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
- Study type
- Clinical trial
- Study name
- EP2006
- Phase
- Phase 3
- Design
- Randomised, double-blind, phase 3 noninferiority trial with 1:1:1:1 randomisation into four groups
- Sample size
- 218 patients
- Source
- Annals of Oncology · 2015
- Trial registration
- NCT01519700
In plain words
During chemotherapy for breast cancer, the number of white blood cells that fight infection can drop sharply, and the drug filgrastim is used to prevent this problem. In this study, a biosimilar version of filgrastim (EP2006) was compared with the original drug (Neupogen). The results showed that both drugs kept the period of severely low white blood cells equally short and had similar side effects.
Key results
Treatment arms and regimens
TAC chemotherapy IV on day 1 every 3 weeks for 6 cycles: docetaxel 75 mg/m², doxorubicin 50 mg/m² and cyclophosphamide 500 mg/m². Filgrastim 5 µg/kg body weight per day subcutaneously from day 2 of each cycle until ANC recovered to 10 × 109/L after the nadir or for a maximum of 14 days; biosimilar filgrastim EP2006 in all 6 cycles (53 patients).
TAC chemotherapy IV on day 1 every 3 weeks for 6 cycles: docetaxel 75 mg/m², doxorubicin 50 mg/m² and cyclophosphamide 500 mg/m². Filgrastim 5 µg/kg body weight per day subcutaneously from day 2 of each cycle until ANC recovered to 10 × 109/L after the nadir or for a maximum of 14 days; reference filgrastim Neupogen in all 6 cycles (52 patients).
TAC chemotherapy IV on day 1 every 3 weeks for 6 cycles: docetaxel 75 mg/m², doxorubicin 50 mg/m² and cyclophosphamide 500 mg/m². Filgrastim 5 µg/kg body weight per day subcutaneously from day 2 of each cycle until ANC recovered to 10 × 109/L after the nadir or for a maximum of 14 days; biosimilar and reference alternating each cycle (starting with the biosimilar).
TAC chemotherapy IV on day 1 every 3 weeks for 6 cycles: docetaxel 75 mg/m², doxorubicin 50 mg/m² and cyclophosphamide 500 mg/m². Filgrastim 5 µg/kg body weight per day subcutaneously from day 2 of each cycle until ANC recovered to 10 × 109/L after the nadir or for a maximum of 14 days; reference and biosimilar alternating each cycle (starting with the reference). The two alternating groups together had 109 patients.
Source of the regimen details: Full text of the paper (PMC4551159, Patients and Study design sections)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Women aged 18 and over with histologically proven breast cancer scheduled for neoadjuvant or adjuvant TAC chemotherapy (docetaxel 75, doxorubicin 50 and cyclophosphamide 500 mg/m²); ECOG at most 2 and adequate bone marrow function. Exclusion criteria: history of myeloid leukaemia, myelodysplastic syndrome or sickle cell disease, concurrent radiotherapy or radiotherapy within 4 weeks before randomisation, prophylactic antibiotics, prior chemotherapy or anticancer treatment for breast cancer and prior G-CSF treatment. 25 centres in Russia, Ukraine, Hungary, Latvia, Slovakia and the Czech Republic (December 2011 to June 2013); randomisation stratified by adjuvant or neoadjuvant treatment.
Endpoints
Primary endpoint: duration of severe neutropenia (DSN) in the first chemotherapy cycle. Other efficacy measures: incidence of febrile neutropenia (FN), hospitalisation due to FN, incidence of infections, depth and time to nadir of the absolute neutrophil count (ANC) and time to ANC recovery in the first cycle and across all cycles.
Safety and side effects
The pattern and frequency of adverse events were similar in all groups; the most common were alopecia, nausea, asthenia, fatigue and bone pain. Grade 3 or 4 neutropenia in cycle 1: 77% (biosimilar) versus 79% (reference); febrile neutropenia 4.7% versus 1.9% (1 hospitalisation each). Adverse events possibly related to filgrastim in cycle 1: 20.6% versus 19.6%. One death from pulmonary embolism occurred in the biosimilar group (day 6 of cycle 1) and was not considered related to the drug; serious adverse events were numerically (not significantly) more frequent in the biosimilar group (5 versus 2 patients). Injection-site reactions were rare and mild to moderate.
Clinical significance and place in guidelines
Based on this study, the filgrastim biosimilar EP2006 does not differ in a clinically meaningful way from the reference product in efficacy and safety for the prevention of severe neutropenia and may be a suitable alternative that could increase access to treatment. The drug's approval status and its place in clinical guidelines should be checked separately, as they are not mentioned in the abstract of the paper.
Limitations
According to the abstract: the comparison was made only in patients with breast cancer receiving one chemotherapy regimen (TAC), and the primary endpoint was measured in the first chemotherapy cycle. Other limitations should be checked in the full text of the paper.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.