奥希替尼治疗 EGFR T790M 阳性晚期肺腺癌患者出现重度血小板减少1例
1 上海市胸科医院/上海交通大学附属胸科医院呼吸内科，上海 200030
报告1例晚期肺腺癌合并骨转移病例，经多线治疗后，血癌胚抗原(carcinoembryonic antigen，CEA)进行性增高，服用一代表皮生长因子受体抑制剂(epidermal growth factor receptor tyrosine kinase inhibitor，EGFR-TKI)易瑞沙(Iressa)约1年出现耐药，血液检测(易瑞沙治疗>16个月)及二次组织活检(易瑞沙治疗>22个月)均证实存在T790M突变。2018年7月首次口服三代EGFR-TKI奥希替尼80 mg，1次/d，约20 d，血小板即出现明显降低，停药后血小板有所恢复，继续应用奥希替尼80 mg，1次/d，再次出现血小板减少，期间血CEA有下降且病灶稳定，提示奥希替尼治疗有效，但出现血小板降低无法耐受。至2018年11月停用奥希替尼。至2019年3月病情明显进展，临床诊断“脑膜转移”后，再次应用奥希替尼80 mg，1次/d，仅3 d，血小板由97×109/L降至37×109/L，停用奥希替尼血小板回升至68×109/L，2019年4月4日考虑奥希替尼减量至40 mg，1次/d口服，但2019年4月8日复测血小板仅为21×109/L，再次停用奥希替尼口服。回顾本病例，如果能够在肿瘤负荷相对较小(易瑞沙治疗约1年)时，及时转换为奥希替尼治疗，预计患者能够取得相对更好的结局；提示真实世界中治疗方案的制订受到多种因素的影响，及时进行二次活检了解患者的基因状态也越来越重要。
Severe thrombocytopenia induced by treatment of osimertinib in a patient with advanced lung adenocarcinoma with EGFR T790M mutation
CorrespondingAuthor: SHI Chunlei
This work was supported by the Basic Research Cultivation Project of Shanghai Chest Hospital (2019YNJCM14), China.
We report a case of lung adenocarcinoma with bone metastasis. After multiple line treatments, the blood carcinoembryonic antigen (CEA) increased gradually. The first-generation EGFR-TKI showed resistance in about one year. EGFR T790M mutation was confirmed by Blood test (after 16+ months of Iressa treatment) and second tissue biopsy (after 22+ months of Iressa treatment). In July 2018, after the first use of Osimertinib (80 mg, 1 time/d), platelet decreased significantly, platelet recovered after withdrawal of Osimertinib, thrombocytopenia continued to occur again after Osimertinib treatment. During this period, blood CEA decreased and the lesion was stable, suggesting that Osimertinib treatment was effective, but platelet reduction could not be tolerated until 2018. Osimertinib was discontinued in November 2018. By March 2019, the patient’s condition had progressed significantly and the clinical diagnosis was “meningeal metastasis”, the platelet count dropped from 97×109/L to 37×109/L only three days after the application of osimertinib (80 mg, 1 time/d). The platelet count increased to 68×109/L after the discontinuation of Osimertinib. The reduction of osimertinib to 40 mg (1 time/d) was considered in April 4, 2019, but the platelet count was only 21×109/L in April 8, 2019, and the oral dose of osimertinib was discontinued again. Looking back at this case, if we can switch to osimertinib treatment in time when the tumor load is relatively small (about 1 year of Iressa treatment), we can expect better outcomes. This also reflects that the formulation of treatment plan in the real world is affected by many factors, and it is more and more important to conduct a timely second biopsy to understand the genetic status of patients.
osimertinib; lung adenocarcinoma; severe thrombocytopenia; EGFR T790M mutation