Case report: NSCLC with pulmonary embolism after treatment with almonertinib

Zelu Han, Lingshuang Liu, Yi Jiang, Xintong Gao
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Abstract

Almonertinib is the first independently developed third generation epidermal growth factor receptor tyrosine kinase inhibitors in China. It can be used not only for epidermal growth factor receptor (EGFR) sensitive mutation patients but also for T790M (+) resistant patients, and has better safety and survivability compared to the first and second generation EGFR-TKIs. The previous literature and case studies have reported significant treatment-related adverse reactions in non-small cell lung cancers patients treated with almonertinib, including elevated blood creatine phosphatase, prolonged cardiac QT interval, altered myocardial contractility, interstitial lung disease, eye disease, and hematological events. But there are few individual reports of pulmonary embolism events. A 55-year-old female with no history of smoking visited a local hospital with mild cough and lower sacrococcygeal pain without obvious cause. She was diagnosed with right lung adenocarcinoma with multiple bone metastases (T2bN1M1c, stage IVB) after image and histological examination, with EGFR 21 exon L858R sensitive mutation. She initially underwent surgical treatment due to the discovery of a sacral tumor, and the pathology of the surgery indicated metastatic lung adenocarcinoma. Genetic testing results showed EGFR 21 exon L858R sensitive mutation. Combined with positron emission tomography/computed tomography imaging results and sacral tumor surgical pathology results, it was considered that the patient had lung adenocarcinoma with multiple bone metastases. Treatment plan: targeted treatment with almonertinib which is the third-generation EGFR-TKIs. After only 1 month of targeted treatment, chest enhanced computed tomography revealed pulmonary embolism imaging, combined with coagulation indicators, considering pulmonary embolism. As the thromboembolic site is located at the end of the pulmonary artery branch and imaging shows that tumor lesions are stable. Consider continuing targeted treatment with almonertinib and adjuvant oral anticoagulant therapy with rivaroxaban for treatment. Two months later, the patient’s condition was followed up and it was found that the imaging manifestations of pulmonary embolism disappeared, but the coagulation indicators remained in a hypercoagulable state. The patient’s treatment plan remained unchanged, and the patient was hospitalized for follow-up every 6 to 8 weeks to closely observe changes in the condition. There are many reasons for the occurrence of hypercoagulable blood in tumor patients, and there are very few reports of treatment-related pulmonary embolism events in patients who are treated with almonertinib targeted therapy. It is particularly important to determine whether the hypercoagulable blood in such patients is related to targeted therapy drugs in clinical practice, as this will affect the clinical benefits of patients in epidermal growth factor receptor tyrosine kinase inhibitors treatment and the clinical indicators which need to pay more attention in follow-up observation, to avoid serious pulmonary embolism events and thus affect the patient’s survival status and quality of life.
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病例报告:使用阿莫替尼治疗 NSCLC 后出现肺栓塞
阿莫替尼是中国首个自主研发的第三代表皮生长因子受体酪氨酸激酶抑制剂。它不仅可用于表皮生长因子受体(EGFR)敏感突变患者,也可用于T790M(+)耐药患者,与第一代和第二代EGFR-TKIs相比,具有更好的安全性和生存率。既往文献和病例研究报道了阿莫替尼治疗非小细胞肺癌患者的显著治疗相关不良反应,包括血肌酸磷酸酶升高、心脏QT间期延长、心肌收缩力改变、间质性肺病、眼病和血液学事件。但关于肺栓塞事件的个别报道很少。 一名无吸烟史的 55 岁女性因轻微咳嗽和无明显诱因的下骶尾部疼痛到当地医院就诊。 经影像和组织学检查,她被诊断为右肺腺癌伴多发性骨转移(T2bN1M1c,IVB 期),表皮生长因子受体 21 外显子 L858R 敏感突变。 她最初因发现骶骨肿瘤而接受手术治疗,手术病理结果显示为转移性肺腺癌。基因检测结果显示表皮生长因子受体 21 外显子 L858R 敏感突变。结合正电子发射断层扫描/计算机断层扫描成像结果和骶骨肿瘤手术病理结果,考虑患者为肺腺癌伴多发性骨转移。治疗方案:使用第三代表皮生长因子受体抑制剂(EGFR-TKIs)阿莫奈替尼进行靶向治疗。靶向治疗仅1个月后,胸部增强计算机断层扫描显示肺栓塞影像,结合凝血指标,考虑肺栓塞。由于血栓栓塞部位位于肺动脉分支末端,且造影显示肿瘤病灶稳定。考虑继续使用阿莫替尼进行靶向治疗,并使用利伐沙班进行辅助口服抗凝治疗。 两个月后,对患者病情进行随访,发现肺栓塞影像学表现消失,但凝血指标仍处于高凝状态。患者的治疗方案保持不变,每 6 至 8 周住院随访一次,密切观察病情变化。 肿瘤患者发生高凝状态的原因有很多,而在接受阿莫替尼靶向治疗的患者中,与治疗相关的肺栓塞事件的报道非常少。在临床实践中,判断此类患者的高凝血是否与靶向治疗药物有关尤为重要,因为这将影响患者在表皮生长因子受体酪氨酸激酶抑制剂治疗中的临床获益,也是后续观察中需要更加关注的临床指标,避免发生严重的肺栓塞事件,进而影响患者的生存状态和生活质量。
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