Park, K.H., Lee, S., Park, J.H., Kang, S.Y., Kim, H.Y., Park, I.H., . . . Seo, J.H. (2017). A randomized, multi-center, open-label, phase III study of once-per-cycle DA-3031, a pegylated G-CSF, in comparison with daily filgrastim in patients receiving TAC chemotherapy for breast cancer. Supportive Care in Cancer, 25, 505–511. 

To demonstrate that DA-3031 is not inferior to daily filgrastim to manage neutropenia

Patients were randomly assigned to receive daily filgrastim or DA-3031. Daily filgrastim at 100mcg/m² began 24 hours after chemotherapy was started and continued until absolute neutrophil count was at least 5 x 10⁹, or for 10 days. Those in the experimental group received 6 mg DA-3031 by subcutaneous injection on day 2 of each chemotherapy cycle. Patients received TAC chemotherapy every three weeks up to six cycles. The noninferiority margin set was two days for the duration of grade 4 neutropenia.

• N = 74 for ITT analysis, 63 completed the protocol
• MEAN AGE = 6.44
• AGE RANGE = 30–67 years
• FEMALES: 100%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: All had breast cancer and were receiving TAC chemotherapy.
• OTHER KEY SAMPLE CHARACTERISTICS: Previous colony-stimulating factor exposure, prior hematopoietic cell transplantation, and prior treatment with antibiotics within 72 hours of starting chemotherapy were exclusions.

• SITE: Multi-site   
• SETTING TYPE: Outpatient    
• LOCATION: Korea

PHASE OF CARE: Active antitumor treatment

Open-label, noninferiority, randomized, controlled trial

• Common Terminology Criteria for Adverse Events, version 4
• Time to absolute neutrophil count recovery to at least 2 x 10⁹/L

Mean duration of grade 4 neutropenia was 2.08 (SD = 0.85) days for the filgrastim group and 2.28 (SD = 1.14) days for the DA-3031 group. The difference between groups was 0.2 (SD = 1) days, supporting noninferiority of DA-3031. There were no significant differences between groups in absolute neutrophil coutn recovery time, incidence of febrile neutropenia, hospitalization, or requirement for intravenous antibiotics. There was no significant difference between groups in musculoskeletal symptoms associated with colony-stimulating factor administration. The findings were similar across all chemotherapy cycles. ITT and per protocol analysis were similar.

DA-3031, a once-per-cycle colony-stimulating factor, was not inferior to daily filgrastim.

• Small sample (< 100)
• Risk of bias (no blinding)
• ITT analysis had a 90% power.

DA-3031, a pegylated colony-stimulating factor was comparable to daily pegfilgrastim for neutropenia-related outcomes among women receiving TAC therapy. A once-per-cycle colony-stimulating factor can be more practical for patients because it does not require daily injections. Comparative costs of these two approaches was not discussed and may need to be considered in the selection of an approach.