酪氨酸激酶抑制剂 (TKI) 作为一线药物的批准彻底改变了被诊断为携带靶向突变的晚期非小细胞肺癌 (NSCLC) 患者的治疗方法，与化疗相比，显着增加了总生存 (OS) 获益。然而，这些药物的功效在病程的某个时刻不可避免地会减弱，这要么是由于细胞耐药机制，要么是由于药代动力学受影响，例如中枢神经系统渗透性低。本文的目的是回顾关于在晚期 NSCLC 中联合使用 EGFR（表皮生长因子）或 ALK（间变性淋巴瘤激酶）特异性 TKI 和放疗 (RT) 的现有证据，以尝试延迟或克服 TKI -耐药性，从而延长患者从给定的靶向治疗中获益的时间段。目前，将放疗与 EGFR 或 ALK-TKI 联合治疗晚期肿瘤驱动基因突变 NSCLC 已显示出相当有前景的结果，在 PFS 和 OS 方面，使得延长 TKI 衍生的获益成为可能，且毒性通常可耐受。需要进一步的研究来确认观察到的疗效并澄清可能的安全问题以及适当的治疗顺序和目标量，特别是在新一代 TKI 快速发展的时代。版权所有 © 2024 Elsevier B.V. 保留所有权利。

The approval of tyrosine kinase inhibitors (TKIs) as first-line agents has revolutionised treatment of patients diagnosed with advanced non-small cell lung cancer (NSCLC) harboring targetable mutations, adding substantial overall survival (OS) benefit, compared to chemotherapy. However, the efficacy of these agents is inevitably diminished at a point in the disease course, either because of cellular resistance-mechanisms or due to affected pharmacokinetics, like low-central nervous system penetration. The aim of this article is to review existing evidence on the combined use of EGFR (epidermal growth factor)- or ALK (anaplastic lymphoma kinase)-specific TKIs and radiotherapy (RT) in advanced NSCLC setting, as an attempt to delay or overcome TKI-resistance and thus, to expand the time period during which patients derive benefit from a given line of targeted therapy. At present, combining RT with EGFR- or ALK-TKIs in the management of advanced, oncodriver-mutated NSCLC has shown quite promising results, with regards to PFS and OS, rendering prolongation of the TKI-derived benefit feasible, with generally tolerable toxicity. Future studies to confirm the observed efficacy and clarify possible safety issues as well as the appropriate treatment sequence and target volumes are needed, especially in the rapidly-evolving era of newer-generation TKIs.Copyright © 2024 Elsevier B.V. All rights reserved.