Kim Edward S, Balser Sigrid, Rohr Klaus B, Lohmann Ragna, Liedert Bernd, Schliephake Dorothee
City of Hope National Medical Center, Los Angeles, California.
Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
JTO Clin Res Rep. 2021 Oct 28;3(1):100248. doi: 10.1016/j.jtocrr.2021.100248. eCollection 2022 Jan.
Biological therapies such as bevacizumab have improved survival in patients with NSCLC. This study was conducted to confirm the equivalent efficacy of the biosimilar candidate BI 695502 to the bevacizumab reference product (RP).
In this phase 3, multicenter, randomized, double-blind trial of adult patients with recurrent or metastatic NSCLC received up to 18 weeks of induction treatment with BI 695502 or bevacizumab RP 15 mg/kg plus paclitaxel and carboplatin. Subsequent maintenance therapy comprised BI 695502 or bevacizumab RP monotherapy until disease progression or unacceptable toxicity. The primary end point was the best overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 assessed by central imaging review, until 18 weeks after the start of treatment.
In total, 671 patients were randomized at one-to-one ratio to BI 695502 or bevacizumab RP, of whom 335 and 328, respectively, received treatment. Of these, 228 (68.1%) and 256 (78.0%), respectively, proceeded to maintenance monotherapy. A manufacturing issue led to a small number of patients treated with BI 695502 switching to bevacizumab RP late in the study. The primary end point, best ORR, was 54.0% in the BI 695502 group and 63.1% in the bevacizumab RP group. The 90% confidence interval for the between-group ratio of best ORR (0.770 to 0.951) was within the prespecified range for equivalence (0.736-1.359). Adverse events were class-related and similar between the two treatment arms.
This study revealed equivalent ORR after 18 weeks of treatment with BI 695502 or bevacizumab RP, with similar adverse event profiles.
贝伐单抗等生物疗法已改善了非小细胞肺癌（NSCLC）患者的生存率。本研究旨在证实生物类似药候选药物BI 695502与贝伐单抗参比产品（RP）的等效疗效。
在这项针对复发或转移性NSCLC成年患者的3期多中心随机双盲试验中，患者接受了长达18周的诱导治疗，使用BI 695502或贝伐单抗RP 15 mg/kg加紫杉醇和卡铂。随后的维持治疗包括BI 695502或贝伐单抗RP单药治疗，直至疾病进展或出现不可接受的毒性。主要终点是根据实体瘤疗效评价标准1.1版，通过中心影像评估的最佳总体缓解率（ORR），直至治疗开始后18周。
总共671例患者按1:1比例随机分配至BI 695502或贝伐单抗RP组，其中分别有335例和328例接受了治疗。其中，分别有228例（68.1%）和256例（78.0%）进入维持单药治疗。一个生产问题导致少数接受BI 695502治疗的患者在研究后期改用贝伐单抗RP。主要终点，即最佳ORR，在BI 695502组中为54.0%，在贝伐单抗RP组中为63.1%。最佳ORR组间比值的90%置信区间（0.770至0.951）在预先设定的等效范围内（0.736 - 1.359）。不良事件与类别相关，两个治疗组相似。
本研究显示，使用BI 695502或贝伐单抗RP治疗18周后，ORR相当，不良事件谱相似。
