General Hospital of Chest Diseases of Athens "Sotiria", Athens, Greece.
Mátrai Gyógyintézet-Bronchológia, Heves, Hungary.
BioDrugs. 2021 Jul;35(4):417-428. doi: 10.1007/s40259-021-00489-4. Epub 2021 Jul 15.
Bevacizumab is an antiangiogenic recombinant humanized monoclonal antibody that inhibits tumor growth. FKB238, a bevacizumab biosimilar, has analytical pharmacokinetic and safety profiles similar to those of bevacizumab.
This phase III trial (NCT02810457) compared the efficacy and safety of FKB238 with that of bevacizumab in patients with advanced/recurrent non-squamous non-small-cell lung cancer (non-sq-NSCLC).
This global, multicenter, double-blind, parallel, randomized, comparative clinical trial enrolled and randomized patients with advanced/recurrent non-sq-NSCLC to receive intravenous infusions of either FKB238 15 mg/kg or bevacizumab 15 mg/kg. All patients received intravenous infusions of paclitaxel 200 mg/m and carboplatin (area under the curve 6.0) immediately prior to investigational products for 4-6 cycles. FKB238 and bevacizumab were administered on day 1 of each 21-day cycle until objective progressive disease by RECIST version 1.1 or other discontinuation criteria were met. The primary efficacy endpoint was overall response rate (ORR), including complete and partial response and based on blinded independent central review assessment. Other efficacy determinations included progression-free survival (PFS), overall survival (OS), and immunogenicity. Adverse events and severity were reported.
The ORR for the intent-to-treat (ITT) population (N = 731) was 51.6% in the FKB238 arm (N = 364) and 53.7% in the bevacizumab arm (N = 367). The FKB238:bevacizumab ORR ratio (ITT population) was 0.96 (90% confidence interval [CI] 0.86-1.08), and the difference in ORR (per-protocol set) between FKB238 and bevacizumab was - 0.02 (95% CI - 0.09 to 0.06). Both CIs fell within the prespecified equivalence margins. Estimated median PFS was 7.72 and 7.62 months in the FKB238 and bevacizumab arms, respectively (hazard ratio 0.97; 95% CI 0.82-1.16). Treatment-emergent adverse events (TEAEs) were reported for 94.2% and 95.1% of patients in the FKB238 and bevacizumab arms, respectively. Grade 3 or higher TEAEs were reported for 53.6% and 55.5% of patients in the FKB238 and bevacizumab arms, respectively. Serious TEAEs were reported for 25.1% and 26.0% of patients treated with FKB238 and bevacizumab, respectively.
Efficacy equivalence was demonstrated between the two drugs, and safety profiles were similar. There were no meaningful differences in efficacy and safety between FKB238 or bevacizumab in patients with non-sq-NSCLC.
NCT02810457.
贝伐珠单抗是一种抗血管生成的重组人源化单克隆抗体，可抑制肿瘤生长。FKB238 是一种贝伐珠单抗生物类似药，其分析药代动力学和安全性特征与贝伐珠单抗相似。
本 III 期试验（NCT02810457）比较了 FKB238 与贝伐珠单抗在晚期/复发性非鳞状非小细胞肺癌（非鳞状非小细胞肺癌）患者中的疗效和安全性。
这项全球性、多中心、双盲、平行、随机、对照临床试验纳入了晚期/复发性非鳞状非小细胞肺癌患者，并将其随机分为 FKB238 15mg/kg 或贝伐珠单抗 15mg/kg 静脉输注组。所有患者均在研究产品前接受紫杉醇 200mg/m2 和卡铂（曲线下面积 6.0）静脉输注，每 21 天为一个周期，共 4-6 个周期。FKB238 和贝伐珠单抗在每个 21 天周期的第 1 天给药，直至根据 RECIST 版本 1.1 或其他停药标准出现客观疾病进展。主要疗效终点为总缓解率（ORR），包括完全缓解和部分缓解，基于盲法独立中心评估。其他疗效评估包括无进展生存期（PFS）、总生存期（OS）和免疫原性。报告了不良事件和严重程度。
意向治疗（ITT）人群（N=731）的 ORR 为 FKB238 组（N=364）51.6%，贝伐珠单抗组（N=367）53.7%。FKB238:贝伐珠单抗 ORR 比值（ITT 人群）为 0.96（90%置信区间 [CI] 0.86-1.08），FKB238 和贝伐珠单抗之间的 ORR 差异（方案设定）为-0.02（95%CI -0.09 至 0.06）。两个 CI 均落在预设的等效区间内。FKB238 和贝伐珠单抗组的中位估计 PFS 分别为 7.72 和 7.62 个月（风险比 0.97；95%CI 0.82-1.16）。FKB238 和贝伐珠单抗组分别有 94.2%和 95.1%的患者报告了治疗出现的不良事件（TEAEs）。FKB238 和贝伐珠单抗组分别有 53.6%和 55.5%的患者报告了 3 级或更高级别的 TEAEs。分别有 25.1%和 26.0%接受 FKB238 和贝伐珠单抗治疗的患者报告了严重 TEAEs。
两种药物的疗效等效性得到了证实，安全性特征相似。在非鳞状非小细胞肺癌患者中，FKB238 或贝伐珠单抗的疗效和安全性没有明显差异。
NCT02810457。
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