Lu S, Qin S, Zhou Z, Chen J, Gu K, Sun P, Pan Y, Yu G, Ma K, Shi J, Sun Y, Yang L, Chen P, Liu A, He J
Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Cancer Center, Nanjing Jinling Hospital, Nanjing, China.
J Cancer Res Clin Oncol. 2023 Aug;149(9):5907-5914. doi: 10.1007/s00432-022-04563-4. Epub 2023 Jan 3.
Bevacizumab (Avastin) is a monoclonal antibody targeting the vascular endothelial growth factor (VEGF). Used alone or in combination with chemotherapy and/or immunotherapy, Avastin has shown promising efficacy in many cancers. This study compared the efficacy and safety of TAB008 with Avastin sourced from the EU (bevacizumab-EU), in patients with non-squamous non-small cell lung cancer (nsNSCLC).
In this randomized, double-blind, multicenter, phase III similarity study, treatment naïve for metastatic lung cancer., EGFR wild-type, locally advanced, metastatic, or recurrent non-squamous, non-small cell, lung cancer (nsNSCLC) patients were enrolled and randomized (1:1) into TAB008 or Avastin groups. Patients received TAB008 or Avastin 15 mg/kg intravenously plus paclitaxel/carboplatin for 4-6 cycles followed by TAB008 or Avastin 7.5 mg/kg until disease progression, unacceptable toxicity or death. The primary endpoint compared the objective response rate (ORR) within 6 cycles as read by an independent radiological review committee (IRRC). Secondary endpoints compared disease control rate (DCR) Within 6 cycles, duration of response (DoR), progression-free survival (PFS), a year overall survival rate (OSR), overall survival (OS), safety, immunogenicity, and steady-state pharmacokinetics.
A total of 549 nsNSCLC patients were enrolled (277 in TAB008 group and 272 in Avastin group). In the full analysis set, ORRs were 55.957% for TAB008 and 55.720% for Avastin, and the ORR ratio was 1 (90% CI 0.89-1.14), well within the predefined equivalence margin of 0.75-1.33. No significant differences were found in DCR within 6 cycles (95.703% vs 95.367%, p = 0.8536), DoR (8.17 vs 7.3 months, p = 0.3526), PFS (9.10 vs. 7.97 months, p = 0.9457), 1 year overall survival rate (66.2% vs 68%, p = 0.6793), or OS (20.4 vs 17.6 months, p = 0.6549). Serious adverse events (SAEs) occurred in 37.55% (104/277) of patients in the TAB008 group and 34.32% (93/271) in the Avastin group. Anti-drug antibodies were reported in 3 of 277 (1.08%) TAB008 patients, and 5 of 271 (1.85%) Avastin patients, neutralizing antibody (Nab) was positive in 1 patient on Avastin, which became negative upon follow-up. The steady-state trough concentrations (C) were 106.13 μg/mL in TAB008 group and 96.03 μg/mL in Avastin groups, with the treatment group ratio of LS geometric means fully contained within the bioequivalence limits of 80.00-125.00% (90% CI was 101.74-120.05%).
TAB008 is similar to Avastin in terms of efficacy, safety, and pharmacokinetic parameters, with comparable immunogenicity.
ClinicalTrials.gov number; NCT05427305.
贝伐单抗（阿瓦斯汀）是一种靶向血管内皮生长因子（VEGF）的单克隆抗体。单独使用或与化疗和/或免疫疗法联合使用时，阿瓦斯汀在许多癌症中已显示出有前景的疗效。本研究比较了TAB008与源自欧盟的阿瓦斯汀（贝伐单抗 - 欧盟）在非鳞状非小细胞肺癌（nsNSCLC）患者中的疗效和安全性。
在这项随机、双盲、多中心、III期相似性研究中，纳入了初治的转移性肺癌、EGFR野生型、局部晚期、转移性或复发性非鳞状、非小细胞肺癌（nsNSCLC）患者，并将其随机（1:1）分为TAB008组或阿瓦斯汀组。患者接受TAB008或阿瓦斯汀15mg/kg静脉注射加紫杉醇/卡铂治疗4 - 6个周期，随后接受TAB008或阿瓦斯汀7.5mg/kg，直至疾病进展、出现不可接受的毒性或死亡。主要终点是由独立放射学审查委员会（IRRC）读取的6个周期内的客观缓解率（ORR）。次要终点包括比较6个周期内的疾病控制率（DCR）、缓解持续时间（DoR）、无进展生存期（PFS）、一年总生存率（OSR）、总生存期（OS）、安全性、免疫原性和稳态药代动力学。
总共纳入了549例nsNSCLC患者（TAB008组277例，阿瓦斯汀组272例）。在全分析集中，TAB008的ORR为55.957%，阿瓦斯汀的ORR为55.720%，ORR比值为1（90%CI 0.89 - 1.14），完全在预先定义的等效界值0.75 - 1.33范围内。6个周期内的DCR（95.703%对95.367%，p = 0.8536）、DoR（8.17对(7.3)个月，p = 0.3526）、PFS（9.10对7.97个月，p = 0.9457）、一年总生存率（66.2%对68%，p = 0.6793）或OS（20.4对17.6个月，p = 0.6549）均未发现显著差异。严重不良事件（SAEs）在TAB008组37.55%（104/277）的患者中发生，在阿瓦斯汀组34.32%（93/271）的患者中发生。277例TAB008患者中有3例（1.08%）报告了抗药抗体，271例阿瓦斯汀患者中有5例（1.85%）报告了抗药抗体，1例阿瓦斯汀患者的中和抗体（Nab）呈阳性，随访时转为阴性。TAB008组的稳态谷浓度（C）为106.13μg/mL，阿瓦斯汀组为96.03μg/mL，治疗组的LS几何均值比值完全在生物等效性限度80.00 - 125.00%内（90%CI为101.74 - 120.05%）。
TAB008在疗效、安全性和药代动力学参数方面与阿瓦斯汀相似，免疫原性相当。
ClinicalTrials.gov编号；NCT05427305 。
