Bevacizumab Plus Atezolizumab After Progression on Atezolizumab Monotherapy in Pretreated Patients With NSCLC: An Open-Label, Two-Stage, Phase 2 Trial
Bevacizumab Plus Atezolizumab After Progression on Atezolizumab Monotherapy in Pretreated Patients With NSCLC: An Open-Label, Two-Stage, Phase 2 Trial
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DOI：
10.1016/j.jtho.2022.04.001
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发表时间：
2022-07-01
影响因子：
20.4
通讯作者：
Ahn, Myung-Ju
中科院分区：
文献类型：
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作者：
Lee, Jiyun;Koh, Jiae;Ahn, Myung-Ju
简介：血管内皮生长因子促进免疫抑制肿瘤微环境，可通过抗血管生成治疗逆转。这个两个阶段，2期研究的目的是确定在atezolizumab单药治疗后疾病进展的转移性NSCLC患者中加入贝伐单抗的治疗效果。方法：免疫检查点载体初治的NSCLC患者，没有EGFR或ALK改变，其疾病进展后，至少有一行铂类化疗是合格的。患者接受atezolizumab 1200 mg，每3周一次，直至放射学进展（I期）。然后，贝伐珠单抗15 mg/kg与atezolizumab 1200 mg联合给药，每3周一次（II期）。主要终点是局限于II期的疾病控制率（DCR）。结果：共有42例和24例患者分别入选I期和II期。大多数患者程序性死亡配体-1表达阴性（71.4%），接受一线或二线治疗（95.2%）。在I期，患者的DCR为35.7%（95%置信区间[CI]：21.6-52.0）。在II期，24例患者中分别有3例（12.5%）和18例（75.0%）部分缓解和疾病稳定，DCR为87.5%（95% CI：67.697.3）。对于入组II期的24例患者，中位无进展生存期为5.6（95% CI：4.1-7.1）个月，总生存期为14.0（95% CI：10.7-17.4）个月。25%的II期患者发生了治疗相关不良事件，但均为1级或2级。结论：贝伐单抗联合atezolizumab治疗atezolizumab单药治疗后疾病进展的转移性NSCLC患者具有良好的抗肿瘤活性和耐受性。(C)2022年国际肺癌研究协会。爱思唯尔公司出版All rights reserved.
Introduction: Vascular endothelial growth factor promotes an immunosuppressive tumor microenvironment that can be reverted by an antiangiogenic therapy. This two-stage, phase 2 study aimed to determine the treatment efficacy of adding bevacizumab to atezolizumab in patients with metastatic NSCLC whose disease had progressed after atezolizumab monotherapy.Methods: Immune checkpoint inhibitor-naive patients with NSCLC, without EGFR or ALK alterations, whose disease progressed after at least one line of platinum-based chemotherapy were eligible. The patients received atezolizumab 1200 mg once every 3 weeks until radiographic progression (stage I). Then, bevacizumab 15 mg/kg was combined with atezolizumab 1200 mg once every 3 weeks (stage II). The primary end point was the disease control rate (DCR) confined to stage II.Results: A total of 42 and 24 patients were enrolled in stages I and II, respectively. Most patients had negative programmed death ligand-1 expression (71.4%) and received one or two lines of therapy (95.2%). In stage I, patients achieved a DCR of 35.7% (95% confidence interval [CI]: 21.6-52.0). In stage II, three (12.5%) and 18 (75.0%) of 24 patients had partial response and stable disease, respectively, leading to a DCR of 87.5% (95% CI: 67.697.3). For 24 patients enrolled in stage II, the median progression-free survival was 5.6 (95% CI: 4.1-7.1) months and the overall survival was 14.0 (95% CI: 10.7-17.4) months. Treatment-related adverse events occurred in 25% of the patients in stage II, but all were of grade 1 or 2.Conclusions: Combination of bevacizumab plus atezolizumab for patients with metastatic NSCLC whose disease had progressed after atezolizumab monotherapy was found to have a promising antitumor activity with good tolerability. (C) 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.