Advantages with prophylactic PEG-rhG-CSF versus rhG-CSF in breast cancer patients receiving multiple cycles of myelosuppressive chemotherapy: an open-label, randomized, multicenter phase III study

• Published in: Breast cancer research and treatment 2018-04, Vol.168 (2), p.389-399
• Main Authors: Xie, Jie, Cao, Jun, Wang, Jing-fen, Zhang, Bai-hong, Zeng, Xiao-hua, Zheng, Hong, Zhang, Yang, Cai, Li, Wu, Yu-dong, Yao, Qiang, Zhao, Xiao-chun, Mao, Wei-dong, Jiang, Ai-Mei, Chen, Shao-shui, Yang, Shun-e, Wang, Shu-sen, Wang, Jian-hong, Pan, Yue-yin, Ren, Bi-yong, Chen, Yan-ju, Ouyang, Li-zhi, Lei, Kai-jian, Gao, Jing-hua, Huang, Wen-he, Huang, Zhan, Shou, Tao, He, Yan-ling, Cheng, Jing, Sun, Yang, Li, Wei-ming, Cui, Shu-de, Wang, Xin, Rao, Zhi-guo, Ma, Hu, Liu, Wei, Wu, Xue-yong, Shen, Wei-xi, Cao, Fei-lin, Xiao, Ze-min, Wu, Biao, Tian, Shu-yan, Meng, Dong, Shen, Peng, Wang, Bi-yun, Wang, Zhonghua, Zhang, Jian, Wang, Leiping, Hu, Xi-chun
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Breast Neoplasms, Male - drug therapy; Breast Neoplasms, Male - mortality; Breast Neoplasms, Male - pathology; Cancer patients; Cancer research; Care and treatment; Chemotherapy; Chemotherapy-Induced Febrile Neutropenia - epidemiology; Chemotherapy-Induced Febrile Neutropenia - etiology; Chemotherapy-Induced Febrile Neutropenia - prevention & control; China - epidemiology; Clinical Trial; Drug Administration Schedule; Female; Granulocyte Colony-Stimulating Factor - administration & dosage; Granulocyte Colony-Stimulating Factor - therapeutic use; Humans; Incidence; Kaplan-Meier Estimate; Labels; Male; Mastectomy; Medicine; Medicine & Public Health; Metastases; Middle Aged; Neutropenia; Oncology; Polyethylene glycol; Polyethylene Glycols - administration & dosage; Polyethylene Glycols - therapeutic use; Progression-Free Survival; Prospective Studies; Recombinant Proteins - administration & dosage; Recombinant Proteins - therapeutic use; Safety; Young Adult
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-017-4609-6

Background PEG-rhG-CSF reduces neutropenia and improves chemotherapy safety. In China’s registration trial (CFDA: 2006L01305), we assessed its efficacy and safety against rhG-CSF, and prospectively explored its value over multiple cycles of chemotherapy. Methods In this open-label, randomized, multicenter phase 3 study, breast cancer patients ( n  = 569) were randomized to receive PEG-rhG-CSF 100 µg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 µg/kg/d after chemotherapy. The primary endpoints were the incidence and duration of grade 3/4 neutropenia during cycle 1. Secondary endpoints included the incidence and duration of grade 3/4 neutropenia during cycles 2–4, the incidence of febrile neutropenia, and the safety. Results A once-per-cycle PEG-rhG-CSF at either 100 µg/kg or 6 mg was not different from daily injections of rhG-CSF for either incidence or duration of grade 3/4 neutropenia. Interestingly, a substantial difference was noted during cycle 2, and the difference became bigger over cycles 3–4, reaching a statistical significance at cycle 4 in either incidence ( P  = 0.0309) or duration ( P  = 0.0289) favoring PEG-rhG-CSF. A significant trend toward a lower incidence of all-grade adverse events was noted at 129 (68.98%), 142 (75.53%), and 160 (82.47%) in the PEG-rhG-CSF 100 µg/kg and 6 mg and rhG-CSF groups, respectively ( P  = 0.0085). The corresponding incidence of grade 3/4 drug-related adverse events was 2/187 (1.07%), 1/188 (0.53%), and 8/194 (4.12%), respectively ( P  = 0.0477). Additionally, PFS in metastatic patients preferred PEG-rhG-CSF to rhG-CSF despite no significance observed by Kaplan–Meier analysis ( n  = 49, P  = 0.153). Conclusions PEG-rhG-CSF is a more convenient and safe formulation and a more effective prophylactic measure in breast cancer patients receiving multiple cycles of chemotherapy.