PMID- 29317553
OWN - NLM
STAT- MEDLINE
DCOM- 20191008
LR  - 20191008
IS  - 1549-490X (Electronic)
IS  - 1083-7159 (Print)
IS  - 1083-7159 (Linking)
VI  - 23
IP  - 4
DP  - 2018 Apr
TI  - Safety Profile of Biosimilar Filgrastim (Zarzio/Zarxio): A Combined Analysis of 
      Phase III Studies.
PG  - 403-409
LID - 10.1634/theoncologist.2017-0348 [doi]
AB  - BACKGROUND: Evaluation of adverse events (AEs) in pivotal registration trials and 
      ongoing postmarketing surveillance is important for all biologics, including 
      biosimilars. A combined analysis of two pivotal registration studies was 
      performed to strengthen evidence on safety for biosimilar filgrastim EP2006 in 
      patients with breast cancer receiving myelosuppressive chemotherapy, a sensitive 
      clinical setting to confirm biosimilarity of filgrastim. MATERIALS AND METHODS: 
      Data were combined from two phase III studies of biosimilar filgrastim EP2006. 
      The U.S. registration study was a randomized, double-blind comparison of 
      biosimilar and reference filgrastim in women aged >/=18 years with breast cancer, 
      receiving (neo)adjuvant treatment with TAC 
      (docetaxel + doxorubicin + cyclophosphamide). The European Union registration 
      study was a single-arm, open-label study of biosimilar filgrastim in women aged 
      >/=18 years with breast cancer receiving doxorubicin + docetaxel. Patients received 
      filgrastim as a subcutaneous injection on day 2 of each cycle for <14 days or 
      until the absolute neutrophil count reached 10 x 10(9)/L after the expected 
      nadir. Results were combined for cycles 1-4. RESULTS: A total of 277 patients 
      received biosimilar filgrastim EP2006. Patients had a mean (+/- standard deviation) 
      age of 51.1 (+/- 10.8) years, and 78.7% of patients had stage II or III breast 
      cancer. A total of 46 (20.6%) patients receiving biosimilar filgrastim had AEs 
      considered filgrastim-related. The most frequently reported filgrastim-related 
      AEs were musculoskeletal or connective tissue disorders (15.2%), including bone 
      pain (7.2%). One death (due to pulmonary embolism) occurred of a patient 
      receiving biosimilar filgrastim (not considered filgrastim-related). No patient 
      developed antidrug antibodies during the study. CONCLUSION: Biosimilar filgrastim 
      has a safety profile consistent with previous filgrastim studies and is effective 
      in preventing febrile neutropenia in patients with breast cancer. IMPLICATIONS 
      FOR PRACTICE: The biosimilar filgrastim EP2006 (Zarzio, Zarxio, biosimilar 
      filgrastim-sndz) has been approved in Europe since 2009 and in the U.S. since 
      2015. This combined analysis of two phase III studies provides additional 
      clinical evidence that the biosimilar filgrastim EP2006 has a safety profile 
      consistent with previous studies of reference filgrastim and supports large 
      postmarketing studies of EP2006 in Europe. Strengthening the evidence for 
      biosimilar filgrastim can help improve acceptance of biosimilars and increase 
      patient access to biologics.
CI  - (c) AlphaMed Press 2018.
FAU - Harbeck, Nadia
AU  - Harbeck N
AD  - Brustzentrum der Universitat Munchen (LMU), Munich, Germany 
      Nadia.Harbeck@med.uni-muenchen.de.
FAU - Gascon, Pere
AU  - Gascon P
AD  - Fundacio Clinic, Barcelona, Spain.
FAU - Krendyukov, Andriy
AU  - Krendyukov A
AD  - Hexal AG, Holzkirchen, Germany.
FAU - Hoebel, Nadja
AU  - Hoebel N
AD  - Hexal AG, Holzkirchen, Germany.
FAU - Gattu, Sreekanth
AU  - Gattu S
AD  - Hexal AG, Holzkirchen, Germany.
FAU - Blackwell, Kimberly
AU  - Blackwell K
AD  - Duke Cancer Institute, Durham, North Carolina, USA.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180109
PL  - England
TA  - Oncologist
JT  - The oncologist
JID - 9607837
RN  - 0 (Biosimilar Pharmaceuticals)
RN  - 0 (Hematologic Agents)
RN  - PVI5M0M1GW (Filgrastim)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use
MH  - Biosimilar Pharmaceuticals/adverse effects/*therapeutic use
MH  - Breast Neoplasms/*drug therapy/pathology
MH  - Clinical Trials, Phase III as Topic
MH  - Double-Blind Method
MH  - Female
MH  - Filgrastim/adverse effects/*therapeutic use
MH  - Hematologic Agents/adverse effects/*therapeutic use
MH  - Humans
MH  - Middle Aged
MH  - Neoadjuvant Therapy
MH  - Neoplasm Staging
MH  - Neutropenia/chemically induced/*prevention & control
MH  - Safety
MH  - Treatment Outcome
PMC - PMC5896710
OTO - NOTNLM
OT  - Biosimilar
OT  - EP2006
OT  - Filgrastim
OT  - Granulocyte colony-stimulating factor
COIS- Disclosures of potential conflicts of interest may be found at the end of this 
      article.
EDAT- 2018/01/11 06:00
MHDA- 2019/10/09 06:00
PMCR- 2019/04/01
CRDT- 2018/01/11 06:00
PHST- 2017/07/24 00:00 [received]
PHST- 2017/11/30 00:00 [accepted]
PHST- 2018/01/11 06:00 [pubmed]
PHST- 2019/10/09 06:00 [medline]
PHST- 2018/01/11 06:00 [entrez]
PHST- 2019/04/01 00:00 [pmc-release]
AID - theoncologist.2017-0348 [pii]
AID - ONCO12360 [pii]
AID - 10.1634/theoncologist.2017-0348 [doi]
PST - ppublish
SO  - Oncologist. 2018 Apr;23(4):403-409. doi: 10.1634/theoncologist.2017-0348. Epub 
      2018 Jan 9.