PF-06439535 (a Bevacizumab Biosimilar) Compared with Reference Bevacizumab (Avastin), Both Plus Paclitaxel and Carboplatin, as First-Line Treatment for Advanced Non-Squamous Non-Small-Cell Lung Cancer: A Randomized, Double-Blind Study
PF-06439535 (a Bevacizumab Biosimilar) Compared with Reference Bevacizumab (Avastin), Both Plus Paclitaxel and Carboplatin, as First-Line Treatment for Advanced Non-Squamous Non-Small-Cell Lung Cancer: A Randomized, Double-Blind Study
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DOI：
10.1007/s40259-019-00363-4
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发表时间：
2019-10-01
期刊：
影响因子：
6.8
通讯作者：
Kasahara, Kazuo
中科院分区：
文献类型：
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作者：
Reinmuth, Niels;Bryl, Maciej;Kasahara, Kazuo
背景PF-06439535是一种贝伐珠单抗生物类似药。我们旨在比较PF-06439535与来自欧盟的参比贝伐珠单抗（安维汀）（贝伐珠单抗-EU）（均与紫杉醇和卡铂联合）一线治疗晚期非鳞状非小细胞肺癌（NSCLC）的疗效和安全性。方法在这项双盲、平行组研究中，我们从27个国家的159个中心招募了患者。受试者以1：1的比例随机分配，在每个21天周期的第1天接受PF-06439535+紫杉醇和卡铂或贝伐珠单抗-EU+紫杉醇和卡铂治疗，持续4-6个周期，随后接受PF-06439535或贝伐珠单抗-EU盲态单药治疗，直至疾病进展、不可接受的毒性、撤回知情同意或研究结束。随机化按地区、性别和吸烟史分层。主要终点是根据RECIST 1.1的客观缓解率（ORR），基于第19周达到的缓解并在第25周确认。结果2015年5月21日至2016年11月14日期间，719例患者被随机分配至PF-06439535组（n = 358）或贝伐珠单抗-EU组（n = 361）。截至主要终点分析的数据截止日期（2017年5月8日），PF-06439535组45.3%（95%置信区间[CI] 40.01-50.57）的患者和贝伐珠单抗-EU组44.6%（95% CI 39.40-49.89）的患者在第19周达到客观缓解，并在第25周得到证实。未分层的ORR风险比为1.015（95% CI 0.863-1.193; 90% CI 0.886-1.163），未分层的ORR风险差异为0.653%（95% CI - 6.608 - 7.908）;所有3个CI均在预先规定的等效性界值范围内。使用研究完成后（2017年12月22日）的最终数据，未观察到组间无进展生存期或总生存期的显著差异。最常报告的3级或3级以上治疗后出现的不良事件为高血压、中性粒细胞减少症和贫血。治疗组间的安全性、药代动力学或免疫原性无具有临床意义的差异。结论在晚期非鳞状NSCLC患者中，PF-06439535与贝伐珠单抗-EU的疗效相似。两种治疗的安全性特征相当。资助辉瑞。
Background PF-06439535 is a bevacizumab biosimilar. We aimed to compare the efficacy and safety of PF-06439535 with that of reference bevacizumab (Avastin) sourced from the EU (bevacizumab-EU), each with paclitaxel and carboplatin, in the first-line treatment of advanced non-squamous non-small-cell lung cancer (NSCLC). Methods In this double-blind, parallel-group study, we recruited patients from 159 centers in 27 countries. Participants were randomized 1:1 to receive PF-06439535 plus paclitaxel and carboplatin or bevacizumab-EU plus paclitaxel and carboplatin on day 1 of each 21-day cycle for 4-6 cycles, followed by blinded monotherapy with PF-06439535 or bevacizumab-EU until disease progression, unacceptable toxicity, withdrawal of consent, or the end of the study. Randomization was stratified by region, sex, and smoking history. The primary endpoint was objective response rate (ORR) in accordance with RECIST 1.1, based on responses achieved by week 19 and confirmed by week 25. Results Between 21 May 2015 and 14 November 2016, 719 patients were randomized to the PF-06439535 group (n = 358) or the bevacizumab-EU group (n = 361). As of data cutoff for analysis of the primary endpoint (8 May 2017), 45.3% (95% confidence interval [CI] 40.01-50.57) of patients in the PF-06439535 group and 44.6% (95% CI 39.40-49.89) of patients in the bevacizumab-EU group achieved an objective response by week 19 that was confirmed by week 25. The unstratified ORR risk ratio was 1.015 (95% CI 0.863-1.193; 90% CI 0.886-1.163), and the unstratified ORR risk difference was 0.653% (95% CI - 6.608 to 7.908); all three CIs fell within pre-specified equivalence margins. Using final data after study completion (22 December 2017), no notable differences in progression-free survival or overall survival were observed between the groups. The most frequently reported grade 3 or higher treatment-emergent adverse events were hypertension, neutropenia, and anemia. There were no clinically meaningful differences in safety, pharmacokinetics, or immunogenicity across treatment groups. Conclusion Among patients with advanced non-squamous NSCLC, PF-06439535 demonstrated similarity to bevacizumab-EU in terms of efficacy. Safety profiles for the two treatments were comparable. Funding Pfizer.