For patients diagnosed with advanced HER2-altered non-small cell lung cancer (NSCLC), the current standard of care is represented by a platinum-pemetrexed-based chemotherapy, eventually in combination with immunotherapy. Different pan-HER tyrosine kinase inhibitors have been evaluated in limited phase II trials, yielding generally unsatisfactory outcomes, although certain genotypes demonstrated some clinical benefit. Conversely, antibody-drug conjugates (ADCs) targeting HER2, particularly trastuzumab-deruxtecan, have shown promising results against HER2-mutant disease, including a great intracranial activity in patients with brain metastasis. Based on the results obtained from DESTINY-Lung01 and DESTINY-Lung02 trials, trastuzumab deruxtecan received regulatory approval as the first targeted therapy for pre-treated, HER2-mutant, advanced NSCLC patients. More recently, the Food and Drug Administration (FDA) granted the accelerated approval of trastuzumab deruxtecan for advanced, pre-treated HER2-positive solid tumours with no other treatment options. In this scenario, emerging evidence is increasingly pointing towards the exploration of combination regimens with synergistic effects in the advanced disease. In this review, we provide a detailed summary of current approaches and emerging strategies in the management of HER2-altered NSCLC, also focusing on unmet needs, including the treatment of patients with brain metastases.
对于确诊为晚期HER2变异非小细胞肺癌（NSCLC）的患者，当前标准治疗方案为以铂类-培美曲塞为基础的化疗，必要时可联合免疫治疗。多种泛HER酪氨酸激酶抑制剂已在有限的II期试验中进行评估，总体疗效不尽如人意，但特定基因型患者显示出一定临床获益。相比之下，靶向HER2的抗体偶联药物（ADCs），尤其是德曲妥珠单抗，在治疗HER2突变型疾病中展现出良好前景，对脑转移患者亦表现出显著的颅内活性。基于DESTINY-Lung01和DESTINY-Lung02试验结果，德曲妥珠单抗已获监管部门批准，成为首个用于经治HER2突变晚期NSCLC患者的靶向疗法。近期，美国食品药品监督管理局（FDA）加速批准德曲妥珠单抗用于治疗无其他治疗选择的晚期经治HER2阳性实体瘤。在此背景下，新兴证据日益指向探索具有协同效应的联合治疗方案在晚期疾病中的应用。本综述详细总结了当前HER2变异NSCLC的治疗策略与新兴方案，并着重探讨了尚未满足的临床需求，包括脑转移患者的治疗问题。
HER2-Altered Non-Small Cell Lung Cancer: A Journey from Current Approaches to Emerging Strategies
肿瘤(癌症)患者之家