Safety and efficacy of alternating treatment with EP2006, a filgrastim biosimilar, and reference filgrastim: a phase III, randomised, double-blind clinical study in the prevention of severe neutropenia in patients with breast cancer receiving myelosuppressive chemotherapy

Blackwell, Kimberly; Gascón, Pere; Krendyukov, Andriy; Gattu, Sreekanth; Li, Y.; Harbeck, Nadia

doi:10.1093/annonc/mdx638

Cited by 22 publications

(16 citation statements)

References 19 publications

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“…21 A phase III trial of 218 patients with breast cancer receiving myelosuppressive chemotherapy with TAC (docetaxel/doxorubicin/cyclophosphamide) showed no clinically meaningful differences in efficacy, safety, or immunogenicity between filgrastim and filgrastimsndz, even in patients who alternated between the 2 in subsequent chemotherapy cycles. 18 A recently published combined analysis of this and another phase III trial on the safety of filgrastim-sndz in patients with breast cancer concluded that filgrastim-sndz has a safety profile consistent with previous studies of reference filgrastim. 22 Several retrospective studies also report similar efficacy between filgrastim-sndz and filgrastim for prophylaxis of chemotherapy-induced neutropenia.…”

Section: Biosimilarssupporting

confidence: 68%

“…Although no biosimilars have been designated as interchangeable by the FDA, limited data suggest that patients can alternate between the biosimilar and the originator biologic without any clinically meaningful differences in efficacy or safety. 18 Another concern is the potential for product drift that may arise during the manufacturing process of biologics and biosimilars, which could result in differences in efficacy and safety over time. Continued postmarketing surveillance of all biologic products is necessary for long-term monitoring of these agents.…”

Section: Biosimilarsmentioning

confidence: 99%

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NCCN Guidelines Insights: Hematopoietic Growth Factors, Version 1.2020

Becker

Griffiths²,

Alwan

et al. 2020

Journal of the National Comprehensive Cancer Network

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Management of febrile neutropenia (FN) is an integral part of supportive care for patients undergoing cancer treatment. The NCCN Guidelines for Hematopoietic Growth Factors provide suggestions for appropriate evaluation, risk determination, prophylaxis, and management of FN. These NCCN Guidelines are intended to guide clinicians in the appropriate use of growth factors for select patients undergoing treatment of nonmyeloid malignancies. These NCCN Guidelines Insights highlight important updates to the NCCN Guidelines regarding the incorporation of newly FDA-approved granulocyte-colony stimulating factor biosimilars for the prevention and treatment of FN.

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Section: Biosimilarssupporting

confidence: 68%

Section: Biosimilarsmentioning

confidence: 99%

NCCN Guidelines Insights: Hematopoietic Growth Factors, Version 1.2020

Becker

Griffiths²,

Alwan

et al. 2020

Journal of the National Comprehensive Cancer Network

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“…In some states, even if interchangeability is designated (after interchangeability regulatory requirements are finalized), providers or pharmacists must notify patient recipients of substitution . One U.S. study with 109 patients with cancer identified no safety concerns when biosimilar and reference filgrastim were administered after alternative chemotherapy cycles . Larger switching studies have not been reported.…”

Section: Interchangeabilitymentioning

confidence: 99%

Regulatory and Clinical Experiences with Biosimilar Filgrastim in the U.S., the European Union, Japan, and Canada

