Department of Oncotherapy, University of Szeged, Korányi Fasor 12, Szeged, 6720, Hungary.
Institutul Oncologic Prof. Dr. I. Chiricuta, Republicii Bulevardul 34-36, 400015, Cluj-Napoca, Romania.
BMC Cancer. 2019 Feb 6;19(1):122. doi: 10.1186/s12885-019-5329-6.
Treatment with recombinant human granulocyte-colony stimulating factor (G-CSF) is accepted standard for prevention of chemotherapy-induced neutropenia. RGB-02 (Gedeon Richter) is a proposed biosimilar to pegylated G-CSF (Neulasta®, Amgen) with sustained release properties. This is a randomized, comparative, double-blind, multicenter study to evaluate efficacy and safety of RGB-02 in breast cancer patients receiving cytotoxic regimen.
Two hundred thirty-nine women presenting with breast cancer were randomized to RGB-02 (n = 121) and the reference product (n = 118). All patients received up to 6 cycles of docetaxel/doxorubicin chemotherapy combination and a once-per-cycle injection of a fixed 6 mg dose of pegfilgrastim. Primary endpoint was the duration of severe neutropenia (ANC < 0.5 × 10/L) in Cycle 1 (2-sided CI 95%). Secondary endpoints included incidence and duration of severe neutropenia (in cycles 2-4), incidence of febrile neutropenia, time to ANC recovery, depth of ANC nadir, and safety outcomes.
The mean duration of severe neutropenia in Cycle 1 was 1.7 (RGB-02) and 1.6 days (reference), with a difference (LS Mean) of 0.1 days (95% CI -0.2, 0.4). Equivalence could be established as the CI for the difference in LS Mean lay entirely within the pre-defined range of ±1 day. This positive result was supported by the analysis of secondary endpoints, which also revealed no clinical meaningful differences. Safety profiles were comparable between groups. No neutralizing antibodies against pegfilgrastim were identified.
Treatment equivalence in reducing the duration of chemotherapy induced neutropenia between RGB-02 and Neulasta® could be demonstrated. Similar efficacy and safety profiles of the once-per-cycle administration of RGB-02 and the pegfilgrastim reference were demonstrated.
The trial was registered prospectively, prior to study initiation. EudraCT number ( 2013-003166-14 ). The date of registration was 12 July, 2013.
使用重组人粒细胞集落刺激因子（G-CSF）治疗已被接受为预防化疗引起的中性粒细胞减少症的标准治疗方法。RGB-02（杰特贝林）是一种与聚乙二醇化 G-CSF（Neulasta®，安进）具有相似结构的生物类似药，具有缓释特性。这是一项随机、对照、双盲、多中心研究，旨在评估 RGB-02 在接受细胞毒性方案治疗的乳腺癌患者中的疗效和安全性。
239 名患有乳腺癌的女性患者被随机分配至 RGB-02（n=121）和参比产品（n=118）组。所有患者均接受多达 6 个周期的多西他赛/多柔比星化疗联合每周期 6mg 固定剂量的培非格司亭注射。主要终点是第 1 周期（双侧 95%CI）严重中性粒细胞减少症（ANC<0.5×10/L）的持续时间。次要终点包括第 2-4 周期严重中性粒细胞减少症的发生率和持续时间、发热性中性粒细胞减少症的发生率、ANC 恢复时间、ANC 最低点深度和安全性结果。
第 1 周期严重中性粒细胞减少症的平均持续时间为 1.7（RGB-02）和 1.6 天（参比），LS 均值差为 0.1 天（95%CI-0.2，0.4）。可以确定等效性，因为差异的 LS 均值 CI 完全包含在预先定义的±1 天范围内。这一阳性结果得到了次要终点分析的支持，该分析也显示出无临床意义的差异。两组的安全性特征相似。未发现针对培非格司亭的中和抗体。
可以证明 RGB-02 与 Neulasta®在减少化疗引起的中性粒细胞减少症持续时间方面具有治疗等效性。证明了 RGB-02 和培非格司亭参比药物每周期一次给药的疗效和安全性相似。
该试验在研究启动前进行了前瞻性注册。EudraCT 编号（2013-003166-14）。注册日期为 2013 年 7 月 12 日。
