ALK融合非小细胞肺癌患者真实世界中接受洛拉替尼治疗相关不良心血管事件

Cardiovascular adverse events associated with lorlatinib treatment in ALK-positive non-small cell lung cancer patients in the real world

摘要:

目的]观察新型第三代间变性淋巴瘤激酶(ALK)酪氨酸激酶抑制剂洛拉替尼治疗非小细胞肺癌(NSCLC)患者过程中,主要不良心血管事件的发生情况及药物干预的效果。 [方法]选取2018年3月—2025年1月期间,广东省人民医院收治的92例ALK融合阳性NSCLC患者,分析洛拉替尼治疗后不良心血管事件的发生率及近期与远期效应,评估他汀类药物对治疗引起的高脂血症干预效果。 [结果]本研究纳入92例ALK融合阳性NSCLC患者。洛拉替尼治疗后,高脂血症是最常见的不良心血管事件(59例,64.1%),其中1级、2级和3级事件分别发生15例(25.4%)、33例(55.9%)和11例(18.6%),无4级事件发生。与洛拉替尼治疗相关的不良心血管事件的发生多集中于治疗早期(0～6个月内),尤其是高脂血症和窦性心动过速。在接受治疗后12个月时,心包积液和血栓等不良心血管事件依然有一定发生率,提示这些不良心血管事件可能在较长时间内对患者健康产生一定影响。他汀类药物干预可显著改善血脂异常,经药物干预患者总胆固醇(TC)、甘油三酯(TG)及低密度脂蛋白(LDL)水平较单药组分别显著下降了35.25%、64.15%和35.71%(P＜0.05)。 [结论]洛拉替尼治疗ALK融合阳性NSCLC患者具有良好的疗效,但其引起的不良心血管事件,特别是高脂血症和窦性心动过速,仍需在临床中引起关注。药物干预,尤其是使用他汀类药物,可有效控制血脂水平,从而降低心血管风险并改善患者的治疗预后。因此,建议在临床实践中加强对高风险患者的早期筛查与密切监测,尤其是在治疗的初期阶段,确保及时干预,并对长期治疗中的不良反应进行持续关注。

Abstract:

Aim To observe the incidence of major adverse cardiovascular events (ACE) during treatment with lorlatinib, a novel third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), in patients with non-small cell lung cancer (NSCLC), and evaluate the effect of pharmacological interventions. Methods A total of 92 ALK-positive NSCLC patients admitted to Guangdong Provincial People's Hospital between March 2018 and January 2025 were selected. The study analyzed the incidence of ACE following lorlatinib treatment, including the immediate and long-term effects, and evaluated the effectiveness of statin intervention for hyperlipidemia induced by the treatment. Results A total of 92 ALK-positive NSCLC patients were included in the study. Hyperlipidemia was the most common ACE, observed in 59 patients (64.1%), with 1st, 2nd, and 3rd grade events occurring in 15 patients (25.4%), 33 patients (55.9%), and 11 patients (18.6%), respectively. No grade 4 events were reported. The CVAEs related to lorlatinib were concentrated in the early phase of treatment (0~6 months), particularly hyperlipidemia and sinus tachycardia. After 12 months of treatment, pericardial effusion and thrombosis still showed a certain incidence, suggesting that these cardiovascular events may have a long-term impact on patients' health. Statin intervention significantly mitigated dyslipidemia. Compared with the lorlatinib monotherapy group, the levels of total cholesterol (TC), triglycerides (TG), and low density lipoprotein (LDL) in the intervention group were significantly reduced by 35.25%, 64.15%, and 35.71%, respectively (P＜0.05). Conclusion Lorlatinib treatment for ALK-positive NSCLC patients demonstrated good efficacy, but its ACEs, especially hyperlipidemia and sinus tachycardia, require attention in clinical practice. Pharmacological interventions, particularly statins, can effectively control lipid levels, thereby reducing cardiovascular risks and improving patients' prognosis. Therefore, it is recommended to enhance early screening and close monitoring for high-risk patients in clinical practice, especially during the early stages of treatment, to ensure timely intervention and continuous attention to long-term adverse effects.