Bevacizumab biosimilar BEVZ92 versus reference bevacizumab in combination with FOLFOX or FOLFIRI as first-line treatment for metastatic colorectal cancer: a multicentre, open-label, randomised controlled trial

Romera, A.; Peredpaya, Sergiy; Shparyk, Yaroslav; Bondarenko, Igor; Bariani, Giovanni M.; Abdalla, Kathia Cristina; Roca, Enrique; Franke, Fábio; Cruz, Felipe Melo; Ramesh, Anita; Ostwal, Vikas; Shah, Priyanka A.; Rahuman, Sajeed Abdul; Paravisini, Alexandra; Huerga, Camino; García, Ángel Sánchez; Millán, Susana

doi:10.1016/s2468-1253(18)30269-3

Cited by 30 publications

(36 citation statements)

References 20 publications

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“…Biosimilars are defined as biologic medical products that are highly similar to an approved reference product, notwithstanding minor clinically insignificant differences [8,9]. The clinical needs for affordable bevacizumab treatment have resulted in the development of a number of biosimilar molecules [10][11][12][13][14][15][16][17][18][19][20][21]. As of August 2020, two bevacizumab biosimilars (Zirabev ® and Mvasi ® ) have been approved by the United States Food and Drug Administration (FDA) [22,23] and the European Medicines Agency (EMA) [24,25], and two (Byvasda ® and Ankada ® ) by the Chinese National Medical Products Administration (NMPA) [26,27].…”

Section: Introductionmentioning

confidence: 99%

A phase 1 randomized study compare the pharmacokinetics, safety and immunogenicity of HLX04 to reference bevacizumab sourced from the United States, the European Union, and China in healthy Chinese male volunteers

Zhu

Sun

et al. 2021

Cancer Chemother Pharmacol

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Purpose To compare the pharmacokinetic profiles, safety and immunogenicity of proposed bevacizumab biosimilar HLX04 with reference bevacizumab in healthy Chinese males. Methods In this double-blind Phase 1 study, healthy volunteers (N = 208) were randomized 1:1:1:1 to a single 3 mg/kg intravenous infusion of HLX04 or reference bevacizumab sourced from the United States (bevacizumab-US), the European Union (bevacizumab-EU) or China (bevacizumab-CN). Co-primary endpoints were area under the serum concentration–time profile (AUC) from time zero extrapolated to infinity (AUC0–inf) and from zero to last quantifiable concentration (AUClast). Secondary endpoint was the maximum serum drug concentration (Cmax). Study participants were monitored for treatment-emergent adverse events (TEAEs) and samples were collected for anti-drug antibody (ADA) testing throughout the study. Results Pharmacokinetic parameters were similar across groups. The respective geometric least-squares mean ratios (GLSMR) of AUC0–inf, AUClast and Cmax were: 95.7%, 96.0% and 101.8% for HLX04 versus bevacizumab-US; 94.3%, 94.6% and 100.5% for HLX04 versus bevacizumab-EU; and 90.0%, 90.4% and 98.2% for HLX04 versus bevacizumab-CN. For all test-to-reference comparisons, two-sided 90% confidence intervals of GLSMR for AUC0–inf, AUClast and Cmax fell in the pre-specified bioequivalence range (80–125%). There were no notable differences in the frequency, nature and/or grade of TEAEs. No deaths were reported and no ADAs were detected during the study. Conclusion HLX04 had similar safety and pharmacokinetic profiles to reference bevacizumab in healthy Chinese males, supporting the confirmatory Phase 3 study investigating the efficacy and safety equivalence between HLX04 and bevacizumab in patients with metastatic colorectal cancer (NCT03511963). Clinical trial registration The study was registered with Clinicaltrials.gov, NCT03483649.

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Section: Introductionmentioning

confidence: 99%

A phase 1 randomized study compare the pharmacokinetics, safety and immunogenicity of HLX04 to reference bevacizumab sourced from the United States, the European Union, and China in healthy Chinese male volunteers

Zhu

Sun

et al. 2021

Cancer Chemother Pharmacol

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“…A study by Romera et al 69 verified the similarity between bevacizumab biosimilar (BEVZ92) with the reference bevacizumab in combination with the FOLFOX or FOLFIRI protocols for first-line treatment for metastatic colorectal cancer. The results presented demonstrated equivalence between the BEVZ92 and the pharmacokinetically reference bevacizumab, with no differences in the efficacy, immunogenicity, and safety profiles in the first-line treatment of colorectal cancer associated with the FOLFOX or FOLFIRI protocols.…”

