Department of Thoracic Oncology, Osaka Prefectural Hospital Organization, Osaka International Cancer Institute, Otemae 3-1-69, Chuo-ku, Osaka City, Osaka, 541-8567, Japan.
Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwanoha 6-5-1, Kashiwa City, Chiba, 277-8577, Japan.
Invest New Drugs. 2021 Feb;39(1):232-236. doi: 10.1007/s10637-020-00966-7. Epub 2020 Jun 18.
Exon 18 mutations account for only 3.6% of EGFR mutations, and tumors with exon 18 mutations are often unresponsive to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). We present a novel case of a lung adenocarcinoma with an exon 18 mutation resulting in a glycine to serine substitution at position 719 of the EGFR protein. The patient received osimertinib, a third generation EGFR-TKI, as the first-line treatment, but the disease progressed during treatment. Analysis of circulating free DNAs via next generation sequencing revealed TP53 mutations and EGFR and MET amplifications, as well as the exon 18 mutation. On the basis of these results, we administered afatinib, a second-generation TKI, and bevacizumab, a vascular endothelial growth factor inhibitor, as the second-line treatment. The patient's symptoms improved, and this treatment was continued for 12 months. This report suggests that afatinib plus bevacizumab can effectively treat osimertinib-refractory lung tumors with an exon 18 mutation.
外显子 18 突变仅占 EGFR 突变的 3.6%，并且携带外显子 18 突变的肿瘤通常对表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）无反应。我们报告了一例新的肺腺癌，其 EGFR 蛋白的第 719 位的甘氨酸突变为丝氨酸。患者接受奥希替尼（第三代 EGFR-TKI）作为一线治疗，但在治疗过程中疾病进展。通过下一代测序对循环游离 DNA 进行分析显示 TP53 突变和 EGFR 和 MET 扩增以及外显子 18 突变。基于这些结果，我们给予第二代 TKI 阿法替尼和血管内皮生长因子抑制剂贝伐珠单抗作为二线治疗。患者的症状改善，该治疗持续了 12 个月。本报告表明，阿法替尼联合贝伐珠单抗可有效治疗奥希替尼耐药的携带外显子 18 突变的肺肿瘤。
