Le Jonathan N, Gasho Jordan O, Peony Olivia, Singh Asneh, Silos Katrina D, Kim Sungjin, Nguyen Anthony T, Kamrava Mitchell, Mirhadi Amin, Hakimian Behrooz, Reckamp Karen L, Sankar Kamya, Mak Raymond H, Nikolova Andriana P, Atkins Katelyn M
Department of Medicine, Cedar-Sinai Medical Center, Los Angeles, CA, United States.
Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
Front Cardiovasc Med. 2024 Dec 16;11:1485033. doi: 10.3389/fcvm.2024.1485033. eCollection 2024.
Osimertinib is first-line treatment for epidermal growth factor (EGFR)-mutated non-small cell lung cancer (NSCLC) and has been associated with cardiotoxicity. However, the nature of cardiac remodeling and associated risk factors remains incompletely understood. Retrospective analysis of NSCLC patients with ≥1 echocardiogram post-osimertinib between 2007 and 2022 was performed. The cumulative incidence of grade ≥2 cardiac common terminology criteria for adverse events (CTCAE) was estimated and Fine and Gray regressions performed (non-cardiac death as competing risk). Eighty-five patients [mean [interquartile range, IQR], 68 [60-75] years; 67% female; 12% with pre-existing heart conditions] met inclusion criteria. With a median follow up of 34.7 months, the 2-year cumulative incidence of grade ≥2 and grade ≥3 cardiac events were 19.2% and 8.5%, respectively. There was an increased risk of grade ≥2 cardiac CTCAE with pre-existing arrhythmia [hazard ratio(HR) 3.90, 95%CI, 1.11-13.72; = 0.034] and higher body mass index (HR 1.07, 95%CI, 1.00-1.14; = 0.04). Following osimertinib (vs. baseline), the median QTc was prolonged (451 vs. 437 ms; < 0.001) and LVEF ≤50% was more common (10.6% vs. 5.3%; = .046). Osimertinib treatment was associated with QTc prolongation and reduced LVEF. BMI was identified as a potentially modifiable risk factor for osimertinib-associated cardiotoxicity, worthy of further study.
奥希替尼是表皮生长因子（EGFR）突变的非小细胞肺癌（NSCLC）的一线治疗药物，且与心脏毒性有关。然而，心脏重塑的本质及相关危险因素仍未完全明确。对2007年至2022年间接受奥希替尼治疗后有≥1次超声心动图检查的NSCLC患者进行回顾性分析。估计不良事件通用术语标准（CTCAE）≥2级心脏事件的累积发生率，并进行Fine和Gray回归分析（以非心脏死亡作为竞争风险）。85例患者[平均[四分位间距，IQR]，68[60 - 75]岁；67%为女性；12%有既往心脏病史]符合纳入标准。中位随访34.7个月，≥2级和≥3级心脏事件的2年累积发生率分别为19.2%和8.5%。既往有心律失常的患者发生≥2级心脏CTCAE的风险增加[风险比（HR）3.90，95%置信区间（CI），1.11 - 13.72；P = 0.034]，且体重指数较高时风险也增加（HR 1.07，95%CI，1.00 - 1.14；P = 0.04）。与奥希替尼治疗前（对比基线）相比，中位QTc延长（451对437毫秒；P < 0.001），左心室射血分数（LVEF）≤50%更为常见（10.6%对5.3%；P = 0.046）。奥希替尼治疗与QTc延长和LVEF降低有关。体重指数被确定为奥希替尼相关心脏毒性的一个潜在可改变的危险因素，值得进一步研究。
