一个随机的II期研究，对于非小细胞肺癌携带EGFR突变的化疗初诊患者，评估afatinib单独或与bevacizumab联合治疗的疗效。
A randomized phase II study of afatinib alone or combined with bevacizumab for treating chemo-naïve patients with non-small cell lung cancer harboring EGFR mutations.
发表日期：2023 Aug 19
作者：
Takashi Ninomiya, Nobuhisa Ishikawa, Toshiyuki Kozuki, Shoichi Kuyama, Koji Inoue, Toshihide Yokoyama, Nobuhiro Kanaji, Masayuki Yasugi, Takuo Shibayama, Keisuke Aoe, Nobuaki Ochi, Kazunori Fujitaka, Masahiro Kodani, Yutaka Ueda, Kazuhiko Watanabe, Akihiro Bessho, Keisuke Sugimoto, Isao Oze, Katsuyuki Hotta, Katsuyuki Kiura
来源：
LUNG CANCER
摘要：
在第一代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）基础上加入贝伐单抗延长了进展无瘤生存期（PFS），但现有有关第二代EGFR-TKI的数据有限。AfaBev-CS是一个随机的2期试验，比较了阿法替尼加贝伐单抗与单独使用阿法替尼作为一线治疗。未经治疗的非鳞状非小细胞肺癌（NSCLC）携带EGFR突变（Del19或L858R）的患者被纳入研究，并随机分配到阿法替尼（30 mg）加贝伐单抗（AfaBev组）或阿法替尼（40 mg）单药治疗（Afa组）。主要终点为PFS。在Afa组的中位PFS假定为12个月和AfaBev组的HR为0.6的情况下，研究功效为50%以上。自2017年8月至2019年9月，共有100名患者入组。两组之间PFS无显著差异。AfaBev组的中位PFS为16.3个月，Afa组为16.1个月，HR为0.865（95%可信区间[CI]，0.539至1.388；p = 0.55）。在总生存方面，两组也没有显著差异（HR，0.84；95% CI，0.39至1.83；p = 0.67）。AfaBev组的整体缓解率为82.6%，Afa组为76.6%（p = 0.61）。AfaBev组常见的≥3级不良事件包括腹泻、高血压、痤疮样皮疹、甲床炎和口腔炎。该研究未能证明AfaBev在未经治疗的EGFR突变NSCLC患者中改善PFS的疗效。版权所有 © 2023 Elsevier B.V. 保留所有权利。
Adding bevacizumab to first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) prolonged the progression-free survival (PFS), but limited data are available for second-generation EGFR-TKIs. AfaBev-CS is a randomized, phase II trial comparing afatinib plus bevacizumab and afatinib alone as first-line treatment.Untreated patients with non-squamous non-small cell lung cancer (NSCLC) harboring EGFR mutations (Del19 or L858R) were enrolled and randomly assigned to receive either afatinib (30 mg) plus bevacizumab (AfaBev group) or afatinib (40 mg) monotherapy (Afa group). The primary endpoint was PFS. The power was >50% under the assumptions of a median PFS of 12 months for the Afa group and hazard ratio (HR) of 0.6 for the AfaBev group.Between August 2017 and September 2019, 100 patients were enrolled. There was no significant difference in PFS between the groups. The median PFS was 16.3 and 16.1 months for the AfaBev and Afa groups, respectively, with an HR of 0.865 (95% confidence interval [CI], 0.539 to 1.388; p = 0.55). In terms of overall survival, there was no significant difference between the groups (HR, 0.84; 95% CI, 0.39 to 1.83; p = 0.67). The overall response rate was 82.6% and 76.6% in the AfaBev and Afa groups, respectively (p = 0.61). Grade ≥ 3 diarrhea, hypertension, acneiform rash, paronychia, and stomatitis were frequently observed in the AfaBev group.This study failed to show efficacy of AfaBev over Afa for improving PFS in untreated patients with EGFR-mutated NSCLC.Copyright © 2023 Elsevier B.V. All rights reserved.