Shen Qian, Qu Jingjing, Chen Zhen, Zhou Jianying
Department of Respiratory Disease, Thoracic Disease Centre, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Laboratory Medicine and Pathology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Front Oncol. 2021 Dec 2;11:760097. doi: 10.3389/fonc.2021.760097. eCollection 2021.
Advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations has been successfully treated with tyrosine kinase inhibitors (TKIs). However, resistance to osimertinib, a third-generation TKI, can be difficult to overcome in this small subset of patients and is attributed to secondary resistant mutations. Here, we report a case of acquired EGFR L858R/L718Q mutation with advanced NSCLC that resistant to osimertinib, which was successfully overcome using dacomitinib.
A 64-year-old non-smoker woman was diagnosed with stage IV non-small cell lung adenocarcinoma with EGFR L858R mutation and brain metastasis in November 2018. Treatment with gefitinib and gamma knife radiosurgery was started as the first-line treatment. After 7 months, she experienced disease progression with increased primary lung lesions and switched to osimertinib based on an acquired EGFR T790M mutation. After another 4 months, the disease progressed, and she was switched to chemotherapy. During chemotherapy, brain MRI showed an increasing number of parietal lobe metastases. Hence, gamma knife radiosurgery was performed again. After 12 months, the disease progression resumed, and an EGFR L718Q mutation was found on biopsy. The patient was then challenged with dacomitinib, and the disease was partially responsive and under control for 6 months.
Currently, there are no established guidelines for overcoming osimertinib resistance caused by the L718Q mutation. The acquired EGFR L718Q mutation in subsequent resistance to osimertinib could be overcome using dacomitinib, indicating a promising treatment option in the clinic.
携带表皮生长因子受体（EGFR）突变的晚期非小细胞肺癌（NSCLC）已成功用酪氨酸激酶抑制剂（TKIs）治疗。然而，在这一小部分患者中，第三代TKI奥希替尼的耐药性可能难以克服，这归因于继发性耐药突变。在此，我们报告一例晚期NSCLC获得性EGFR L858R/L718Q突变且对奥希替尼耐药的病例，该病例使用达可替尼成功克服了耐药性。
一名64岁不吸烟女性于2018年11月被诊断为IV期非小细胞肺腺癌，伴有EGFR L858R突变和脑转移。开始使用吉非替尼和伽玛刀放射外科作为一线治疗。7个月后，她出现疾病进展，原发性肺部病变增多，并基于获得性EGFR T790M突变改用奥希替尼。又过了4个月，疾病进展，她改用化疗。化疗期间，脑部MRI显示顶叶转移灶数量增加。因此，再次进行了伽玛刀放射外科治疗。12个月后，疾病再次进展，活检发现EGFR L718Q突变。然后该患者接受达可替尼治疗，疾病部分缓解并得到控制6个月。
目前，对于克服由L718Q突变引起的奥希替尼耐药性尚无既定指南。后续对奥希替尼耐药中获得的EGFR L718Q突变可使用达可替尼克服，这表明在临床上是一种有前景的治疗选择。
