在非小细胞肺癌（NSCLC）患有人表皮生长因子受体2（HER2）突变的情况下，由于传统的全HER酪氨酸激酶抑制剂（TKIs）和HER2靶向单克隆抗体的微弱疗效，在过去十年中，化疗仍然是标准治疗方法。近年来，新型选择性HER2 TKIs已经为接受过预处理的HER2突变患者开发出来。特别是，吡咯替尼已经显示出适度的疗效和可管理的安全性，现正进一步评估其单药或与其他现有疗法联合使用；相比之下，佐伊替尼虽然显示了有前途的初步结果，但高毒性率阻碍了随后的研究。值得注意的是，Trastuzumab deruxtecan（T-DXd，DS-8201）取得了重大突破，是所有抗HER2药物中最具鼓舞人心的疗效数据（响应率为55％，中位无进展生存期为8.2个月，中位总生存期为17.8个月）。这无疑是一个显着的进展，T-DXd毫无疑问是该病的关键药物。关于T-DXd的未来发展是有利的，包括从单药治疗转向联合策略，改进结构设计以优化抗肿瘤活性并尽量减少毒性，确定潜在的耐药机制并开发克服它们的治疗策略。还需要应对其他几个挑战，例如抗HER2药物的颅内活性和治疗的最佳排序。在这里，我们总结了最近在NSCLC中针对HER2突变的治疗进展，并强调了这些患者人群的未来展望。版权所有©2023年作者。由Elsevier Ltd. 发布。保留所有权利。

In non-small cell lung cancer (NSCLC) with human epidermal growth factor receptor 2 (HER2) alterations, chemotherapy remains the standard treatment over a decade, due to the minor efficacy of traditional pan-HER tyrosine kinase inhibitors (TKIs) and HER2-targeted monoclonal antibodies. In recent years, novel selective HER2 TKIs have been developed for pretreated HER2-mutant patients. In particular, pyrotinib has shown moderate efficacy as well as a manageable safety profile, and it is now being further evaluated as monotherapy or combined with other existing therapies; by contrast, while poziotinib has demonstrated promising preliminary results, the high rates of toxicity has hampered subsequent studies. Most notably, trastuzumab deruxtecan (T-DXd, DS-8201) has led to a significant breakthrough, with the most encouraging efficacy data (response rate of 55 %, median progression-free survival of 8.2 months and median overall survival of 17.8 months) among all the anti-HER2 agents. This is certainly remarkable progress, and T-DXd is undoubtedly the key drug for the treatment of this disease. Future developments regarding T-DXd are favourable, including shifting from monotherapy to combination strategies, improving structural design to optimise antitumour activity and minimise toxicity, identifying the potential resistance mechanisms and developing therapeutic strategies to overcome them. Several other challenges need to be addressed, such as the intracranial activity of anti-HER2 agents and the optimal sequencing of therapies. Here, we summarise recent therapeutic advances in targeting HER2 alterations in NSCLC and highlight the future perspectives of these patient populations.Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.