et al. 2019

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Biosimilar filgrastims are primarily indicated for chemotherapy-induced neutropenia prevention. They are less expensive formulations of branded filgrastim, and biosimilar filgrastim was the first biosimilar oncology drug administered in European Union (EU) countries, Japan, and the U.S. Fourteen biosimilar filgrastims have been marketed in EU countries, Japan, the U.S., and Canada since 2008, 2012, 2015, and 2016, respectively. We reviewed experiences and policies for biosimilar filgrastim markets in EU countries and Japan, where uptake has been rapid, and in the U.S. and Canada, where experience is rapidly emerging. U.S. regulations for designating biosimilar interchangeability are under development, and such regulations have not been developed in most other countries. Pharmaceutical substitution is allowed for new filgrastim starts in some EU countries and in Canada, but not Japan and the U.S. In EU countries, biosimilar adoption is facilitated with favorable hospital tender offers. U.S. adoption is reportedly 24%, while the second filgrastim biosimilar is priced 30% lower than branded filgrastim and 20% lower than the first biosimilar filgrastim approved by the U.S. Food and Drug Administration. Utilization is about 60% in EU countries, where biosimilar filgrastim is marketed at a 30%-40% discount. In Japan, biosimilar filgrastim utilization is 45%, primarily because of 35% discounts negotiated by Central Insurance and hospital-only markets. Overall, biosimilar filgrastim adoption barriers are small in many EU countries and Japan and are diminishing in Canada in the U.S. Policies facilitating improved U.S. adoption of biosimilar filgrastim, based on positive experiences in EU countries and Japan, including favorable insurance coverage; larger price discount relative to reference filgrastim pricing; closing of the "rebate trap" with transparent pricing information; formal educational efforts of patients, physicians, caregivers, and providers; and allowance of pharmaceutical substitution of biosimilar versus reference filgrastim, should be considered. The Oncologist 2019;24:537-548 Implications for Practice: We reviewed experiences and policies for biosimilar filgrastims in Europe, Japan, Canada, and the U.S. Postmarketing harmonization of regulatory policies for biosimilar filgrastims has not occurred. Acceptance of biosimilar filgrastims for branded filgrastim, increasing in the U.S. and in Canada, is commonplace in Japan and Europe. In the U.S., some factors, accepted in Europe or Japan, could improve uptake, including acceptance of biosimilars as safe andThe Oncologist 2019;24:537-548 www.TheOncologist.com New Drug Development and Clinical Pharmacology effective; larger cost savings, decreasing "rebate traps" where pharmaceutical benefit managers support branded filgrastim, decreased use of patent litigation/challenges, and allowing pharmacists to routinely substitute biosimilar for branded filgrastim.

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“…In this review, we discuss the clinical evidence for biosimilar filgrastim, including the phase III confirmatory studies assessing filgrastim as primary prophylaxis to reduce duration of chemotherapy-induced febrile neutropenia [12–14]. Following approval, clinical experience and real-world evidence have demonstrated the safety and efficacy of biosimilar filgrastim in patients with different tumor types undergoing myelosuppressive chemotherapy and in both autologous and allogeneic stem cell mobilization and severe chronic neutropenia.…”

Section: Introductionmentioning

confidence: 99%

Extrapolation in Practice: Lessons from 10 Years with Biosimilar Filgrastim

et al. 2019

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Biosimilar filgrastim (Sandoz) was approved in Europe in 2009 and, in 2015, was the first biosimilar approved in the USA. These authorizations were based on the "totality of evidence" concept, an approach that considers data from structural and functional characterization and comparability analysis and non-clinical and clinical studies. For biosimilar filgrastim, phase III confirmatory clinical studies were performed in the most sensitive population, patients with breast cancer undergoing myelosuppressive chemotherapy. In Europe and the USA, approval was granted for all indications of the reference biologic. Hence, stem cell mobilization and severe chronic neutropenia indications were approved on the basis of extrapolation, with no clinical data available at the time of market authorization in the EU. Although extrapolation is well-accepted in biologic development and regulatory contexts, it remains a misunderstood part of the biosimilarity concept in the medical community. Since approval, more than a decade of obtained clinical experience supports the totality of evidence and reassures clinicians regarding the efficacy and safety of biosimilar filgrastim. This includes real-world data from MONITOR-GCSF, a multicenter, prospective, observational study describing treatment patterns and clinical outcomes of patients with cancer (n = 1447) receiving biosimilar filgrastim for the prophylaxis of chemotherapy-induced neutropenia in solid tumors and hematological malignancies. Evidence is also available from unrelated healthy donors and those with severe chronic neutropenia. Together, the experience from a decade of use of biosimilar filgrastim includes over 24 million patient-days of exposure, which can help reassure oncologists that extrapolation is based on strong scientific evidence and works in practice.

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Safety and efficacy of alternating treatment with EP2006, a filgrastim biosimilar, and reference filgrastim: a phase III, randomised, double-blind clinical study in the prevention of severe neutropenia in patients with breast cancer receiving myelosuppressive chemotherapy

Abstract: There were no clinically meaningful results regarding efficacy, safety or immunogenicity when switching from reference to biosimilar filgrastim/EP2006, or vice versa.

Cited by 22 publications

References 19 publications

NCCN Guidelines Insights: Hematopoietic Growth Factors, Version 1.2020

NCCN Guidelines Insights: Hematopoietic Growth Factors, Version 1.2020

Regulatory and Clinical Experiences with Biosimilar Filgrastim in the U.S., the European Union, Japan, and Canada

Extrapolation in Practice: Lessons from 10 Years with Biosimilar Filgrastim

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