Miao Xu, Liu Yuan, Li Xiaoqin, Zhao Rong
Department of Pharmacy, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
Adverse Drug Reaction Monitoring Department, Food and Drug Supervision and Inspection Center in Zhenjiang, Zhenjiang, Jiangsu, China.
Front Pharmacol. 2025 Aug 29;16:1652750. doi: 10.3389/fphar.2025.1652750. eCollection 2025.
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have emerged as a mainstay for patients diagnosed with non-small cell lung cancer (NSCLC). However, interstitial lung disease (ILD), potentially fatal, may develop in certain patients during EGFR-TKI therapy. We aimed to characterize EGFR-TKI-associated ILD and examine the risk factors.
Adverse event (AE) reports from the FDA Adverse Event Reporting System were retrieved from Q1 2004 to Q1 2024. AEs were identified at the preferred term level using the Standardized MedDRA Query. Four disproportionality analyses were conducted to quantify the signal of ILD associated with EGFR-TKIs. The risk of ILD was subsequently analyzed using multifactorial logistic regression.
A total of 20,195 EGFR-TKI-related AE reports were analyzed, with 660 cases linked to ILD. osimertinib accounted for the most ILD reports (156), while dacomitinib showed the highest reporting odds. Subgroup analyses revealed distinct pulmonary toxicity profiles across the different EGFR-TKIs. Erlotinib exhibited the longest median time to onset. Older age, concomitant dyslipidemia, and concomitant use of lansoprazole significantly increased the risk.
ILD risk is elevated in EGFR-TKI-treated NSCLC patients, particularly with older age, comorbidities, and lansoprazole use. Clinicians should consider these factors to reduce ILD incidence.
表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）已成为诊断为非小细胞肺癌（NSCLC）患者的主要治疗手段。然而，在某些患者接受EGFR-TKI治疗期间可能会发生潜在致命的间质性肺病（ILD）。我们旨在描述与EGFR-TKI相关的ILD特征并研究其危险因素。
从2004年第一季度至2024年第一季度检索美国食品药品监督管理局不良事件报告系统中的不良事件（AE）报告。使用标准化医学术语词典查询在首选术语级别识别AE。进行了四项不成比例分析以量化与EGFR-TKIs相关的ILD信号。随后使用多因素逻辑回归分析ILD的风险。
共分析了20195份与EGFR-TKI相关的AE报告，其中660例与ILD有关。奥希替尼的ILD报告最多（156例），而达可替尼的报告比值最高。亚组分析揭示了不同EGFR-TKIs的独特肺部毒性特征。厄洛替尼的中位发病时间最长。年龄较大、合并血脂异常以及同时使用兰索拉唑会显著增加风险。
在接受EGFR-TKI治疗的NSCLC患者中，ILD风险升高，尤其是在年龄较大、合并症以及使用兰索拉唑的情况下。临床医生应考虑这些因素以降低ILD的发生率。
