Blackwell, K., Gascon, P., Krendyukov, A., Gattu, S., Li, Y., & Harbeck, N. (2018). 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. Annals of Oncology, 29, 244-249.

To confirm the safety and efficacy of the cost-effective filgrastim biosimilar EP2006 through a phase III, randomized, double blind study from the original PIONEER study, analyzing alternating treatments of EP2006 and reference filgrastim among patients receiving myelosuppressive chemotherapy. The alternating treatments were used to show there was no difference in efficacy, safety, or immunogenicity compared to patients who received EP2006 or filgrastim only.

Two patient groups from the original PIONEER study in which patients were randomized into one of four arms in a 1:1:1:1 ratio was analyzed in this study. Patients received an initial dose of either EP2006 or filgrastim and then alternated treatments over six cycles of chemotherapy TAC regimen (docetaxel 75 mg/m², doxorubicin 50 mg/m² and cyclophosphamide 500 mg/m²). The filgrastim was administered as 5 µg/kg body weight per day, subcutaneous injection from the second day of chemotherapy until reaching ANC ≥ 10 x 10⁹/l following nadir or for a maximum of 14 days.

• N = 109   
• AGE: Mean age = 48.6 years
• FEMALES: 100%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Women with confirmed breast cancer, Eastern Cooperative Oncology Group performance status ≤ 2, and adequate bone marrow function
• OTHER KEY SAMPLE CHARACTERISTICS: Patients were excluded if they had a history of myelogenous leukemia, myelodysplastic syndrome or concomitant sickle cell disease, concurrent or prior radiotherapy within four weeks of randomization, use of prophylactic antibiotics, prior chemotherapy or anticancer treatment of breast cancer or previous G-CSF therapy.

• SITE: Multi-site   
• SETTING TYPE: Not specified    
• LOCATION: 25 European centers

PHASE OF CARE: Active anti-tumor treatment

Randomized, double-blind, parallel-group, multicenter study of women (aged 18 years and older) with breast cancer receiving myelosuppressive chemotherapy

Multiple variables from the original dataset were measured including: FN (oral temperature 38.3 C and ANC < 0.5x10⁹/l on the same day), incidence of infections, incidence of hospitalizations due to FN, time and depth of ANC nadir (the patient’s lowest ANC in the respective chemotherapy cycle), time to ANC recovery, and ANC profile. Adverse events were also evaluated across all cycles of chemotherapy and included patients who received one or more dose of study medication and had one or more post-baseline safety assessment and the switched safety population of all patients who received one or more dose of study medication after cycle 1. Immunogenicity was evaluated.

Comparing the switched groups (n = 109) to the filgrastim reference group (n = 52), there were three patients (3.4%) in the switched group who had febrile neutropenia across cycles 2-6 compared to no patients with FN in the reference group. Infections occurred in 9.3% of patients in the switched group and 9.9% in the reference group. There were no differences between groups for depth of ANC nadir, time of ANC nadir, and time course of ANC recovery. Treatment emergent adverse events were similar between groups with 42.1% in the switched group and 39.2% in the reference group. No neutralizing antibodies against recombinant human G-CSF were detected.

The biosimilar EP2006 is as safe and effective as filgrastim. There was no compromise in immunogenicity in EP2006, and EP2006 was shown to be equally clinically meaningful to filgrastim, but is more cost-effective.

Knowledge regarding risks for infections in women with breast cancer receiving TAC therapy and the utilization of EP2006 as an alternative to filgrastim for cost-effective improved outcomes.