Wang Chongkai, Fakih Marwan
1Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, California.
J Natl Compr Canc Netw. 2021 Jun 30;19(6):670-674. doi: 10.6004/jnccn.2021.7023.
Dual HER2-targeted therapy has been associated with clinical responses and prolonged progression-free survival and overall survival in RAS-wild type HER2-amplified colorectal cancer (CRC). However, no clinical benefits have been reported in patients with CRC with HER2 mutations. Activated HER2 mutations have been largely deemed resistant to trastuzumab and to dual HER2 targeting. This report describes a patient with metastatic CRC with concurrent HER2 amplification and a HER2 S310F mutation, which is an active mutation located in the extracellular dimerization domain of HER2. Treatment with trastuzumab + lapatinib resulted in an excellent response that lasted for 10 months. Upon disease progression, treatment with the antibody-drug conjugate trastuzumab-deruxtecan resulted in a short-lived response. This is the first case report of successful HER2 targeting in metastatic CRC with concurrent HER2 amplification and a HER2 S310F mutation.
双重HER2靶向治疗已与RAS野生型HER2扩增型结直肠癌（CRC）的临床反应、延长无进展生存期和总生存期相关。然而，尚未有关于HER2突变型CRC患者临床获益的报道。激活的HER2突变在很大程度上被认为对曲妥珠单抗和双重HER2靶向治疗耐药。本报告描述了一名患有转移性CRC的患者，该患者同时存在HER2扩增和HER2 S310F突变，这是一种位于HER2细胞外二聚化结构域的激活突变。曲妥珠单抗+拉帕替尼治疗产生了持续10个月的良好反应。疾病进展后，使用抗体-药物偶联物曲妥珠单抗-德曲妥珠单抗治疗产生了短暂反应。这是首例关于同时存在HER2扩增和HER2 S310F突变的转移性CRC成功进行HER2靶向治疗的病例报告。
