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Safety and efficacy of alternating treatment with EP2006, a filgrastim biosimilar, and reference filgrastim: a phase III, randomised, double-blind clinical study in the prevention of severe neutropenia in patients with breast cancer receiving myelosuppressive chemotherapy.
Annals of Oncology ( IF 50.5 ) Pub Date : 2018-01-01 , DOI: 10.1093/annonc/mdx638
K Blackwell 1 , P Gascon 2 , A Krendyukov 3 , S Gattu 3 , Y Li 4 , N Harbeck 5
Affiliation  

Background In 2015, the biosimilar filgrastim EP2006 became the first biosimilar approved by the US Food and Drug Administration for commercial use in the United States, marketed as Zarxio® (Sandoz). This phase III randomised, double-blind registration study in patients with breast cancer receiving (neo)adjuvant myelosuppressive chemotherapy (TAC; docetaxel + doxorubicin + cyclophosphamide) compares reference filgrastim, Neupogen® (Amgen), with two groups receiving alternating treatment with reference and biosimilar every other cycle. Patients and methods A total of 218 patients receiving 5 µg/kg/day filgrastim over six chemotherapy cycles were randomised 1: 1: 1: 1 into four arms. Two arms received only one product, biosimilar or reference (unswitched), and two arms (switched) received alternating treatments every other cycle (biosimilar then reference or vice versa over six cycles). Since the switch occurred from cycle 2 onwards, this analysis compared pooled switched groups to the unswitched reference group for efficacy during cycles 2-6. Safety was also assessed. Non-inferiority in febrile neutropenia (FN) rates between groups for cycles 2-6 was shown if 95% were within a pre-defined margin of - 15%. Results A total of 109 patients switched treatment, and 52 patients received reference in all cycles. Baseline characteristics were similar between groups. The incidence of FN was 0% (reference) versus 3.4% (n = 3, switched) across cycles 2-6, with a difference of - 3.4% (95% confidence interval: -9.65% to 4.96%), showing non-inferiority. Infections occurred in 9.3% (switched) versus 9.9% (reference). Hospitalisation due to FN was low (one patient in cycle 6; switched). Adverse events related to filgrastim were reported in 42.1% (switched) versus 39.2% (reference) (all cycles). Musculoskeletal/connective tissue disorders related to filgrastim occurred in 35.5% (switched) versus 39.2% (reference) (all cycles), including bone pain (30.8% versus 33.3%). No neutralising antibodies were detected. Conclusions There were no clinically meaningful results regarding efficacy, safety or immunogenicity when switching from reference to biosimilar filgrastim/EP2006, or vice versa.

中文翻译:

使用EP2006,非格司亭生物仿制药和参比非格司亭交替治疗的安全性和有效性:一项接受骨髓抑制性化疗的乳腺癌患者预防重度中性粒细胞减少的III期随机双盲临床研究。

背景技术2015年,仿制药非格司亭EP2006成为美国食品和药物管理局批准的首个在美国商业使用的仿制药,商品名为Zarxio®(Sandoz)。这项针对接受(新)辅助骨髓抑制化疗(TAC;多西紫杉醇+阿霉素+环磷酰胺)的乳腺癌患者的III期随机,双盲注册研究比较了参比非司亭Neupogen®(Amgen),两组分别接受了参比和生物仿制药每隔一个周期。患者和方法总共218名患者在六个化疗周期中接受5 µg / kg /天的非格司亭治疗,按1:1:1:1的比例随机分为四组。两个部门仅收到一种产品,生物仿制药或参考药品(未转换),并且两个手臂(切换)每隔一个周期接受交替治疗(在六个周期内,先进行生物仿制药再进行参考治疗,反之亦然)。由于转换是从第2周期开始发生的,因此本分析比较了第2-6周期中合并的转换组与未转换的参考组的功效。还评估了安全性。如果95%的预定义范围在-15%以内,则表明2-6个周期各组之间的发热性中性粒细胞减少症(FN)率无差异。结果共有109例患者转用治疗,其中52例患者在所有周期中均接受了参考。各组之间的基线特征相似。在2-6个周期中,FN的发生率为0%(参考),而3.4%(n = 3,切换)发生率,差异为-3.4%(95%置信区间:-9.65%至4.96%),自卑。感染发生率为9.3%(转换后),而感染发生率为9%。9%(参考)。FN导致的住院率低(第6周期一名患者;已切换)。与非格司亭相关的不良事件报道为42.1%(转换),而报告的非参考文献为39.2%(参考)(所有周期)。与非格司亭相关的肌肉骨骼/结缔组织疾病发生率为35.5%(转换),而发生率为39.2%(参考)(所有周期),包括骨痛(分别为30.8%和33.3%)。未检测到中和抗体。结论当从参比仿制药filgrastim / EP2006转换为药效学,安全性或免疫原性时,没有临床上有意义的结果,反之亦然。5%(转换)对39.2%(参考)(所有周期),包括骨痛(30.8%对33.3%)。未检测到中和抗体。结论当从参比仿制药filgrastim / EP2006转换为药效学,安全性或免疫原性时,没有临床上有意义的结果,反之亦然。5%(转换)对39.2%(参考)(所有周期),包括骨痛(30.8%对33.3%)。未检测到中和抗体。结论当从参比仿制药filgrastim / EP2006转换为药效学,安全性或免疫原性时,没有临床上有意义的结果,反之亦然。
更新日期:2018-01-26
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