Osimertinib-Associated Cardiomyopathy In Patients With Non-Small Cell Lung Cancer: A Case Series.
Osimertinib-Associated Cardiomyopathy In Patients With Non-Small Cell Lung Cancer: A Case Series.
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DOI：
10.1016/j.jaccao.2023.07.006
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发表时间：
2023-12
影响因子：
11.1
通讯作者：
Zhu, Han
中科院分区：
文献类型：
--
作者：
Franquiz, Miguel J.;Waliany, Sarah;Xu, Audrey Yingwei;Hnatiuk, Anna;Wu, Sean M.;Cheng, Paul;Wakelee, Heather A.;Neal, Joel;Witteles, Ronald;Zhu, Han
表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）可使用EGFR酪氨酸激酶抑制剂（TKI）进行有效治疗。临床试验已证明EGFR-TKI奥希替尼可改善生存率，并增加心力衰竭的发生率，同时治疗期间射血分数降低。1本研究的目的是描述在开始奥希替尼治疗后发生心肌病的患者的表型。这是由斯坦福大学机构审查委员会批准的单中心回顾性病例系列，利用斯坦福大学医学研究数据库（STARR）进行队列筛选，然后进行手动图表审查并从电子健康记录中提取研究变量。分析的患者为：1）2016年1月1日至2022年6月1日期间，针对STARR数据库中任何阶段的EGFR突变型NSCLC处方了奥希替尼（N ¼ 862）; 2）有急性收缩性心力衰竭的ICD-10代码，并且左心室射血分数（LVEF）新降低至少10%，绝对值为# 50%（有或无症状）;和3）由治疗临床医生确定奥希替尼为新发心肌病的疑似原因。手动审查了所有符合这些标准的患者（N ¼ 23）的记录，6例患者因心力衰竭的其他病因（心律失常[n ¼ 2]、急性冠状动脉综合征[n ¼ 3]和心包填塞[n ¼ 1]）而被排除。在其余17例患者中，奥希替尼被确定为心力衰竭的可能或很可能原因。患者的中位年龄为72岁（Q1-Q3：65-79岁），17例患者中有12例（70.6%）为女性，17例患者中有11例为亚洲人（64.7%），体重指数的中位数为20.7 kg/m2（Q1-Q3：18.7-23.9 kg/m2）。十（58.8%）至少有3个心脏危险因素，包括：15/17（88.2%）伴高血压，10/17高脂血症8例（58.8%）（47.1%）房颤，5/17（29.4%）患有冠状动脉疾病，3/17（17.6%）既存心肌病，3/17 17例患者中有2例（17.6%）有糖尿病史，2例（11.8%）有吸烟史，1例（5.9%）有慢性肾脏疾病，1例（5.9%）有卒中。16例（94.1%）在奥希替尼治疗开始时患有IV期NSCLC; 7/17例（41.2%）既往接受过细胞毒性化疗，主要是铂类药物和抗代谢药物。3例患者（17.6%）既往接受过贝伐珠单抗治疗。未接受蒽环类或抗人表皮生长因子受体（HER 2）药物治疗。所有患者均进行了心肌病其他病因的诊断性检测，但未提示其他病因。心脏病专家对14例（82.4%）患者进行了评价，奥希替尼被认为是所有患者LVEF降低的病因。3例患者（17.6%）由其他亚专科医生（肺病学、肿瘤学）治疗，奥希替尼被认为是所有原因。使用Naranjo药物不良反应评估工具，我们确定奥希替尼为17例患者中13例（76.5%）心肌病的“可能”原因，17例患者中4例（23.5%）为“很可能”原因。2在17例患者中，有9例（52.9%）进行了超声心动图检查，以检查新的或恶化的症状;在17例患者中的其余8例（47.1%）中，在开始奥希替尼治疗后，进行了超声心动图检查，作为筛查措施。LVEF降低的中位幅度为1.22。0（第一至三季度：2014年）。0到32。0），发生在开始奥希替尼治疗后中位4.2个月（Q1-Q3：3.3-9.4个月）。两人患有Takotsubo综合征，这与恶性肿瘤和奥希替尼有关。3 …
Non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations can be effectively treated with EGFR tyrosine kinase inhibitors (TKIs). Clinical trials have demonstrated improved survival with the EGFR-TKI osimertinib, as well as an increased incidence of heart failure with reduced ejection fraction during treatment. 1 The objective of this study was to characterize the patient phenotype of those who develop cardiomyopathy after initiating osimertinib. This was a single-center retrospective case series approved by the institutional review board at Stanford University utilizing the Stanford Medicine Research Data Repository(STARR) for cohort screening, followed by manual chart review and abstraction of study variables from the electronic health record. Patients analyzed were: 1) prescribed osimertinib for EGFR-mutant NSCLC of any stage in the STARR database from January 