人表皮生长因子受体2(HER2)具有酪氨酸激酶活性,参与细胞生长,分化和迁移,和生存。它的改变,主要包括突变,扩增,和过表达与不良预后相关,并且是非小细胞肺癌(NSCLC)的主要驱动因素之一。一些临床试验一直在研究HER2改变的NSCLC的治疗方法,包括常规化疗,程序性死亡1(PD-1)抑制剂,酪氨酸激酶抑制剂(TKIs)和抗体-药物偶联物(ADC),然而,结果要么令人失望,要么令人鼓舞,但不一致。曲妥珠单抗deruxtecan(T-DXd)最近被食品和药物管理局批准为治疗HER2突变型NSCLC的第一个靶向药物。有效筛查患者是临床应用HER2靶向药物如TKIs和ADC的关键。现在有各种各样的测试方法,包括聚合酶链反应(PCR),下一代测序(NGS),荧光原位杂交(FISH),免疫组织化学(IHC),等。每种方法都有其优缺点,应合理分配给适当的患者进行诊断和指导治疗决策。为了帮助标准化临床工作流程,我们的专家组就HER2改变的非小细胞肺癌的临床治疗达成共识,专注于诊断和治疗策略。
Human epidermal growth factor receptor 2 (HER2) possesses tyrosine kinase activity and participates in cell growth, differentiation and migration, and survival. Its alterations, mainly including mutations, amplifications, and overexpression are associated with poor prognosis and are one of the major drivers in non-small cell lung cancer (NSCLC). Several clinical trials had been investigating on the treatments of HER2-altered NSCLC, including conventional chemotherapy, programmed death 1 (PD-1) inhibitors, tyrosine kinase inhibitors (TKIs) and antibody-drug conjugates (ADCs), however, the results were either disappointing or encouraging, but inconsistent. Trastuzumab deruxtecan (T-DXd) was recently approved by the Food and Drug Administration as the first targeted agent for treating HER2-mutant NSCLC. Effective screening of patients is the key to the clinical application of HER2-targeted agents such as TKIs and ADCs. Various testing methods are nowadays available, including polymerase chain reaction (PCR), next-generation sequencing (NGS), fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), etc. Each method has its pros and cons and should be reasonably assigned to appropriate patients for diagnosis and guiding treatment decisions. To help standardize the clinical workflow, our expert group reached a
consensus on the clinical management of HER2-altered NSCLC, focusing on the diagnosis and treatment strategies.