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.

Abstract

PURPOSE:

Pegylated granulocyte-colony-stimulating factor (G-CSF) is frequently used to prevent febrile neutropenia (FN) in patients undergoing chemotherapy with a high risk of myelosuppression. This phase II/III study was conducted to determine the adequate dose of pegteograstim, a new formulation of pegylated G-CSF, and to evaluate the efficacy and safety of pegteograstim compared to pegfilgrastim.

METHODS:

In the phase II part, 60 breast cancer patients who were undergoing DA (docetaxel and doxorubicin) or TAC (docetaxel, doxorubicin, and cyclophosphamide) chemotherapy were randomly selected to receive a single subcutaneous injection of 3.6 or 6.0 mg pegteograstim on day 2 of each chemotherapy cycle. The phase III part was seamlessly started to compare the dose of pegteograstim at selected in phase II with 6.0 mg pegfilgrastim in 117 breast cancer patients. The primary endpoint of both the phase II and III parts was the duration of grade 4 neutropenia in the chemotherapy cycle 1.

RESULTS:

The mean duration of grade 4 neutropenia for the 3.6 mg pegteograstim (n = 33) was similar to that for the 6.0 mg pegteograstim (n = 26) (1.97 ± 1.79 days vs. 1.54 ± 0.95 days, p = 0.33). The 6.0 mg pegteograstim was selected to be compared with the 6.0 mg pegfilgrastim in the phase III part. In the phase III part, the primary analysis revealed that the efficacy of pegteograstim (n = 56) was non-inferior to that of pegfilgrastim (n = 59) [duration of grade 4 neutropenia, 1.64 ± 1.18 days vs. 1.80 ± 1.05 days; difference, -0.15 ± 1.11 (p = 0.36, 97.5 % confidence intervals = 0.57 and 0.26)]. The time to the absolute neutrophil count (ANC) recovery of pegteograstim (≥2000/μL) was significantly shorter than that of pegfilgrastim (8.85 ± 1.45 days vs. 9.83 ± 1.20 days, p < 0.0001). Other secondary endpoints showed no significant difference between the two groups. The safety profiles of the two groups did not differ significantly.

CONCLUSIONS:

Pegteograstim was shown to be as effective as pegfilgrastim in the reduction of chemotherapy-induced neutropenia in the breast cancer patients who were undergoing chemotherapy with a high risk of myelosuppression.

• Authors: Ki Hyeong Lee, Ji-Yeon Kim, Moon Hee Lee, Hye Sook Han, Joo Han Lim, Keon Uk Park, In Hae Park, Eun Kyung Cho, So Young Yoon, Jee Hyun Kim, In Sil Choi, Jae Hoo Park, Young Jin Choi, Hee-Jun Kim, Kyung Hae Jung, Si-Young Kim, Do-Youn Oh, Seock-Ah Im
• Journal: Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer (Support Care Cancer) Vol. 24 Issue 4 Pg. 1709-17 (Apr 2016) ISSN: 1433-7339 [Electronic] Germany
• PMID: 26423618 (Publication Type: Clinical Trial, Phase II, Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Recombinant Proteins
• Granulocyte Colony-Stimulating Factor
• pegfilgrastim
• Polyethylene Glycols
• pegylated granulocyte colony-stimulating factor
• Filgrastim

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Breast Neoplasms (drug therapy)
• Female
• Filgrastim
• Granulocyte Colony-Stimulating Factor (administration & dosage, therapeutic use)
• Humans
• Induction Chemotherapy (methods)
• Maximum Tolerated Dose
• Middle Aged
• Neutropenia (chemically induced)
• Polyethylene Glycols (administration & dosage, therapeutic use)
• Recombinant Proteins (administration & dosage, therapeutic use)