Jia Jingquan, Morse Michael A, Nagy Rebecca J, Lanman Richard B, Strickler John H
Department of Medicine, Duke University Medical Center, Durham, NC, United States.
Guardant Health, Inc., Redwood City, CA, United States.
Front Oncol. 2018 Aug 28;8:305. doi: 10.3389/fonc.2018.00305. eCollection 2018.
amplification is rare in treatment-naïve metastatic colorectal cancer (CRC) tumors, but can emerge as a mechanism of resistance to anti-EGFR therapies. Preclinical and clinical data suggest that patients with amplified tumors benefit from MET-targeted therapy. Cabozantinib is an inhibitor of multiple tyrosine kinases, included c-MET. Panitumumab is an inhibitor of EGFR. This report describes a patient with , and wild-type metastatic CRC who experienced disease progression on all standard chemotherapy and anti-EGFR antibody therapy. The patient was enrolled in a clinical trial evaluating the combination of cabozantinib plus panitumumab. After only 6 weeks of treatment, the patient experienced a significant anti-tumor response. Although tumor tissue was negative for amplification, molecular profiling of cell-free DNA (cfDNA) revealed amplification. This case represents the first report showing the activity of cabozantinib in combination with panitumumab in a patient with metastatic CRC, and suggests that amplification in cfDNA may be a biomarker of response. A clinical trial targeting amplified metastatic CRC is currently underway.
在未经治疗的转移性结直肠癌（CRC）肿瘤中，扩增很少见，但可作为对抗表皮生长因子受体（EGFR）治疗耐药的一种机制出现。临床前和临床数据表明，肿瘤扩增的患者可从MET靶向治疗中获益。卡博替尼是一种多种酪氨酸激酶的抑制剂，包括c-MET。帕尼单抗是一种EGFR抑制剂。本报告描述了一名具有野生型转移性CRC且在所有标准化疗和抗EGFR抗体治疗中均出现疾病进展的患者。该患者参加了一项评估卡博替尼联合帕尼单抗的临床试验。仅治疗6周后，患者就出现了显著的抗肿瘤反应。尽管肿瘤组织的扩增为阴性，但游离DNA（cfDNA）的分子谱分析显示有扩增。该病例是首例显示卡博替尼联合帕尼单抗在转移性CRC患者中活性的报告，并表明cfDNA中的扩增可能是反应的生物标志物。目前正在进行一项针对扩增的转移性CRC的临床试验。
