8MW0511，一种用于预防化疗引起的中性粒细胞减少症的新型长效粒细胞集落刺激因子融合蛋白：III期临床试验的最终结果
8MW0511, a novel, long-acting granulocyte-colony stimulating factor fusion protein for the prevention of chemotherapy-induced neutropenia: final results from the phase III clinical trial.
作者信息
Wang Biyun, Chen Xiuchun, Li Hongtao, Sun Jing, Jia Xinjian, Sun Tao, Yao Yumin, Wang Jingfen, Li Jincheng, Wang Xujuan, Wang Xiaojia, Geng Cuizhi, Ren Yu, Yang Liuzhong, Jia Jun, Chen Yiding, Li Zhihua, Huang Yunhui, Li Baojiang, Ren Guosheng, Chen Jian, Yu Shiyou, Mei Jiazhuan, Pei Zhidong, Liu Caixia, Cao Xuchen, Deng Chao, Huang Mingde, Pan Yueyin, Tu Yi, Zhang Zhiye, Luo Ruizhen, Wang Peipei, Dong Jingming, Zhao Honghuan, Lu Song, Zhu Chaolong, Cai Shaona, Wang Shuhai, Hu Xichun
机构信息
Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
出版信息
Breast Cancer Res. 2025 May 6;27(1):71. doi: 10.1186/s13058-025-02010-z.
BACKGROUND
8MW0511 is a novel, long-acting recombinant human granulocyte-colony stimulating factor (G-CSF) produced by the fusion of the N-terminus of highly active modified G-CSF with the C-terminus of human serum albumin (HSA). Current G-CSF treatments require frequent administration and have limitations in efficacy and convenience, highlighting the need for a longer-acting alternative with fewer injections and improved outcomes. Here, we report a phase III study comparing the efficacy and safety of 8MW0511 with those of the approved PEG-rhG-CSF.
METHODS
Patients with breast cancer were randomized at a 2:1 ratio to receive either 8MW0511 or PEG-rhG-CSF after four cycles of standard chemotherapy with docetaxel and cyclophosphamide, with or without doxorubicin. The primary efficacy endpoint was to evaluate the duration of severe neutropenia (DSN) between 8MW0511 and PEG-rhG-CSF during the first cycle.
RESULTS
Eligible patients were enrolled and randomly assigned to receive either 8MW0511 (n = 328) or PEG-rhG-CSF (n = 164). During the first cycle, the average DSN was 0.24 days for the 8MW0511 group and 0.25 days for the PEG-rhG-CSF group. The mean difference in DSN [-0.02 days (95% Confidence interval: -0.12, 0.08)] met the primary study endpoint. During cycles 2-4, the DSN results were consistent with those of cycle 1. The incidence of grade 4 neutropenia was lower in the 8MW0511 group than in the PEG-rhG-CSF group across all chemotherapy cycles. The incidence of febrile neutropenia (FN) across all cycles showed no significant difference between the two groups. Other efficacy endpoints and adverse events were comparable between the two groups.
CONCLUSIONS
The study findings confirm that 8MW0511 is not inferior to PEG-rhG-CSF in terms of efficacy and shows comparable safety profiles. Additionally, 8MW0511 has the potential to significantly decrease the duration of chemotherapy-induced neutropenia, along with a reduction in the occurrence of FN and severe neutropenia.
背景
8MW0511是一种新型长效重组人粒细胞集落刺激因子（G-CSF），由高活性修饰G-CSF的N端与人血清白蛋白（HSA）的C端融合而成。目前的G-CSF治疗需要频繁给药，在疗效和便利性方面存在局限性，这凸显了需要一种注射次数更少、疗效更好的长效替代药物。在此，我们报告一项III期研究，比较8MW0511与已获批的聚乙二醇化重组人粒细胞集落刺激因子（PEG-rhG-CSF）的疗效和安全性。
方法
乳腺癌患者在接受多西他赛和环磷酰胺，联合或不联合阿霉素的四个周期标准化疗后，按2:1的比例随机分组，分别接受8MW0511或PEG-rhG-CSF治疗。主要疗效终点是评估第一个周期中8MW0511组和PEG-rhG-CSF组之间严重中性粒细胞减少的持续时间。
结果
符合条件的患者入组并随机分配接受8MW0511（n = 328）或PEG-rhG-CSF（n = 164）治疗。在第一个周期中，8MW0511组的平均严重中性粒细胞减少持续时间为0.24天，PEG-rhG-CSF组为0.25天。严重中性粒细胞减少持续时间的平均差异[-0.02天（95%置信区间：-0.12，0.08）]达到了主要研究终点。在第2-4周期中，严重中性粒细胞减少持续时间的结果与第1周期一致。在所有化疗周期中，8MW0511组4级中性粒细胞减少的发生率低于PEG-rhG-CSF组。两组在所有周期中发热性中性粒细胞减少（FN）的发生率无显著差异。两组的其他疗效终点和不良事件具有可比性。
结论
研究结果证实，8MW0511在疗效方面不劣于PEG-rhG-CSF，且安全性相当。此外，8MW0511有可能显著缩短化疗引起的中性粒细胞减少的持续时间，同时减少发热性中性粒细胞减少和严重中性粒细胞减少的发生。
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