1, 2016 to June 1, 2022 (N ¼ 862); 2) had an ICD-10 code for acute systolic heart failure and developed a new reduction in the left ventricular ejection fraction (LVEF) of at least 10% to an absolute value of# 50%(with or without symptoms) while taking osimertinib; and 3) were determined by treating clinicians to have osimertinib as the suspected cause of new cardiomyopathy. The records of all patients meeting these criteria (N ¼ 23) were manually reviewed, and 6 patients were excluded due to alternative etiologies of heart failure (arrhythmia [n ¼ 2], acute coronary syndrome [n ¼ 3], and cardiac tamponade [n ¼ 1]). In the remaining 17 patients, osimertinib was determined to be the possible or probable cause of heart failure. The median age of the patients was 72 years (Q1-Q3: 65-79 years), 12 of 17 patients (70.6%) were female, 11 of 17 patients were Asian (64.7%), and the median of the body mass index was 20.7 kg/m2 (Q1-Q3: 18.7-23.9 kg/m2). Ten (58.8%) had at least 3 cardiac risk factors including: 15 of 17 (88.2%) with hypertension, 10 of 17 (58.8%) with hyperlipidemia, 8 of 17 (47.1%) with atrial fibrillation, 5 of 17 (29.4%) with coronary artery disease, 3 of 17 (17.6%) with pre-existing cardiomyopathy, 3 of 17 (17.6%) with diabetes, 2 of 17 (11.8%) with history of smoking, 1 of 17 (5.9%) with chronic kidney disease, and 1 of 17 (5.9%) with stroke. Sixteen (94.1%) had Stage IV NSCLC at the time of osimertinib initiation; 7 of 17 (41.2%) were previously treated with cytotoxic chemotherapy, predominantly platinum agents and antimetabolites. Three patients (17.6%) had previous bevacizumab treatment. None were treated with anthracyclines or anti-human epidermal growth factor receptor (HER2) agents. All patients had diagnostic testing for alternative causes of cardiomyopathy that did not suggest another etiology. Fourteen (82.4%) were evaluated by cardiologists, with osimertinib attributed as the etiology of LVEF reduction in all. Three patients (17.6%) were managed by other subspecialists (pulmonology, oncology), with osimertinib attributed as the cause in all. Using the Naranjo Adverse Drug Reaction assessment tool, we determined osimertinib as the “possible” cause of cardiomyopathy in 13 of 17 patients (76.5%), and “probable” in 4 of 17 patients (23.5%). 2In 9 of 17 patients (52.9%), an echocardiogram was obtained for workup of new or worsening symptoms; in the remaining 8 of 17 patients (47.1%), an echocardiogram was obtained as a screening measure after starting osimertinib. The median magnitude of LVEF reduction was À22. 0 (Q1-Q3: À14. 0 to À32. 0), occurring at a median of 4.2 months (Q1-Q3: 3.3-9.4 months) after starting osimertinib. Two had Takotsubo syndrome, which has been associated with malignancy and osimertinib. 3 …