Kubo, K., Miyazaki, Y., Murayama, T., Shimazaki, R., Usui, N., Urabe, A., . . . Tamura, K. (2016). A randomized, double-blind trial of pegfilgrastim versus filgrastim for the management of neutropenia during CHASE(R) chemotherapy for malignant lymphoma. British Journal of Haematology, 174, 563–570. 

To compare the safety and efficacy of pegfilgrastim and filgrastim in patients being treated with intensive chemotherapy for malignant lymphoma

Patient receiving CHASE(R) chemotherapy were randomized to receive either a single dose of pegfilgrastim or daily doses of filgrastim starting on day 4 after the completion of therapy. The primary endpoint was the duration of severe neutropenia.

• N = 111 randomized, 109 treated, 107 evaluable   
• MEDIAN AGE = 61 years (pegfilgrastim group), 60.5 years (filgrastim group)
• MALES: 66% (pegfilgrastim), 57.4% (filgrastim); FEMALES: 34% (pegfilgrastim), 42.6% (filgrastim)
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Pegfilgrastim: 94.3% (non-Hodgkin lymphoma [NHL]), 5.7% (Hodgkin lymphoma [HL]); filgrastim: 92.6% NHL, 7.4% HL
• OTHER KEY SAMPLE CHARACTERISTICS: Bone marrow involvement in 11.3% of the pegfilgrastim group and 9.3% of the filgrastim group; radiotherapy prior to current regimen in 13.2% of the pegfilgrastim group and 11.1% of the filgrastim group

• SITE: Multi-site   
• SETTING TYPE: Outpatient    
• LOCATION: Japanese Cancer Centers

• PHASE OF CARE: Active antitumor treatment

• Multicenter, randomized, double-blind, phase-III trial

The primary endpoint was the duration of severe neutropenia. Secondary endpoints were the duration of neutropenia and the incidence of febrile neutropenia.

The mean duration of severe neutropenia in patients receiving pegfilgrastim was 4.5 days (SD = 1.2) and 4.7 days (SD = 1.3) in the filgrastim group (p < 0.001). This demonstrated that noninferiority of pegfilgrastim compared to filgrastim. The neutrophil count peaked on the day after the start of the study drug administration for pegfilgrastim and on day 5 for filgrastim. The peak of the nadir was between days 8 and 10 for both groups and then returned to ≥ 1.0 x 10^9/L by day 16 in all patients. The mean duration of neutropenia was 5.2 (SD = 1.3) days for pegfilgrastim and 5.1 (SD = 1.3) days for filgrastim. The mean neutrophil count at nadir was 0.013 (SD = 0.026) x 10^9/L in the pegfilgrastim group and 0.017 (SD = 0.055) x 10^9/L in the filgrastim group. The incidence of febrile neutropenia was 56.6% in the pegfilgrastim group and 55.6% in the filgrastim group.

In respect to both primary and secondary endpoints, noninferiority was proven. While not an endpoint of the study, the adverse effects were very similar as well.

• Risk of bias (no control group)

Education about neutropenia, the duration of neutropenia, and the risk of febrile neutropenia as well as the importance of a granulocyte–colony-stimulating factor (G-CSF), whether filgrastim or pegfilgrastim, is important. In addition, nurses should provide education on the side effects of both medications.