Zhu Pengcheng, Li Zhitong, Sun Yuxiang, Liu Tongyan, Yin Rong
Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital & Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China.
The Fourth Clinical College of Nanjing Medical University, Nanjing, China.
Cancer Sci. 2025 Mar;116(3):581-591. doi: 10.1111/cas.16428. Epub 2024 Dec 13.
Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), especially third-generation TKIs, have significantly improved the progression-free survival and overall survival of non-small cell lung cancer (NSCLC) patients with EGFR mutation, TKI resistance is inevitable for most patients. Over the past few years, immune checkpoint inhibitors (ICIs) have significantly improved the survival for EGFR-wild type NSCLC patients. However, no significantly improved benefits were observed with ICI monotherapy in EGFR-mutated patients. EGFR-mutated NSCLC shows more heterogeneity in tumor mutational burden (TMB), programmed cell death-ligand 1 (PD-L1), and immune microenvironment characteristics. Whether ICIs are suitable for EGFR-mutated NSCLC patients remains to be elucidated. In this review, we summarized clinical trials of ICIs or combined therapy in EGFR-mutated NSCLC patients. We further discussed the factors determining the efficacy of ICIs in EGFR-mutated NSCLC patients, the mutation subtypes and microenvironment characteristics of potential responders. More importantly, we provided insights into areas worth further investigation in the future.
尽管表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs），尤其是第三代TKIs，显著提高了表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）患者的无进展生存期和总生存期，但大多数患者不可避免地会出现TKI耐药。在过去几年中，免疫检查点抑制剂（ICIs）显著提高了EGFR野生型NSCLC患者的生存率。然而，在EGFR突变患者中，ICI单药治疗未观察到显著改善的疗效。EGFR突变的NSCLC在肿瘤突变负荷（TMB）、程序性细胞死亡配体1（PD-L1）和免疫微环境特征方面表现出更多的异质性。ICI是否适用于EGFR突变的NSCLC患者仍有待阐明。在这篇综述中，我们总结了ICI或联合治疗EGFR突变NSCLC患者的临床试验。我们进一步讨论了决定ICI在EGFR突变NSCLC患者中疗效的因素、潜在应答者的突变亚型和微环境特征。更重要的是，我们对未来值得进一步研究的领域提供了见解。
