MET抑制剂联合EGFR/ALK酪氨酸激酶抑制剂在经治EGFR突变/ALK重排且MET过表达的非小细胞肺癌患者中的有益前景：一项回顾性队列研究
Promising benefits of MET inhibition combined with EGFR/ALK tyrosine kinase inhibitor in heavily treated non-small cell lung cancer patients with EGFR-mutant/ALK rearrangement and MET overexpression: a retrospective cohort study.
作者
作者单位
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
- Department of Pathology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
- Department of Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
摘要
中文
表皮生长因子受体（EGFR）或间变性淋巴瘤激酶（ALK）酪氨酸激酶抑制剂（TKI）耐药在EGFR突变或ALK重排的非小细胞肺癌（NSCLC）患者中仍然常见。间质上皮转化（MET）过表达在获得性耐药中起关键作用。然而，同时靶向EGFR/ALK驱动因素和MET的联合酪氨酸激酶抑制的真实世界证据有限。本研究旨在评估该人群中EGFR/ALK和MET联合抑制的疗效和安全性。我们进行了一项单中心回顾性队列研究，纳入对既往EGFR/ALK靶向治疗产生耐药并表现出MET过表达的EGFR突变或ALK重排NSCLC患者。符合条件的患者接受EGFR/ALK TKI和MET抑制剂联合治疗。使用实体瘤疗效评价标准1.1版（RECIST v1.1）评估治疗反应，采用Kaplan-Meier法估计无进展生存期（PFS）和总生存期（OS）。共分析23例患者数据。客观缓解率（ORR）为69.6%，其中16例部分缓解，6例疾病稳定。中位PFS为6.9个月。高水平MET过表达（定义为免疫组化（IHC）3+）与MET IHC 2+相比具有更高的缓解率。治疗总体耐受性良好，大多数不良事件为低级别且可控。EGFR/ALK和MET双重抑制在MET过表达的EGFR/ALK突变NSCLC患者中显示出有前景的抗肿瘤活性和可接受的安全性，为克服获得性耐药提供了可行策略。
English
Resistance to epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) remains common in patients with EGFR-mutant or ALK rearrangement non-small cell lung cancer (NSCLC). Mesenchymal-epithelial transition (MET) overexpression plays a key role in acquired resistance. However, real-world evidence on combined tyrosine kinase inhibition targeting both EGFR/ALK drivers and MET is limited. This study aimed to evaluate the efficacy and safety of combined EGFR/ALK and MET inhibition in this population. We performed a single-center, retrospective cohort study of NSCLC patients with EGFR mutations or ALK rearrangements who developed resistance to prior EGFR/ALK-targeted therapies and exhibited MET overexpression. Eligible patients received combined treatment with EGFR/ALK TKIs and MET inhibitors. Treatment responses were assessed using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), and progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Data of a total of 23 patients were analyzed. The objective response rate (ORR) was 69.6%, with partial responses in 16 patients and stable disease in 6. Median PFS was 6.9 months. High-level MET overexpression, defined as immunohistochemistry (IHC) 3+, was associated with a higher response rate compared to MET IHC 2+. The treatment was generally well-tolerated, with most adverse events being low-grade and manageable. Dual inhibition of EGFR/ALK and MET offers promising antitumor activity with an acceptable safety profile in EGFR/ALK-mutant NSCLC patients with MET overexpression, providing a viable strategy for overcoming acquired resistance.
分类与指标
- 研究类型
- 临床研究
- 病种
- 肺癌
- JCR 分区
- Q2
- 影响因子
- 3.4
- 新锐分区
- 3区