Nützinger Jorn, Bum Lee Jii, Li Low Jia, Ling Chia Puey, Talisa Wijaya Silvana, Chul Cho Byoung, Min Lim Sun, Soo Ross A
Department of Haematology-Oncology, National University Cancer Institute, Singapore.
Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
Lung Cancer. 2023 Dec;186:107385. doi: 10.1016/j.lungcan.2023.107385. Epub 2023 Sep 28.
HER2 mutations, which account for 2-4% of non-small cell lung cancer (NSCLC), are distinct molecular alterations identified via next generation sequencing (NGS). Previously, treatment outcomes in HER2-mutant metastatic NSCLC were dismal, showing limited clinical benefit with platinum-based chemotherapy with or without immunotherapy. In contrast to HER2-altered breast and gastric cancer, HER2-mutant NSCLC does not benefit from HER2 targeting agents such as trastuzumab or TDM1. HER2 mutations are also inherently different from HER2 overexpression and amplification. Currently, trastuzumab deruxtecan, a HER2 targeting antibody drug conjugate (ADC) is the first and only approved treatment option for patients with HER2-mutant metastatic NSCLC after failure with standard treatment. In this review, we summarized the biology of HER2 and detection of HER2 overexpression, amplification and mutations, as well as general landscape of landmark and ongoing clinical trials encompassing from chemotherapy to targeted agents, including tyrosine kinase inhibitors (TKIs), ADCs and investigational agents.
HER2突变占非小细胞肺癌（NSCLC）的2%-4%，是通过下一代测序（NGS）鉴定出的独特分子改变。此前，HER2突变的转移性NSCLC的治疗结果令人沮丧，在接受含或不含免疫治疗的铂类化疗时，临床获益有限。与HER2改变的乳腺癌和胃癌不同，HER2突变的NSCLC无法从曲妥珠单抗或TDM1等HER2靶向药物中获益。HER2突变在本质上也与HER2过表达和扩增不同。目前，曲妥珠单抗德鲁替康，一种HER2靶向抗体药物偶联物（ADC），是HER2突变的转移性NSCLC患者在标准治疗失败后的首个也是唯一获批的治疗选择。在这篇综述中，我们总结了HER2的生物学特性以及HER2过表达、扩增和突变的检测方法，以及从化疗到靶向药物（包括酪氨酸激酶抑制剂（TKIs）、ADC和研究性药物）的标志性和正在进行的临床试验的总体情况。
