Gerber David E, Mayer Melissa, Gagan Jeffrey, von Itzstein Mitchell S
Department of Internal Medicine, Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas.
Division of Hematology and Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
JTO Clin Res Rep. 2022 Feb 15;3(3):100291. doi: 10.1016/j.jtocrr.2022.100291. eCollection 2022 Mar.
L747P mutations occur rarely, with limited preclinical research and case reports suggesting resistance to osimertinib.
An 84-year-old white male with remote smoking history presented with bilateral pulmonary nodules and multiple subcentimeter enhancing brain lesions 2 years after receiving stereotactic radiation therapy for a left upper lobe lung adenocarcinoma. After two computed tomography-guided biopsies yielded inadequate tissue and cell-free DNA analysis identified no actionable alterations, surgical biopsy results revealed an L747P mutation. Limited case reports and preclinical data suggested that this rare mutation may be resistant to the third-generation EGFR inhibitor osimertinib and recommended use of second-generation EGFR inhibitors. Because the patient had low disease burden and there were concerns on tolerability of second-generation EGFR inhibitors, the patient was initiated on osimertinib. Treatment was well-tolerated and follow-up imaging results revealed thoracic and intracranial response to therapy, which has been sustained 6 months after treatment initiation.
Despite predicted and previously reported resistance, osimertinib may have durable efficacy against rare L747P mutations. Persistent attempts to acquire material for tumor genomic analysis may yield results critically important to clinical management.
L747P突变很少见，临床前研究有限，病例报告显示对奥希替尼耐药。
主要关注点、重要临床发现、主要诊断、干预措施、结果：一名有既往吸烟史的84岁白人男性，在接受立体定向放射治疗左上叶肺腺癌2年后，出现双侧肺结节和多个小于1厘米的强化脑病变。两次计算机断层扫描引导下的活检获取的组织不足，游离DNA分析未发现可操作的改变，手术活检结果显示存在L747P突变。有限的病例报告和临床前数据表明，这种罕见突变可能对第三代表皮生长因子受体（EGFR）抑制剂奥希替尼耐药，并建议使用第二代EGFR抑制剂。由于患者疾病负担低，且担心第二代EGFR抑制剂的耐受性，该患者开始使用奥希替尼治疗。治疗耐受性良好，后续影像学检查结果显示胸部和颅内对治疗有反应，治疗开始6个月后仍持续存在。
尽管有预测和先前报道的耐药情况，但奥希替尼可能对罕见的L747P突变具有持久疗效。持续尝试获取肿瘤基因组分析材料可能会得出对临床管理至关重要的结果。
