Meharry Medical College, 1005 Dr. D.B. Todd Jr. Blvd, Nashville, TN, 37208-3501, USA.
Semmelweis University, Cancer Center, Tömő u. 25-29, Budapest, 1083, Hungary.
Br J Cancer. 2018 Aug;119(3):266-273. doi: 10.1038/s41416-018-0147-1. Epub 2018 Jul 13.
This randomised, double-blind study compared pharmacokinetics, efficacy, safety and immunogenicity of PF-05280014 (potential trastuzumab biosimilar) and trastuzumab reference product (Herceptin) sourced from the European Union (trastuzumab-EU) as neoadjuvant treatment for operable human epidermal growth factor receptor 2 (HER2)-positive breast cancer.
Patients (N = 226), stratified by primary tumour size and hormone receptor status, were randomised 1:1 to PF-05280014 or trastuzumab-EU (8 mg/kg loading dose; 6 mg/kg thereafter), each with docetaxel and carboplatin, every 3 weeks for six treatment cycles. Primary endpoint was percentage of patients with trough plasma concentration (C) >20 μg/ml at Cycle 5 (Cycle 6 predose). Efficacy endpoints included pathological complete response and objective response rate. Non-inferiority of PF-05280014 to trastuzumab-EU was declared if the lower limit of the 95% confidence interval for the stratified difference between groups in the percentage of patients with Cycle 5 C >20 μg/ml was above the prespecified non-inferiority margin of - 12.5%.
For PF-05280014 vs trastuzumab-EU patients, respectively, 92.1% vs 93.3% had Cycle 5 C >20 μg/ml; the lower limit of the 95% confidence interval (- 8.02%, 6.49%) for the stratified difference between groups was above the non-inferiority margin (- 12.5%). Pathological complete response (47.0% vs 50.0%) and central radiology review-assessed objective response (88.1% vs 82.0%) rates were comparable. Incidence of all-causality, grade 3-4 treatment-emergent adverse events was 38.1% vs 45.5%; antidrug antibody rates were 0% vs 0.89%.
PF-05280014 demonstrated non-inferior pharmacokinetics and comparable efficacy, safety and immunogenicity to trastuzumab-EU in patients with operable HER2-positive breast cancer receiving neoadjuvant chemotherapy.
这项随机、双盲研究比较了 PF-05280014（潜在曲妥珠单抗生物类似药）和曲妥珠单抗参考产品（来自欧盟的赫赛汀）作为可手术人表皮生长因子受体 2（HER2）阳性乳腺癌新辅助治疗的药代动力学、疗效、安全性和免疫原性。
患者（N=226）按原发肿瘤大小和激素受体状态分层，按 1:1 随机分配至 PF-05280014 或曲妥珠单抗-EU（8mg/kg 负荷剂量；此后 6mg/kg），均与多西他赛和卡铂联合使用，每 3 周为一个治疗周期，共 6 个周期。主要终点为第 5 周期（第 6 周期给药前）时患者的谷血浆浓度（C）>20μg/ml 的百分比。疗效终点包括病理完全缓解率和客观缓解率。如果分层组间第 5 周期 C>20μg/ml 的患者百分比的组间差异 95%置信区间的下限大于预设的非劣效性边界（-12.5%），则宣布 PF-05280014 不劣于曲妥珠单抗-EU。
对于 PF-05280014 与曲妥珠单抗-EU 患者，分别有 92.1%和 93.3%的患者第 5 周期 C>20μg/ml；分层组间差异的 95%置信区间下限（-8.02%，6.49%）大于非劣效性边界（-12.5%）。病理完全缓解率（47.0%比 50.0%）和中央放射学评估的客观缓解率（88.1%比 82.0%）相似。所有病因、3-4 级治疗相关不良事件的发生率分别为 38.1%和 45.5%；抗药物抗体发生率分别为 0%和 0.89%。
在接受新辅助化疗的可手术 HER2 阳性乳腺癌患者中，PF-05280014 表现出与曲妥珠单抗-EU 非劣效的药代动力学，且疗效、安全性和免疫原性相当。