Section: Biosimilar Drugs In Oncologymentioning

confidence: 95%

Can biosimilar products be interchangeable? Pharmaceutical perspective in the implementation of biosimilars in oncology

Soares

Cavalcanti

Vasconcelos

2021

J Oncol Pharm Pract

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Objective To evaluate the safety in the interchangeability of biosimilar products approved for cancer treatment from a pharmaceutical perspective. Methods A literature review was carried out using the descriptors “Biosimilar”, “Oncology Therapy”, “Interchangeable drugs” and “Biological Products”, in the Sciencedirect, MEDLINE, and CAPLUS databases. Results Fifty-one articles were selected, which addressed the importance of establishing standards that prove the efficacy and safety of biosimilars with reference products, as well as the growing interest of the pharmaceutical industry in the development of biosimilars and the impact on costs and changes in the perspective of the treatment of cancer patients. Conclusions As they are large and complex molecules, it is impossible to obtain identical copies of their reference products, which generates conflicts and concerns on the part of the pharmaceutical class regarding the safety in the interchangeability of these products, highlighting the importance of pharmacovigilance in this process.

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“…This was a randomized, open-label, comparative trial in which patients with previously untreated mCRC received treatment with BEVZ92 plus conventional chemotherapy with either FOLFOX (folinic acid, 5-fluorouracil, and oxaliplatin) or FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan) until disease progression, unacceptable toxicity, or withdrawal of consent (Table 3). 31 Confirmatory Comparative Clinical Studies. To confirm biosimilarity, comparative phase III studies are conducted to show that there are no clinically meaningful differences in efficacy and safety between the proposed biosimilar and the RP.…”

Section: Demonstrating Biosimilaritymentioning

confidence: 99%

“…In the comparative clinical pharmacology study of BEVZ92 and bevacizumab RP in mCRC, the preliminary efficacy and safety results showed no differences in clinical benefit, PFS, safety, or immunogenicity between the treatment arms. 31…”

Section: Demonstrating Biosimilaritymentioning

confidence: 99%

Clinical and Regulatory Considerations for the Use of Bevacizumab Biosimilars in Metastatic Colorectal Cancer

Taı̈eb

Aranda

Raouf

et al. 2021

Clinical Colorectal Cancer

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Biosimilars e biological medicines highly similar to a licensed reference product (RP) e can mitigate the risk of drug shortages by providing treatment alternatives and, with their lower costs, increase patient access to medication and reduce health care expenditure. However, limited knowledge of biosimilar approval processes and lack of confidence in their quality and efficacy can limit their uptake. Importantly, biosimilars are approved based on tightly controlled regulatory pathways to demonstrate that the physical, chemical, and biological properties of the proposed biosimilar are highly similar to the RP, with no clinically meaningful differences. Initially, a battery of highly sensitive in vitro studies are performed, comparing critical quality attributes between the proposed biosimilar and RP. Subsequently, in vivo pharmacodynamic studies compare the activity and physiologic effects of the biosimilar and RP. Finally, clinical studies are conducted, including a pharmacokinetic equivalence study and a confirmatory comparative clinical trial. The latter is performed in the most sensitive patient population for which the RP is licensed, to provide the greatest possibility of identifying any clinically meaningful differences between the proposed biosimilar and RP. When equivalent safety and efficacy have been demonstrated in one setting, the totality of evidence, together with scientific justification that there are no anticipated differences between the RP and proposed biosimilar in mechanism of action, pharmacokinetics, immunogenicity or toxicity, allows extrapolation into indications where clinical studies were not performed with the proposed biosimilar. Here, we review the approval process for biosimilars, focusing on the licensing of bevacizumab biosimilars and their extrapolation to metastatic colorectal cancer.

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Bevacizumab biosimilar BEVZ92 versus reference bevacizumab in combination with FOLFOX or FOLFIRI as first-line treatment for metastatic colorectal cancer: a multicentre, open-label, randomised controlled trial

Cited by 30 publications

References 20 publications

A phase 1 randomized study compare the pharmacokinetics, safety and immunogenicity of HLX04 to reference bevacizumab sourced from the United States, the European Union, and China in healthy Chinese male volunteers

A phase 1 randomized study compare the pharmacokinetics, safety and immunogenicity of HLX04 to reference bevacizumab sourced from the United States, the European Union, and China in healthy Chinese male volunteers

Can biosimilar products be interchangeable? Pharmaceutical perspective in the implementation of biosimilars in oncology

Clinical and Regulatory Considerations for the Use of Bevacizumab Biosimilars in Metastatic Colorectal Cancer

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