Comparison of EP2006, a filgrastim biosimilar, to the reference: a phase III, randomized, double-blind clinical study in the prevention of severe neutropenia in patients with breast cancer receiving myelosuppressive chemotherapy.

Abstract

BACKGROUND:

Biosimilars of filgrastim are in widespread clinical use in Europe. This phase III study compares biosimilar filgrastim (EP2006), with the US-licensed reference product, Neupogen(®), in breast cancer patients receiving (neo)adjuvant myelosuppressive chemotherapy (TAC).

PATIENTS AND METHODS:

A total of 218 patients receiving 5 µg/kg/day filgrastim over six chemotherapy cycles were randomized 1:1:1:1 into four arms. Two arms received only one product (nonalternating), biosimilar or reference, and two arms (alternating) received alternating treatments during each cycle (biosimilar then reference or vice versa). The primary end point was duration of severe neutropenia (DSN) during cycle 1.

RESULTS:

The baseline characteristics were balanced between the four treatment arms. Noninferiority of biosimilar versus the reference was demonstrated: DSN (days) in cycle 1 was 1.17 ± 1.11 (biosimilar, N = 101) and 1.20 ± 1.02 (reference, N = 103), 97.5% confidence interval lower boundary for the difference was -0.26 days (above the predefined limit of -1 day). No clinically meaningful differences were observed regarding any other efficacy parameter: incidence of febrile neutropenia (FN); hospitalization due to FN; incidence of infections; depth and time of absolute neutrophil count (ANC) nadir and time to ANC recovery during cycle 1 and across all cycles. The pattern and frequency of adverse events were similar across all treatments.

CONCLUSION:

This study demonstrates that biosimilar and the reference filgrastim are similar with no clinically meaningful differences regarding efficacy and safety in prevention of severe neutropenia. Biosimilar filgrastim could represent an important alternative to the reference product, potentially benefiting public health by increasing access to filgrastim treatment.

STUDY NUMBER:

NCT01519700.

• Authors: K Blackwell, V Semiglazov, D Krasnozhon, I Davidenko, L Nelyubina, R Nakov, G Stiegler, P Singh, A Schwebig, S Kramer, N Harbeck
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 26 Issue 9 Pg. 1948-1953 (Sep 2015) ISSN: 1569-8041 [Electronic] England
• PMID: 26122726 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Chemical References

• Biosimilar Pharmaceuticals
• Granulocyte Colony-Stimulating Factor
• Filgrastim

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biosimilar Pharmaceuticals (therapeutic use)
• Breast Neoplasms (drug therapy)
• Double-Blind Method
• Female
• Filgrastim (analogs & derivatives, therapeutic use)
• Granulocyte Colony-Stimulating Factor (therapeutic use)
• Humans
• Middle Aged
• Neoadjuvant Therapy
• Neutropenia (drug therapy, prevention & control)
• Young Adult