [3]; however, 60% of patients with HER2-positive breast cancer may not have received this important therapy at some point during their course of treatment [4]. The application of biosimilars would improve affordability and bring increased access to trastuzumab to a broader patient population [5,6].…”

Section: Introductionmentioning

confidence: 99%

Demonstrating Analytical Similarity of Trastuzumab Biosimilar HLX02 to Herceptin® with a Panel of Sensitive and Orthogonal Methods Including a Novel FcγRIIIa Affinity Chromatography Technology

Xie

Zhang

et al. 2020

BioDrugs

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Background A biosimilar needs to demonstrate its similarity to the originator reference product (RP) in terms of structural and functional properties as well as nonclinical and clinical outcomes. Objectives The aim was to assess the analytical similarity between the trastuzumab biosimilar HLX02 and Europe-sourced Herceptin ® (EU-Herceptin ® ) and China-sourced Herceptin ® (CN-Herceptin ® ) following a quality-by-design (QbD) quality study and tier-based quality attribute evaluation. Methods A panel of highly sensitive and orthogonal methods, including a novel Fc gamma receptor IIIa (FcγRIIIa) affinity chromatography technique that enables quantitative comparison of glycan effects on effector function, was developed for the assessment. To ensure the full product variability was captured, ten batches of HLX02 were compared with 39 RP batches with expiry dates from August 2017 to March 2021. Results The extensive three-way similarity assessment demonstrated that HLX02 is highly similar to the RPs. Furthermore, the %afucose, %galactose, and FcγRIIIa affinity of the RPs were observed to first decrease and then return to the original level in relation to their expiry dates, and the RP batches can be subgrouped by their FcγRIIIa affinity chromatograms. HLX02 is demonstrated to be more similar to the RPs of the high FcγRIIIa affinity group. Conclusion Besides having an overall high analytical similarity to both EU-Herceptin ® and CN-Herceptin ® , HLX02 is more similar to Herceptin ® with high FcγRIIIa affinity, a result that demonstrates the power of the novel FcγRIIIa affinity chromatography technology in biosimilarity evaluation.

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The Global Need for a Trastuzumab Biosimilar for Patients With HER2-Positive Breast Cancer

Cited by 64 publications

References 83 publications

Randomized double-blind clinical trial comparing safety and efficacy of the biosimilar BCD-022 with reference trastuzumab

Randomized double-blind clinical trial comparing safety and efficacy of the biosimilar BCD-022 with reference trastuzumab

Trastuzumab: More than a Guide in HER2-Positive Cancer Nanomedicine

Demonstrating Analytical Similarity of Trastuzumab Biosimilar HLX02 to Herceptin® with a Panel of Sensitive and Orthogonal Methods Including a Novel FcγRIIIa Affinity Chromatography Technology

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