Lee, K.H., Kim, J.Y., Lee, M.H., Han, H.S., Lim, J.H., Park, K.U., . . . Im, S.A. (2015). A randomized, multicenter, phase II/III study to determine the optimal dose and to evaluate the efficacy and safety of pegteograstim (GCPGC) on chemotherapy-induced neutropenia compared to pegfilgrastim in breast cancer patients: KCSG PC10-09. Supportive Care in Cancer, 24, 1709–1717. 

To identify an optimal dose of GCPGC and compare its safety and efficacy to that of pegfilgrastim

This study involved two phases—a phase II trial to identify optimal dosage followed by a phase III study to determine efficacy and safety of GCPGC in comparison to standard pegfilgrastim. In phase II, patients were randomized to receive either 3.6 mg  or 6 mg of GCPGC on day 2 of a cycle. There were no differences in neutropenic outcomes between groups, and researchers decided to use 6 mg for phase III. In phase III, patients were randomized to receive either 6 mg pegfilgrastim or 6 mg GCPGC on day 2 of their treatment cycle. Outcomes per treatment cycle were evaluated. During phase III, prophylactic antibiotics were not permitted in the first cycle but could be used in subsequent cycles according to physician discretion.

• N = 59 phase II, 117 phase III  
• MEDIAN AGE = 49 years phase II
• AGE RANGE = 28–74 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All had breast cancer and were scheduled to receive 4–6 cycles of docetaxel anddoxorubicin (DA) or docetaxel, doxorubicin, and cyclophosphamide (TAC) regimens

• SITE: Multi-site    
• SETTING TYPE: Not specified  
• LOCATION: South Korea

• PHASE OF CARE: Active antitumor treatment

• Noninferiority phase III, double-blind, multi-site randomized, controlled trial with active control

• Duration of grade 4 neutropenia during the first cycle (ANC < 500/mcl)
• Time to ANC recovery
• Incidence of febrile neutropenia (FN) defined as ANC < 500/mcl and with single oral temperature ≥ 38.3 C or two or more instances of temperature ≥ 38 C
• Hospital days
• IV antimicrobial usage

There were no significant differences in outcomes between groups other than time to ANC recovery. ANC recovery time after cycle 1 was a mean of 8.85 in the GCPGC group compared to 9.83 in the pegfilgrastim group (p < 0.0001). Incidence of treatment delay or dose reduction was higher in the pegfilgrastim group (p < 0.09). Adverse drug reactions that may have been associated with the study drug were 5.3% in the GCPGC group and 3.4% in the pegfilgrastim group, and included dizziness, eukocytosis, blurred vision, injection-site pain, pyrexia, headache, and peripheral sensory neuropathy.

GCPGC was not inferior to pegfilgrastim for prevention of febrile neutropenic complications in women receiving myelosuppressive chemotherapy. Additional research is needed to confirm its efficacy and safety.

• Risk of bias (sample characteristics)

GCPGC provided similar results as pegfilgrastim in terms of neutropeni- related complications with this type of myelosuppressive chemotherapy. However, adverse events appeared to be somewhat higher in the GCPGC group. Additional research is needed to confirm the safety profile of this new CSF.