Department of Medical Oncology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Internal, Faculty of Medicine, Islamic Azad University, Yazd, Iran.
Clin Ther. 2020 May;42(5):848-859. doi: 10.1016/j.clinthera.2020.03.009. Epub 2020 Apr 22.
The purpose of this study was to compare the efficacy and safety of a proposed bevacizumab biosimilar to those of the reference product in patients with metastatic colorectal cancer (mCRC).
This Phase III, multicenter, randomized, double-blind (patient- and assessor-blind), active-controlled, 2-armed, parallel-group, noninferiority trial was conducted in patients with histologically verified colorectal cancer with evidence of at least 1 metastasis. Patients with mCRC were randomized 2:1 to receive 5 mg/kg IV of either study drug plus FOLFIRI-3 (with repeated irinotecan 100 mg/m 60-min infusion on day 3) or the reference drug plus FOLFIRI-3 every 2 weeks for 1 year. Progression-free survival (PFS) was the primary end point, and overall survival, objective response rate, and time to treatment failure as well as safety and immunogenicity were secondary end points. The population assessable for PFS was per protocol, and the intention-to-treat population was used for sensitivity analysis. Safety was assessed based on reports of adverse events, laboratory test results, and vital sign measurements.
A total of 126 patients were enrolled; PFS values in the biosimilar and reference arms were 232 days (7.7 months) and 210 days (7 months), respectively (P = 0.47). The hazard ratio of the biosimilar arm versus the reference arm was 0.79 in the per-protocol population (90% CI, 0.46-1.35; P = 0.47). The upper limit for the 2-sided 90% CI was lower than the margin of 1.44, indicating that the biosimilar drug was noninferior to the reference drug. The hazard ratio for overall survival in the intent-to-treat population was 0.99 (95% CI, 0.55-1.80; P = 0.99). The difference between other efficacy end points among the groups was not statistically significant. No significant difference was observed in the comparison of the two arms for safety. The antidrug antibody was positive in 1 patient in each arm.
The proposed biosimilar BE1040V was noninferior to the reference product in terms of efficacy in the treatment of mCRC, and tolerability was comparable between the 2 drugs. ClinicalTrials.gov identifier: NCT03288987.
本研究旨在比较一种拟议的贝伐珠单抗生物类似药与参照产品在转移性结直肠癌（mCRC）患者中的疗效和安全性。
这是一项 III 期、多中心、随机、双盲（患者和评估者双盲）、活性对照、2 臂、平行组、非劣效性试验，纳入了组织学证实的结直肠癌患者，这些患者有至少 1 处转移灶的证据。mCRC 患者以 2:1 的比例随机分配，接受 5mg/kg 静脉注射研究药物加 FOLFIRI-3（第 3 天重复伊立替康 100mg/m 60 分钟输注）或参照药物加 FOLFIRI-3，每 2 周 1 次，持续 1 年。无进展生存期（PFS）是主要终点，总生存期、客观缓解率、治疗失败时间以及安全性和免疫原性是次要终点。可评估 PFS 的人群为方案人群，意向治疗人群用于敏感性分析。安全性基于不良事件报告、实验室检测结果和生命体征测量值进行评估。
共纳入 126 例患者；生物类似药组和参照药组的 PFS 值分别为 232 天（7.7 个月）和 210 天（7 个月）（P=0.47）。方案人群中生物类似药组与参照药组的风险比为 0.79（90%CI，0.46-1.35；P=0.47）。双侧 90%CI 的上限低于 1.44 的边界，表明生物类似药不劣于参照药。意向治疗人群的总生存期风险比为 0.99（95%CI，0.55-1.80；P=0.99）。组间其他疗效终点的差异无统计学意义。两组间安全性比较无显著差异。每个臂的抗药物抗体均为阳性。
在治疗 mCRC 方面，拟议的贝伐珠单抗生物类似药 BE1040V 与参照产品在疗效方面非劣效，两种药物的耐受性相当。临床试验.gov 标识符：NCT03288987。
