Kong Lingping, Peng Lina, Yang Xue, Ma Qing, Zhang Linlin, Liu Xia, Zhong Diansheng, Meng Fanlu
Department of Medical Oncology, Tianjin Medical University General Hospital, Tianjin, China.
Front Oncol. 2025 Jun 4;15:1595812. doi: 10.3389/fonc.2025.1595812. eCollection 2025.
Aumolertinib is a novel third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) with proven efficacy and safety for untreated non-small-cell lung cancer (NSCLC) patients with EGFR sensitizing mutations (EGFRm) in China. The progression-free survival (PFS) improvement of the combination of first-generation EGFR-TKIs and bevacizumab was confirmed by CTONG1509, JO25567, and NEJ026 studies, however, the effect of third-generation EGFR-TKIs plus bevacizumab remains under debate. This study aimed to investigate the efficacy and safety of aumolertinib plus bevacizumab in untreated EGFRm advanced NSCLC.
We conducted a phase II single-arm prospective clinical trial for advanced EGFRm NSCLC treated with aumolertinib combined with bevacizumab. Treatment continued until disease progression, occurrence of unacceptable toxicities, or the patient withdrew consent. The study was stratified according to sex, smoking history, stage, EGFR mutation status, and central nervous system (CNS) metastasis. The primary endpoint was the 12-month progression-free survival rate (PFS%), and secondary endpoints included the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS).
Between September 16, 2020, and November 11, 2021, a total of 21 patients were enrolled in the study. The median follow-up was 36.8 months (ranging from 33.2 to 40.4 months), and all 21 patients were included in the evaluation. The PFS% at 12-month was 81% (95% confidence interval (CI): 64.1-97.9%), the median PFS was 26 months (95% CI: 16.5-35.5) and the ORR reached 85.7%, with an average reduction of the target lesions of 48.2%. Among patients with CNS metastasis, the ORR was 92.9% (13/14), and for TP53 co-mutation patients, the ORR was 86.6% (12/14). Grade 3 adverse events were observed in 4 patients (19.2%), and no grade 4 or 5 adverse events reported.
The combination of aumolertinib and bevacizumab in patients with advanced EGFRm NSCLC achieved the study's primary endpoint. This study indeed extended PFS compared with previous literature, and it was deemed safe and tolerable.
奥莫替尼是一种新型第三代表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI），在中国，其对未经治疗的具有EGFR敏感突变（EGFRm）的非小细胞肺癌（NSCLC）患者的疗效和安全性已得到证实。CTONG1509、JO25567和NEJ026研究证实了第一代EGFR-TKIs与贝伐单抗联合使用可改善无进展生存期（PFS），然而，第三代EGFR-TKIs联合贝伐单抗的效果仍存在争议。本研究旨在探讨奥莫替尼联合贝伐单抗治疗未经治疗的EGFRm晚期NSCLC的疗效和安全性。
我们对奥莫替尼联合贝伐单抗治疗晚期EGFRm NSCLC进行了一项II期单臂前瞻性临床试验。治疗持续至疾病进展、出现不可接受的毒性或患者撤回同意。研究根据性别、吸烟史、分期、EGFR突变状态和中枢神经系统（CNS）转移进行分层。主要终点是12个月无进展生存率（PFS%），次要终点包括客观缓解率（ORR）、总生存期（OS）和无进展生存期（PFS）。
在2020年9月16日至2021年11月11日期间，共有21例患者纳入研究。中位随访时间为36.8个月（范围为33.2至40.4个月），所有21例患者均纳入评估。12个月时的PFS%为81%（95%置信区间（CI）：64.1-97.9%），中位PFS为26个月（95%CI：16.5-35.5），ORR达到85.7%，靶病灶平均缩小48.2%。在有CNS转移的患者中，ORR为92.9%（13/14），对于TP53共突变患者，ORR为86.6%（12/14）。4例患者（19.2%）观察到3级不良事件，未报告4级或5级不良事件。
奥莫替尼与贝伐单抗联合治疗晚期EGFRm NSCLC患者达到了研究的主要终点。与以往文献相比，本研究确实延长了PFS，且被认为是安全且可耐受的。
